Next-Generation Algae, Volume 2 Applications in Medicine and The Pharmaceutical Industry

Next-Generation Algae
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Next-Generation Algae
Volume II: Applications in Medicine

and the Pharmaceutical Industry
Edited by
Charles Oluwaseun Adetunji
Julius Kola Oloke
Naveen Dwivedi
Sabeela Beevi Ummalyma
Shubha Dwivedi
Daniel Ingo Hefft
and
Juliana Bunmi Adetunji
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ISBN 978-1-119-85728-0
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10 9 8 7 6 5 4 3 2 1
Contents
Preface xv
1 Discovery of Novel and Biologically Active Compounds
from Algae 1
M. Singh, N. Gupta, P. Gupta, Doli, P. Mishra and A. Yadav
1.1 Introduction 2
1.2 Microalgae-Derived Natural Products 3
1.3 Bioprospecting for New Algae 4
1.4 Therapeutically Essential Natural Products 6
1.5 Screening for Bioactive Constituents 7
1.6 Extraction Methods 9
1.7 Biosynthesis and Biological Activities 11
1.7.1 Antibacterial Action 15
1.7.2 Antifungal Action 17
1.7.3 Anti-Inflammatory Action 18
1.7.4 Antiprotozoal Action 19
1.7.5 Antioxidant Action 20
1.7.6 Antineoplastic (Anticancer) Action 21
1.7.7 Antiviral Action 24
1.7.8 Anticoagulant Action 25
1.7.9 Immunosuppressive Action 25
1.8 Conclusion 26
References 27
2 Bioactive Compounds Synthesized by Algae: Current
Development and Prospects as Biomedical Application
in the Pharmaceutical Industry 41
Preeti Mishra, Namrata Gupta, Monika Singh
and Deeksha Tiwari
2.1 Introduction 42
2.2 Algal-Sourced Compounds of Medical Interest 43
v
vi Contents
2.3 Microalgae with Potential for Obtaining

Bioactive Compounds 44
2.3.1 Spirulina 46
2.3.2 Chlorella 47
2.3.3 Nostoc 49
2.3.4 Dunaliella 50
2.4 Bioactive Compounds from Cyanobacteria 51
2.5 Secondary Metabolites from Microalgae 55
2.5.1 Carotenoids 55
2.5.1.1 β-Carotene 55
2.5.1.2 Astaxanthin 57
2.5.1.3 Zeaxanthin and Lutein 58
2.5.1.4 Violaxanthin 59
2.5.1.5 Fucoxanthin 59
2.5.2 Polyunsaturated Fatty Acids 60
2.5.3 Proteins and Polypeptides 61
2.6 Biomass of Microalgae 62
2.6.1 Biomass Production 62
2.6.1.1 Cultivation 62
2.6.1.2 Harvesting 63
2.6.1.3 Biomass Dehydration 64
2.6.1.4 Extraction of Bioactive Compounds 66
2.7 Pharmaceutical Applications of Microalgae 66
2.8 Conclusion 71
References 72
3 Bioactive Compounds Derived from Microalgae
Showing Diverse Medicinal Activities 77
D. Tiwari, P. Mishra and N. Gupta
3.1 Introduction 78
3.2 Microalgae with Anti-Inflammatory Activity 81
3.3 Microalgae with Immunomodulatory Activity 82
3.4 Microalgae Anticancer Activity 85
3.5 Potential of Microalgae in Quality Enhancement
of Natural Products 87
3.5.1 Pharmaceutical Industry 87
3.5.2 Cosmetics and Personal Care 87
3.5.3 Food Industry 88
References 90
Contents vii
4 Application of Astaxanthin and Carotenoids Derived

from Algae for the Production of Nutraceuticals,
Pharmaceuticals, Additives, Food Supplement and Feed 95
Abiola Folakemi Olaniran, Joshua Opeyemi Folorunsho,
Bolanle Adenike Akinsanola, Abiola Ezekiel Taiwo,
Yetunde Mary Iranloye, Clinton Emeka Okonkwo
and Omorefosa Osarenkhoe Osemwegie
4.1 Carotenoids and Its Characteristics 96
4.1.1 Sources of Carotenoids 97
4.1.2 Production/Extraction of Carotenoids 99
4.2 Astaxanthin and Its Characteristics 102
4.2.1 Production/Extraction of Astaxanthin 103
4.2.2 Historical Perspective of Consumption of Alga
as Food and Utilization in the Food Industry 104
4.3 Application/Utilization of Astaxanthin and Carotenoids
in Different Sectors 105
4.3.1 Nutraceuticals 108
4.3.2 Food Additives, Supplements and Feed Formulation 110
4.3.3 Alga as a Potential Source of Astaxanthin
and Food Supplement 111
4.3.4 Technological Application of Algae as Origins
of Supplements and Bioactive Mixtures in Healthier
Food Varieties and Drinks 112
4.3.5 Enriching Dairy Products with Algae 114
4.3.6 Algae as a Potential Healthy Protein and Fat Source 115
4.4 Future Perspective 117
References 118
5 Production of Polyunsaturated Fatty Acids (PUFAs)
and Their Biomedical Application 125
Olorunsola Adeyomoye, Olugbemi T. Olaniyan
and Charles O. Adetunji
5.1 Introduction 125
5.2 Polyunsaturated Fatty Acids 126
5.3 Production of Polyunsaturated Fatty Acids 127
5.4 Nanomedicine-Based Formulations Containing
Polyunsaturated Fatty Acids 128
5.5 Biological and Medical Application of Polyunsaturated
Fatty Acids 129
5.6 Metabolism of Polyunsaturated Fatty Acid 131
viii Contents
5.7 Challenges and Issues of Production and Use

of Polyunsaturated Fatty Acids 132
5.8 Conclusion 133
References 133
6 Utilization of Algae and Their Anti-Proliferative
and Anti-Inflammatory Activities 139
Olorunsola Adeyomoye, Olugbemi T. Olaniyan
and Charles O. Adetunji
6.2 Physiology and Biochemistry of Algae 141
6.3 Algae Biocomposites 141
6.4 Techniques and Methods Involved in the Production
of Algae Biocomposites 143
6.5 Antiproliferative Activities of Algae 144
6.6 Anti-Inflammatory Activities of Algae 144
6.7 Potential Health Benefits of Algae Biocomposites 146
6.8 Challenges and Issues Related to Algae Biocomposites Use 147
6.9 Conclusion 147
References 148
7 Natural Compounds of Algae Origin with Potential
Anticarcinogenic Benefits 153
Adewale Omowumi Oyeronke, Asowata-Ayodele Abiola Mojisola,
Akomolafe Seun Funmilola and Adetunji Juliana Bunmi
7.2 Progression, Predisposing Factors and Treatment of Cancer 156
7.2.1 Cancer Progression 156
7.2.2 Predisposing Factors to Cancer 157
7.2.3 Treatment of Cancer 157
7.3 Features of Microalgae 157
7.4 Sources of Microalgae 158
7.5 Fractions of Microalgae Species with Anticancer Properties 158
7.5.1 Carotenoid-Rich Extracts of Chlorella Species 158
7.5.2 Chaetoceros Calcitrans Ethyl Acetate
and Ethanol Extracts 159
7.5.3 Amphidinium Carterae Organic Fractions 159
7.5.4 Methanolic Extracts from Amphidinium Carterae,
Prorocentrum Rhathymum, Symbiodinium sp.,
Contents ix
Coolia Malayensis, Ostreopsis Ovata, Amphidinium

Operculatum, and Heterocapsa Psammophila 160
7.5.5 Skeletonema Marinoi Hydrophobic Fraction 160
7.5.6 Canadian Marine Microalgal Pool Aqueous Extract 160
7.5.7 Chlorella Sorokiniana Aqueous Extract 161
7.6 Compounds with Anticarcinogenic Activities Isolated
from Marine Microalgae 161
7.6.1 Polysaccharides 161
7.6.2 Phycocyanin 163
7.6.3 Chlorophyll 163
7.6.4 Polyunsaturated Aldehydes (PUAs) 164
7.6.5 Violaxanthin 164
7.6.6 Eicosapentaenoic Acid (EPA) 165
7.6.7 Stigmasterol 166
7.6.8 Fucoxanthin 166
7.6.9 Nonyl 8-Acetoxy-6-Methyloctanoate (NAMO) 167
7.6.10 Monogalactosyl Glycerols 168
7.6.11 Other Active Compounds from Microalgae
with Anticarcinogenic Activities 168
7.7 Conclusion and Recommendation 168
References 169
8 Current Research on Algal-Derived Sulfated Polysaccharides
and Their Antiulcer Bioactivities 177
Abiola Mojisola Asowata-Ayodele, Adewale Omowumi Oyeronke,
Akomolafe Seun Funmilola and Adetunji Juliana Bunmi
8.1.1 Symptoms of Peptic Ulcer Disease 179
8.2 Treatment Using Synthetic Medicines 181
8.3 Natural Products Used in the Treatment of Peptic Ulcer 183
8.4 Antiulcer Products Developed from Algae 184
8.4.1 Phycocolloids 186
8.4.2 Fucoidan 188
8.4.3 Ulvans 189
8.4.4 Laminaran 190
8.4.5 Xylan and Porphyran 191
8.5 Conclusion 193
References 193
x Contents
9 Pharmacological and Antioxidant Attributes of Significant

Bioactives Constituents Derived from Algae 197
Juliana Bunmi Adetunji, Abigail Omotayo Agbolade,
Omowumi Oyeronke Adewale, Ikechukwu P. Ejidike,
Charles Oluwaseun Adetunji and Isreal Olu Oyewole
9.1.1 Brown Algae 198
9.1.1.1 Fucoidan and Its Bioactivity 198
9.1.1.2 Benefits Derived from Fucoidan 200
9.1.1.3 Laminarin 202
9.1.1.4 Fucosterol 204
9.1.1.5 Saccharides 204
9.1.1.6 Phlorotannins 206
9.1.1.7 Dieckol 207
9.1.2 Red Algae 207
9.1.2.1 D-Isofloridoside 207
9.1.2.2 Phycoerythrin 208
9.1.3 Blue-Green Algae 209
9.1.3.1 Phycocyanin and Phycocyanobilin 209
9.1.4 Other Potential Applications of Algae 215
9.1.4.1 Antioxidant and Anti-Tyrosine Capabilities 215
9.2 Conclusion 216
References 216
10 Utilization of Pharmacologically Relevant Compounds
Derived from Algae for Effective Management
of Diverse Diseases 223
Olulope Olufemi Ajayi
10.2 Algae in the Management of Some Diseases 225
10.2.1 Cancer 225
10.2.2 Inflammatory Bowel Disease 226
10.2.3 Osteoarthritis 227
10.2.4 Gastric Ulcers 227
10.2.5 Neurodegenerative Diseases 227
10.2.6 Diabetes Mellitus 228
10.2.7 Hypertension 228
10.2.8 Atherosclerosis 229
10.2.9 Kidney and Liver Diseases 230
10.2.10 Skin Diseases/Disorders 230
10.2.11 Uterine Leiomyomas 231
Contents xi
10.2.12 Obesity 232

10.2.13 Tuberculosis 234
10.2.14 Asthma 235
10.2.15 Hepatitis 236
10.3 Xanthophylls 236
10.3.1 Astaxanthin 236
10.3.3 Lutein and Zeaxanthin 237
10.3.4 Beta-Cryptoxanthin 237
10.3.5 Siphonaxanthin 238
10.3.6 Saproxanthin and Myxol 238
10.4 Alga Diterpenes 238
10.5 Conclusion 239
References 239
11 Application of Algae in Wound Healing 251
Ebenezer I. O. Ajayi, Johnson O. Oladele
and Abraham O. Nkumah
11.1.1 Current Trends in the Design of Wound Dressings 253
11.2 Brown Seaweed Polysaccharides 256
11.2.1 Fucoidan 257
11.2.2 Alginate 258
11.2.3 Carrageenan 259
11.2.4 Red Seaweed Polysaccharides 260
11.2.5 Green Seaweed Polysaccharides 260
11.3 Mechanisms Underpinning the Wound Healing Effects
of Algae 261
11.3.1 Hemostatic Activity 263
11.3.2 Immunomodulatory and Anti-Inflammatory
Effects 264
11.3.3 Antioxidant Activity 267
11.3.4 Antifungal Activity 269
11.3.5 Antibacterial Properties 269
11.3.6 Wound-Healing Property of Algae
and Cyanobacteria 271
11.4 Conclusion 274
References 274
xii Contents
12 Application of Nanotechnology for the Bioengineering

of Useful Metabolites Derived from Algae and Their
Multifaceted Applications 285
Charles Oluwaseun Adetunji, Olugbemi T. Olaniyan,
Inobeme Abel, Ruth Ebunoluwa Bodunrinde,
Nyejirime Young Wike, Wadzani Dauda Palnam,
Juliana Bunmi Adetunji, Phebean Ononsen Ozolua,
Arshad Farid, Shakira Ghazanfar, Olorunsola Adeyomoye,
Muhammad Akram, Chibuzor Victory Chukwu
and Mohammed Bello Yerima
12.2 Various Types of Nanoparticles Derived from Algae 287
12.3 Nanoparticles from Algae and the Key Role They Play
in the Medical and Pharmaceutical Sectors 295
12.3.1 Anticancer Activity 298
12.4 Algae-Derived Nanoparticles and Their Key Role in the
Cosmetics Industry 302
12.4.1 Algae-Derived Nanoparticles as Moisturizer 302
12.4.2 Algae-Derived Nanoparticles as Skin Sensitizing
and Thickening Agents 302
12.4.3 Algae-Derived Nanoparticles as Anti-Aging
Agents 303
12.4.4 Algae-Derived Nanoparticles as Antioxidant
Agent 303
12.5 Algae-Derived Nanoparticles as Antibacterial Agent 303
12.6 Algae-Derived Nanoparticles as Antifungal Agent 306
12.7 Algae-Derived Nanoparticles as Antiviral Agent 306
12.8 Conclusion 307
References 307
13 Discovery of Novel Compounds of Pharmaceutical
Significance Derived from Algae 321
Charles Oluwaseun Adetunji, Muhammad Akram,
Fahad Said Khan, Olugbemi T. Olaniyan,
Babatunde Oluwafemi Adetuyi, Inobeme Abel,
Ruth Ebunoluwa Bodunrinde, Juliana Bunmi Adetunji,
Phebean Ononsen Ozolua, Nyejirime Young Wike,
Wadzani Dauda Palnam, Arshad Farid, Shakira Ghazanfar,
Olorunsola Adeyomoye, Chibuzor Victory Chukwu
and Mohammed Bello Yerima
Contents xiii
13.2 Bioactive Compounds 323

13.3 Pharmacological Significance of Algae 324
13.3.1 Antioxidative Activity 324
13.3.2 Antihypertensive Activity 325
13.3.3 Anticoagulant Activity 326
13.3.4 Antiproliferation Activities 326
13.3.5 Immune-Stimulant Activity 327
13.3.6 Cholesterol-Lowering Activity 328
13.3.7 Anti-Inflammatory Activity 329
13.3.8 Anticancer Activity 329
13.3.9 Cancer Prevention Agent 330
13.3.10 Antidiabetic 330
13.3.11 Different Biomedical Activities 331
13.4 Research Results on Well-Studied Algal Strains 332
13.5 Conclusion and Future Recommendations 334
References 334
14 Applications of Algae in the Production of Single-Cell
Proteins and Pigments with High Relevance in Industry 343
Juliana Bunmi Adetunji, Omowumi Oyeronke Adewale,
Charles Oluwaseun Adetunji and Isreal Olu Oyewole
14.2 Microalgae-Derived Single Cell Protein (SCP) 345
14.2.1 Dunaliella 346
14.3 Applications of SCP in Diets 347
14.4 Pigments Derived from Algae 348
14.4.1 Astaxanthin 348
14.4.3 Carotenoids 349
14.5 Conclusion 349
References 349
Index 353
Preface
The application of both micro and macroalgae has been recognized as a

next-generation biotechnological tool with the potential to mitigate vari-
ous challenges faced by humankind globally, particularly in catering to the
needs of an ever-increasing population. This companion volume includes
valuable information on nanoparticle synthesis derived from algae and
microalgae, as well as their diverse uses and applications in the production
of products for pathogen diagnostics, pharmacological properties, and dif-
ferent drugs/medicines for human health. Algae has numerous medical
attributes that could serve as a permanent replacement to all the challenges
associated with synthetic drugs, such as high level of resistance, low effec-
tiveness, and high cost. In recent years, there has been a significant shift in
focus toward the application of algae, owing to its numerous applications
in several sectors. Algae is a valuable resource for not only energy and food,
but also conservation, environmental bioremediation, pharmacologically
active substances, agriculture, new industrially important bio-products,
and nutraceuticals.
This book explains how the application of algae could help to resolve
diverse human health challenges through the use of nutritional supple-
ments, therapeutic proteins, vaccines, and algae-derived drugs. It also
provides great detail about the biological activities of some natural drugs
derived from algae, such as anticancer, antimicrobial, antiviral, antiulcer,
antiinflamatory, antihyperlipidermia, antithrombic agents, anticoagulants,
cardioverscular, antitumour, immunomdularory, and various antibiotics.
Also, it describes the use of algae-derived antioxidants in the management
of several health concerns such as inflammations, chronic disorders, and
cardiovascular diseases.
This second volume places special emphasis on the discovery of novel
and biologically active compounds from algae. It covers a wide range of
applications, including the use of astaxanthin and carotenoids derived
from algae for the production of nutraceuticals, pharmaceuticals, addi-
tives, food supplements, and feed. The book also discusses the production
xv
xvi Preface
of polyunsaturated fatty acids (PUFAs) and its biomedical applications,

recent advancements in the research of sulfated polysaccharides from algal
origin, and its antiulcer bioactivities. Other topics include the application
of algae in wound healing, the use of nanotechnology for the bioengi-
neering of useful metabolites derived from algae and their multifaceted
applications, and the production of single-cell proteins and pigments with
high relevance in industry. This book targets a diverse audience, including
global leaders, industrialists, pharmaceutical and food industry profes-
sionals, innovators, policy makers, educators, researchers, and undergrad-
uate and postgraduate students in various interdisciplinary fields such as
medicine, pharmaceuticals, and biotechnology. The information contained
in this book will be invaluable to anyone seeking to explore the poten-
tial applications of algae in various fields and to discover new biologically
active compounds derived from algae for use in medicine, pharmaceuti-
cals, and other related industries.
I want to express my deepest appreciation to all the contributors
who have dedicated their time and efforts to make this book a success.
Furthermore, I want thank my coeditors for their effort and dedication
during this project. Moreover, I wish to gratefully acknowledge the sug-
gestions, help, and support of Martin Scrivener and others from Scrivener
Publishing.
Charles Oluwaseun Adetunji

(Ph.D, AAS affiliate MNYA; MBSN; MNSM, MNBGN)
Dean Faculty of Science, Edo State University, Uzairue, Nigeria
March 2023
1
Discovery of Novel and Biologically
Active Compounds from Algae
M. Singh1*, N. Gupta2, P. Gupta3, Doli1, P. Mishra1 and A. Yadav1
1
Faculty of Pharmacy, RBS Engineering Technical Campus, Bichpuri, Agra, India
2
Faculty of Engineering & Technology, RBS Engineering Technical Campus,
Bichpuri, Agra, India
3
Department of Chemistry, Faculty of Engineering and Technology, SRM Institute
of Science and Technology, Modinagar, Ghaziabad, Uttar Pradesh, India
Abstract
The identification of new therapeutically active constituents from algae is gen-
erating growing attention due to the unique makeup of these organisms and the
potential for widespread industrial use of these constituents. Recent study has con-
centrated on algae, which have a novel biochemical proclivity and a diverse variety
of possible commercial uses, as a provider of novel biologically active constituents.
The growing number of researchers are becoming interested in identifying novel
physiologically active chemicals from algae, owing to its unique composition and
the potential for vast commercial uses. It is very essential to identify the organ-
isms of those species that produce bioactive secondary metabolites that could be
a potential source for new drug development. A variety of constituents, such as
carbohydrates, minerals, oil, proteins along with polyunsaturated fatty acids, are
found in algae preparations. Additionally, biologically active constituents such
as antioxidants (tocopherols or vitamin E), vitamin C and pigments (like phy-
cobilins, carotenoids and chlorophylls) are found in algae preparations. These
biologically active compounds possess different therapeutic properties, such as
antimicrobial (antibacterial, antiviral, antifungal), antineoplastic, antioxidative
and anti-inflammatory properties. They also have the potential to be used as food
by humans. Algae have been discovered to be a significant source of physiologi-
cally active chemicals that may be used in a variety of goods for animals, plants,
cosmetics, and medicines, among other things.
*Corresponding author: [email protected]

Charles Oluwaseun Adetunji, Julius Kola Oloke, Naveen Dwivedi, Sabeela Beevi Ummalyma,
Shubha Dwivedi, Daniel Ingo Hefft and Juliana Bunmi Adetunji (eds.) Next-Generation Algae: Volume II:
Applications in Medicine and the Pharmaceutical Industry, (1–40) © 2023 Scrivener Publishing LLC
1
2 Next-Generation Algae: Volume II
Keywords: Algae, biologically active compounds, therapeutic activities
1.1 Introduction
Water occupies almost 70% of Earth’s surface. Therefore, it is a tremendous
resource for the identification of novel/unique compounds with potential
therapeutic uses. Over the last several decades, a vast variety of new chem-
icals obtained from marine creatures with pharmaceutically therapeutic
benefits have been discovered. Because of this, marine resources are con-
sidered a promising source of new therapeutically active chemicals not
only for the creation of active pharmaceutical ingredients but also for the
development of food items [1].
The marine environment has a diverse range of fauna (sea hares, fishes,
soft corals, sponges, nudibranchs, tunicates, sea slugs, bryozoans, echi-
noderms, shells, along with prawns) and flora (microorganisms such as
micro/macroalgae, cyano- and actinobacteria, bacteria, fungi, halophytes).
Among the most remarkable characteristics of marine life is the close
connection that exists between different groups of creatures in order to
enable them to adapt to the harsh and tough ocean circumstances that
are significantly different than those that exist in a given ecosystem [2].
Phytoplankton (microalgae) have received tremendous interest nowadays
because they are seen as a continuous raw material for producing a range
of bioactive constituents. There are many different types of compounds
that could be utilized in nutraceuticals, pharmaceuticals and as ingredi-
ents in some products like cosmetics. Some of these include terpenoids,
amino acids, phycobiliproteins [3], fatty acids, chlorophylls, steroids,
phenolic compounds, halogenated ketones, vitamins, and carotenes [4].
Photosynthetic microorganisms are known as cyanobacteria. They are
Gram-negative and abundantly distributed throughout the environment.
In various types of industries, including biofuel, nutrition, agriculture, and
medicines, etc., they have a huge spectrum of biotechnological applica-
tions to offer [5].
Micro- and macroalgae (seaweeds), which make up the majority of
marine algae, have possible potential use in different areas of biomedicine
and marine pharmacology. Nowadays, tissue culture technologies are an
up-and-coming area. As significant marine biological resources, algae are
abundant on shallow, coastal, and backwater substrates and may be found
in great quantities in shallow, coastal, and backwater habitats. It has also
been discovered that algae may grow on a variety of solid objects such as
rocks and stones as well as on dead corals, pebbles, and other small objects.
Novel-Biologically Active Compounds Discovery 3
A surprising amount of agar is produced by algae in intertidal and shal-

low water, with a total production of about 6000 tonnes of total agar yield.
Investigations have demonstrated that unrefined and refined compounds
generated from marine algae showed significant antimicrobial action in
vitro against a broad range of both Gram-negative as well as Gram-positive
pathogenic microorganisms and also showed in vivo activity [6]. In addi-
tion to being interesting as research targets, because of their potential ther-
apeutic qualities, the natural significant bioactive chemicals derived from
microalgae are anticipated to be commercialized in the next several years
[3].
In the aquatic environment, marine algae, including dinoflagellates (uni
cellular along with biflagellate organisms) and phytoplankton, are symbi-
otic in corals, seaweeds, and sea anemones, among other things. A wide
variety of seaweeds are divided into four groups: Chlorophyta (means
green algae), Rhodophyta (means Red algae), Phaeophyta (means Brown
algae), and Cyanobacteria (certain filamentous Blue-green algae) [1].
Neoplasm (cancer, carcinoma or malignancy), diabetes, metabolic syn-
drome, obesity, chronic stress, stroke, immunological diseases and chronic
respiratory sickness are all contributing to an increase in global morbidity
and death. Dietary modification along with lifestyle modification are cur-
rently suggested as potential approaches to preventing or treating various
ailments [3]. Furthermore, foods containing bioactive constituents may
have the ability to behave as necessary nutrients. Antibiotics were formerly
considered to be “magic bullets,” but by picking certain bacteria for treat-
ment, they might end up becoming a contributing factor to the spread of
illness [7].
1.2 Microalgae-Derived Natural Products

Microalgae are microorganisms of only one cell in size that flourish in salt
water. It also thrives in freshwater environments. Their diameter or length
ranges from 3 to 10 millimeters, and they are available in a variety of forms
and sizes. Microalgae include both bacterial and eukaryotic species, and
the term “microalgae” applies to both [8]. Cyanobacteria are structurally
comparable to bacteria in terms of their composition. They are classified
as microalgae, however, because of the presence of chlorophyll and other
photosynthesis-related compounds in their composition. Known as green
algae due to the fact that they have the same quantities of chlorophyll-a and
chlorophyll-b as green plants [9, 10], they have been studied extensively.
Microalgae produce biocompounds by utilizing light energy along with

inorganic nutrients (nitrogen, phosphorus, carbon dioxide, and other ele-
ments) and are classified as autotrophic microorganisms. They include
nutrients of great nutritional value, such as proteins, lipids, carbohydrates,
polymers, and pigments, as well as medicinal properties. In recent research,
it has been shown that microalgae may create a vast variety of chemical
constituents (compounds) with diversified biological functions, including
phycobilins, polysaccharides, polyunsaturated fatty acids, proteins, sterols,
carotenoids, and vitamins, among other substances [10].
Phaeophyta, i.e., brown algae, are a well-known commercialized algi-
nate source due to their brown color. Alginates are straight, long chains of
amino acids. They consist of residues of the amino acids. Alginates are usu-
ally observed in toothpastes and ice creams, where they are employed as
thickening agents, foam stabilizers, and preservatives. When taken orally,
a low-density agonic acid gel formed from alginate salts operate as a “raft”
that floats over the stomach content, similar to corresponding gelatine.
As a result, stomach acid is prevented from refluxing into the esophagus.
Therefore, sodium/magnesium salts of agonic acid are included in variety
of compound antacid formulations, such as Favicon (Reckitt & Coleman)
or Alicen (Rorer), among others [11]. There are wide variety of applica-
tions of algae, from biofuel production, in particular bioethanol, macro-
and microalgae fermentation, to enzyme extraction in the paper, textile,
and detergent industries, and laboratory applications [12].
Bioactive constituents are substances that are physiologically active in
the human body and have functional characteristics in the body. Many bio-
logically active compounds that have the possibility of being used as useful
components are being developed and manufactured, including polyphe-
nols, phycocyanins, fatty acids, carotenoids, and other polyunsaturated
compounds.
1.3 Bioprospecting for New Algae

Numerous new compounds were found in marine algae during the previ-
ous six decades, and a vast variety of these chemicals have been shown to
have intriguing biological activities [13]. When it comes to the isolation
of new species, there are numerous obstacles to overcome; the dearth of
information regarding the metabolite demands of growth genus, pH, need
for consumption of certain nutrients (e.g., sulphate, nitrogen sources, and
phosphorus), and other growth parameters, like crop density and tempera-
ture, among others. It is critical to understand the chemical interactions
between strains that have not been thoroughly described or novel strains in
order to maximize their production [3]. In 2009, Ou et al. [14] found that
clinical studies are useful for concentrating efforts on extracting protec-
tive bioactive substances with specific therapeutic properties using various
pharmacological models. The method of developing novel molecules as
therapies, from preclinical validation through FDA clearance, is lengthy,
laborious, and costly. A bioactive molecule with high therapeutic prom-
ise requires preclinical investigations, human clinical trials [14, 15], along
with regulatory process permission from the FDA following post-trial for
commercialization and marketing in the contemporary environment [15].
Keep in mind that not all of the medicines included in the database have
been authorized by the Food and Drug Administration (FDA), but they
are all recognized only after evaluation of biological action. In many other
countries, medications are permitted for clinical use; however, in the United
States, none of them have been approved. Animal and human clinical trials
are conducted in order to evaluate the therapeutic property of the isolated
constituents in various periods of development, using a variety of phar-
macological models to do so [3]. Over 18,000 bioactive compounds have
been identified to date. Despite this, only six drugs derived from marine
sources have been clinically authorized and commercialized. Moreover,
only a few algal isolates have been acknowledged clinically. Brentuximab
vedotin, marketed under the trade name Adcetris, is, for instance, an
antibody-drug combination made from bioactive molecules [16] derived
from an algal source used to treat non-Hodgkin lymphoma [17]. Fucoidan
extracts have anti-aging action on the human body in clinical double-blind
trials [18]. Interestingly, the first antiviral algal component found from
Eucheume/Chondrus, a red edible alga, is iota-carrageenan (Carragelose).
Numerous derivatives of dolastatin have been developed and are being
clinically investigated in EMA tests and by the FDA [19]. These deriva-
tives names are glembatumumab vedotin, depatuxizumab mafodotin, and
pinatuzumab vedotin. It has been revealed in clinical studies that EPA,
coupled with DHA, are essential amino acids from marine macroalgae
that have clinical use [20]. As feed additives and immunological boosters,
Ocean Feed™ from macroalgae and Tasco™ from A. nodosum were already
on the market [21].
There have been several well-publicized incidents in the UK of livestock
and other animals being poisoned as a result of cyanobacteria contamina-
tion in their drinking water. Anabaena flosaquae is a plant that produces
the alkaloid named anatoxin-a, which is a neurotoxin that depolarizes neu-
romuscular blocking and has both nicotinic and muscarinic action [5, 22].
1.4 Therapeutically Essential Natural Products

Marine organisms, which include both animals and plants, are the richest
sources of bioactive constituents, which have a diverse variety of pharma-
cological actions, including free radical scavenging, anticancer, neuro-
protective, analgesic, antimicrobial, and immunomodulatory properties,
among other activities. Underwater drugs provide an alternate source for
meeting the growing need for safe, effective, and low-cost medications,
which is increasing in tandem with the world population’s dramatic rise.
In developed nations, the disease of neoplasm (cancer) is among the most
prevalent causes of mortality, whereas communicable infections are the
main cause of mortality in impoverished (developing) nations. Despite the
significant advances in neoplasm or tumor therapy that have occurred over
the past three decades, there is still a pressing need for novel medicines in
the field of cancer biology, particularly in the relatively untapped field of
marine anticancer chemicals, to combat cancer [2].
Chlorella and Spirulina are the most common microalgae species found
on the market, and they dominate the whole market. The first is a green
microalga that includes microalgae and also macroalgae, part of the broad
phylum of Chlorophyta [12].
Polyketides, alkaloids, cyanopeptides, isoprenoids and other metabo-
lites are among the cyanobacterial natural products classified according
to their metabolic origins. While much of the research was focused on
toxicity, many studies also have revealed that cyanobacteria create chem-
icals of considerable pharmaceutical and biotechnological importance.
Forty percent (40%) of lipopeptides, others are less than 10% (e.g., fatty
acids, amino acids, amides, and macrolides) make up cyanobacterial com-
pounds. Therefore, Cyanobacteria activity is dominated by lip peptides
such as cytotoxic (41%), antitumor (13%), antiviral (4%), and antibiotics
(12%). The remaining 18% of cyanobacterial activity includes antimalarial,
antimitotic, and immunosuppressive agents, herbicides, antifeedant, and
multi-drug resistance reversing agents, among others [23].
Various types of Blue-green algae are available in the market as organic
algae nutraceuticals, as well as a source of pharmacologically import-
ant substances. Examples of such species are Spirulina, Chlorella and
Aphanizomenon flos-aquae. Spirulina sp. is a kind of blue-green algae that
is found in the ocean. Lipids, chlorophyll, protein, carotenoids, miner-
als, vitamins, and vibrant colors are all rich in this plant’s composition.
Moreover, they might contain helpful probiotic components [24]. As
well as other carotenoids, minerals (including Ca and Fe) and B vitamins
(including B12), Spirulina sp. is a wonderful abundant source of potas-

sium, calcium, magnesium, iron, selenium and zinc. As an added bonus,
important component fatty acid is beneficial in potentiating hair and
skin growth, regulating metabolism and maintaining bone health. It also
ensures proper functioning of reproductive system. Numerous minerals
and vitamins have powerful antioxidant activities that assist in the elim-
ination of toxins from the environment and the prevention of diseases.
Cyanobacteria have recently attracted the public’s curiosity due to their
high concentrations of bioactive chemicals and their potential as dietary
supplements. They also serve as a model for organisms belonging to some
very promising categories of organisms in terms of the production of bio-
active chemicals. Scientific evidence demonstrating bioactive chemicals
produced from blue-green algae may show therapeutic promise in the
treatment of illness and health issues in both human clinical trials and ani-
mal clinical studies [1].
Agars as well as carrageenan are generated from species of red algae.
Both the agents are utilized as gelling, thickening, and emulsifying agents,
and are the most significant products obtained from red algal species. Agar
is also utilized as a microbiological culture medium, and agarose, which
is a component of nutrient agar used for microbial growth, is also utilized
in electrophoresis, immunodiffusion, and gel chromatography, among
other applications. It’s also used as a hydrogel in the surgical dressing by
Geistlich, which is another use. A carrageenan implant is a substance used
in the pharmaceutical industry to induce inflammation in models for ani-
mal testing. It may be utilized to evaluate prospective anti-inflammatory
and anti-arthritis medicines to produce edema. According to Blunden
and Gordon [11], the gastrointestinal system of primates does not absorb
high molecular weight carrageenans, and as a result, they are believed to
be acceptable additions for human consumption, given that the molecular
weight is tightly controlled.
1.5 Screening for Bioactive Constituents

Multidisciplinary approaches are needed for the determination of bioac-
tive constituents. The advancement of analytical and molecular methods
is a critical ongoing process that is required as a precondition for the tar-
geting of novel products by means of high-throughput strategies. Public
and private interest has been growing over the last few decades, along with
their investments in marine biotechnology, which has further increased
the possibility of generating information and collecting huge amounts
of data to elaborate a better understanding of different cellular processes

and mechanism of biological actions. Furthermore, marine biotechnology
tends to utilize genomics, transcriptomics, proteomics, metabolomics,
metagenomics, and metatranscriptomics, etc. [25], in conjunction with
heterologous expression or genetic engineering to identify potential bioac-
tive species and increase the required constituents/substances production
[26].
A “test first” approach or an “isolate first” method is used in the screen-
ing process of natural goods, respectively. Natural bioactive components
have been discovered using both approaches, and a recent trend has been
to advocate the use of a fusion method, in which extracted or fractioned
extracts are evaluated for the presence of biologically active elements.
Bioassays are only utilized when the extracts demonstrate a high level of
biological activity [27]. In order to isolate or identify fractions of extracts
for chemical characterization, a number of techniques might be utilized.
One of these techniques is liquid chromatography–mass spectrometry
(LC-MS) and another is nuclear magnetic resonance (NMR). If novel con-
stituents are identified, they should be refined as well as evaluated utilizing
biological tests. Ideally, those tests should be reliable, repeatable, quick,
cost-effective, simple to run, and sensitive, and should also be reproduc-
ible [3].
Microorganisms play an increasingly significant role in modern life,
since they have evolved into essential components of a number of human
life functions, such as digestion and food assimilation, among others. They
also focus on human well-being by providing diversified foods, chemicals,
and medications. Many microbiological pathogens, including fungi, pro-
tozoa, viruses, and bacteria, are responsible for serious illnesses despite the
fact that effective management strategies are available. Bacteria and fungi
are responsible for the spoilage of food goods [6]. De Vera et al. carried
out experiments on more than 30 marine microalgae strains (haptophy-
tas, dinoflagellates, chlorophyta, and heterokontophytas) in order to obtain
extracts for evaluation of biological activity. As part of their research, they
chose a number of intriguing samples for additional investigation of marine
bioactive compounds. The unialgal isolates were kindly provided by the
Oceanographic Center of Vigo. The available strains were cultured in the
lab environment to determine their viability. Cell-free culture medium
extract and biomass extract (two types) were produced from each strain.
In order to get knowledge about antibacterial, antiproliferative, and anti-
cancer (apoptotic) characteristics, these two extracts were further analyzed
in order to get information on these qualities [28].
As per the current scenario on the non-selective and unsystematic

widespread use of antibiotics as antimicrobial agents, a new generation of
antibiotic-resistant and genetically modified microorganisms has emerged,
posing a serious threat to the treatment of infectious diseases. The nega-
tive consequences and side effects of frequently used antibiotics, as well as
the increasing prevalence of infectious diseases, have fueled the pursuit of
novel antimicrobial agents from diversified sources from the marine envi-
ronment [6].
1.6 Extraction Methods

Various methods or techniques can be utilized to separate potential ther-
apeutically or biologically active constituents from different varieties of
algal biomass. Various extracting agents were utilized to extract soluble
constituents derived from the microalgae matrix. The simplest approach
is to separate algal powder using water or organic solvents for large-scale
samples, with the latter being the preferred method. The extraction rates
vary from 8 to 30% of the dry algal yield under these conditions [29].
New types of extraction methods, like enzymolysis and extraction aided
by a microwave, have, however, recently emerged. The first has impressive
impacts, with high catalytic effectiveness characteristics, high specificities,
mild reactive and maximum efficiency [30]. Moreover, there were several
advantages to using the latter technique, including shorter processing
times, the use of less solvents, greater extraction rates, and the production
of better low-cost products [31, 32]. Complementary to the investigation
of soluble chemicals, cell-binding compounds (CBCs) that are attached to
the cell wall and cannot be easily isolated by applying the conventional
methods of isolation with aqueous solvents, are also being investigated.
This could also limit the study of marine-derived active components
and their potential industrial applications. Of interest is the enzyme diges-
tion of algae, which produces high biological yields compared to water
and organic extracts [33], and which exhibits improved biological activity.
Michalak and Chojnacka reviewed an examination on the use of enzyme
assistants using seaweed as an alternate approach for increasing the recov-
ery of industrially valuable chemicals from the sea [30].
Recent extraction methods extract biologically active constituents with-
out causing any loss of that activity. These are supercritical fluid extraction
(SFE), ultrasound-assisted extraction (UAE), and microwave-assisted
extraction (MAE). Among others, enzyme-assisted extraction (EAE) and
pressurized liquid extraction (PLE) also have the advantage of extracting
therapeutically active constituents. Moreover, this type of extraction

method is distinguished by a larger yield of extraction, a shorter process-
ing time, and, as a result, is more environmentally friendly as compared to
previous extraction methods. The extraction of soxhlets, as well as liquid–
liquid extraction along with solid–liquid extraction, are all examples of tra-
ditional extraction methods (SLE) [34]. Their primary disadvantage is the
use of a huge quantity of solvents (many of which are hazardous) and the
large amount of time needed for isolation [35].
Starting a decade ago, there seemed to be a substantial rise in the use
of alternative techniques to replace traditional methods largely due to
the numerous advantages of new extraction techniques. As per number
of authors, new green technologies (e.g., higher yields) are superior to
extraction by organic solvents, which incorporates the release of solvents.
These solvents could be potentially hazardous for the environment and can
also cause hydrothermal stress to extracts in terms of functional properties.
The degradation of thermally labile compounds may also result from the
high-temperature processing [36]. For instance, in the matter of the SFE
utilization with carbon dioxide, the yield of the lipid removal was higher
than in the case of Soxhlet solvent.
Because of the numerous advantages of new extraction techniques,
it has been noticed that they have increasingly been used to replace old
approaches in recent years. The superiority of new green technologies
(e.g., better yield) over extraction techniques by organic solvent has been
demonstrated by numerous authors. As a result of hydrothermal stress,
organic solvent extraction entails the release of potentially toxic solvents
into the surrounding environment. The functional characteristics of the
extracts were severely harmed as a result of the release of potentially haz-
ardous solvents. High-temperature processing can cause the deterioration
of components that are thermally labile as well as the degradation of other
constituents [36]. For example, when utilizing SFE with CO2, the amount of
lipid extracted from Sargassum hemiphyllum was greater than when using
the Soxhlet solvent extraction technique with chloroform/methanol [37].
Tierney et al. discovered in their research that PLE was more efficient than
standard SLE in the extraction of polyphenols using a water:acetone (20:80)
mixture [38]. Denery et al. also had a parallel observation that compared to
conventional solvent extraction techniques, PLE displayed more or equiv-
alent carotenoids extraction abilities from Haematococcus pluvialis as well
as Dunaliella salina [39]. Pasquet et al. examined extraction of pigment
from two marine microalgae using two different approaches (one is cold
and hot soaking and another is ultrasound-assisted extraction). Due to its
high rate, uniform heating, reproducibility, and higher separation rates,
MAE has been selected as the most effective pigment extraction technique
[40]. Authors investigated the emerging green technologies (such as MAE,
SFE and PLE) being more capable of replacing traditional organic solvent
extractions. Extraction with SFE is one of the most widely utilized meth-
ods of extraction on an analytic and preparatory scale nowadays [41].
Aim of this chapter is to show the unique qualities of biologically active
constituents and their wide applications obtained from algal biomass. The
utilization of extracts from various algae is widely described in different
areas of food, nutraceuticals and fuel manufacturing. It also explains the
application in agriculture (plants and animal products) and cosmetics of
algal extracts.
New extraction techniques are widely used in several industries for
obtaining algal extracts such as SFE, UAE, MAE, PLE, EAE, etc. These
techniques protect against degradation of the bioactive constituents iso-
lated from algae. Algae’s unique properties allow for a wide range of appli-
cations to be developed. They contain a high concentration of kilo grains
(such as eicosapentaenoic acid, docosahexaenoic acid, β-linoleic acid) and
in components such as polyunsaturated fatty acids (PUFAs) protein, min-
erals, carbohydrates, fats, oil, (e.g., docosahexaenoic acid, eicosapentaenoic
acid along with γ-linoleic acid), in addition to the amount of bioactive con-
stituents. These bioactive constituents are polyphenols, carotenoids, ter-
penoids, and tocopherols, which have antiviral, antibacterial, antifungal,
antioxidative, anti-inflammatory, and antitumor activities. For plants, ani-
mals and human beings, algal extracts generated in solvent-free conditions
or algal extracts obtained from minimal use of solvents are safe. These all
are used in modern agriculture for three different categories:
• Animals (feed additives),

• Plants (bioregulators, biostimulants, fertilizers), and
• Humans (food, cosmetics, pharmaceuticals) [31, 42].
1.7 Biosynthesis and Biological Activities

Due to the influence of time-course and cohabitation on biological sub-
stances, biochemical pathways have been developed to the point where
many microalgal lines now assemble a large number of distinct compounds.
Despite the fact that secondary plant metabolites are more comprehensive
than algae-derived metabolites, the diversity of secondary algal-derived
metabolites is orders of magnitude more than that of soil plants [5, 3].
Bioactive substances are additional nutritional components found in small
Table 1.1 Algae and cyanobacterial constituents with potential biological action.
Name of
microalgae Bioactive compounds Biological action Reference
Arthrospira PUFAs (n-3) fatty acids, Antiviral action [46–49]
platensis oleic acid, linolenic
(also known acid, (vitamin E),
as Spirulina phytol, palmitoleic
platensis) acid, sulfated
polysaccharide
Botryococcus Carotenoids, linear Antioxidant action [50, 51]
braunii alkadienes
Caulerpa racemosa Polyphenols Antioxidant action [52]
Chlorella Zeaxanthin, violaxanthin Anti-inflammatory [53, 54]
ellipsoidea action, anticancer
action
Chlorella Eicosapentaenoic acid Antioxidant action, [48]
minutissima (EPA) cholinesterases
inhibitory action
Chlorella Zeaxanthin, Anti-inflammatory [55–57]
protothecoides canthaxanthin, lutein action, antifungal
action
Chlorella Sulfated polysaccharide, Antiproliferative [49]
pyrenoidosa lutein action
Chlorella sp. Carotenoids poly- Immunostimulant [49, 53,
unsaturated fatty action, antitumor 58, 59]
acids, sulfated action, antioxidant
polysaccharides, action
sterols
Chlorella vulgaris Canthaxanthin, peptide, Antioxidant action [48, 53]
astaxanthin, oleic acid and antitumor
action
Chlorella Lutein, astaxanthin Anti-inflammatory [60, 61]
zofingiensis action
(Continued)
(Continued)
Name of
Cystoseira Polyphenols, neo- Antimicrobial action [62]
abies-marina, antioxidants, and and antioxidant
Halopitys amino acids action
incurvus
Dunaliella salina β-carotene (both trans Antioxidant action [48–50,
and cis geometric (restores the 63]
isomers), oleic activity of hepatic
acid, palmitic acid, enzymes)
linolenic acid
Dunaliella 7-Dehydroporiferasterol, Action on the [64]
tertiolecta ergosterol, nervous system
Oxocholesterol acetate
Eucheuma spinosa Different types of Antioxidant action [65]
galactose units
Gelidium pusillum R-phycocyanin and Hypocholesterolemic [66]
R-phycoerythrin action, antioxidant
action,
antineoplastic
action, anti-
inflammatory
action, and
hepatoprotective
action
Haematococcus β-Carotene, oleic Antioxidant action [46, 67,
pluvialis acid, astaxanthin, 68]
lutein, zeaxanthin,
canthaxanthin
Himanthalia Polyphenols, Antiviral action [69, 70]
elongata polysaccharides
Hormosira banksii
(Continued)
(Continued)
Name of
Isochrysis galbana Cholest-5-en-24-1,3- Antitubercular action [71]
(acetyloxy)-, and
3β-ol Ergost-5-en-
3β-ol, etc.
Laurencia obtuse Phenolic constituents Antioxidant action [72]
Lyngbya majuscula Lipopeptides Antitumor action [73, 74]
Nostoc Protein Antiviral action [75]
ellipsosporum
Nostoc Borophycin and Antibacterial action [48, 76]
spongiaeforme, cryptophycin
Nostoc linckia
Nostoc sp. Cyclopeptide Antineoplastic action [77]
GSV 224
Saccharina Fucoxanthin, Antineoplastic action [78–80]
japonica polyphenols, and antioxidant
carotenoids, and action
phlorotannins
Sargassum Polyphenols, neo- Antimicrobial action [62]
muticum, antioxidants, amino and antioxidant
Sargassum acids action
vulgare
Sargassum Polysaccharides Antioxidant action [81]
thunbergii and antidiabetic
action
Scenedesmus Polyphenols, flavonoids Antioxidant action, [82]
bajacalifornicus and alkaloids antidiabetic action,
anti-inflammatory
action
Scytonema varium Polypeptide constituents Antiviral action [83]
(Continued)
(Continued)
Name of
Skeletonema Nucleoside inosine Antiepileptic action [84]
marinoi
Spirulina Phycobiliproteins, Antibacterial action [48, 85]
fusiformis diacylglycerols
Spirulina sp. Polysaccharides Antiviral action [53]
phycocyanin,
C-phycocyanin,
phenolic acids,
tocopherols
Ulva prolifera Polysaccharides Antioxidant activity, [86]
antihyperlipidemic
action
Undaria Neo-antioxidants, Antihyperlipidemic [62]
pinnatifida polyphenols, and and antioxidative
amino acids properties
amounts in foods. A variety of bioactive substances appear to provide

health benefits. Microalgae and Cyanobacteria have been discovered to
have a large number of physiologically active chemicals having antiviral,
antibacterial, antifungal, and anticancer properties [43]. Phytoplankton
(microalgae) are a diverse community of microscopic plants which also
involve a diverse and wide range of physiological and biochemical charac-
teristics, including up to 8–14% carotene, up to 50–70% protein (roughly
equivalent to up to 50% protein in meat and 15–17% protein in wheat),
over 40% glycerol, 30% lipids, and a notably higher concentration of water-
soluble vitamins (B1, B2, B3, B6, B12) and fat-soluble vitamins (E, K, D)
and others. A record of various bioactive constituents from algae along
with cyanobacteria is presented in Table 1.1 [5, 22, 44, 45].
1.7.1 Antibacterial Action

In order to protect themselves from other invading organisms, algons pro-
duce an immense variety of chemically active constituents which include
terpenoids, phlorotannins, amino acids, phenolic compounds, steroids,
alkenes, cyclic polysulfide and halogenated ketones [87]. Furthermore,

organic extracts made from Chaetoceros pseudocurvisetus and the diatoms
Skeletonema costatum were looked into and found to have antitubercular
activity towards Mycobacterium tuberculosis and Mycobacterium bovis by
Lauritano and his team, and according to various researchers, in stan-
dard human cell lines, they were found to be nontoxic [88]. Phlorotannins
(derived from Sargassum thunbergii) have been shown to inhibit the growth
of Vibrio parahaemolyticus, as a result of which membranes are destroyed
and insignificant cytoplasmic leakage takes place [60]. Various bacteria,
including Candida albicans, Staphylococcus aureus, Aspergillus niger, and
Escherichia coli, have been shown to be susceptible to Haematococcus plu-
vialis. The susceptibility noticed is because of the presence of propanoic
and butanoic acid molecules in the bacteria [89].
Spirulina fusiformis consisting of phycobiliproteins showed strong anti-
bacterial action towards Streptococcus pyogenes and Spirulina fusiformis
phycobiliproteins [84]. Synechocystis sp. extracts containing fatty acids
reduced the development of the bacteria Bacillus cereus and E. coli, C. coli,
as well as C. albicans. The C-phycocyanin generated by Streptomyces plat-
ensis seems to suppress the spread of Pseudomonas aeruginosa, Salmonella
enteritidis, S. aureus, E. coli, and Klebsiella pneumoniae in vitro [90].
Algal polysaccharides resembling fucoidan and laminar are demonstrated
to possess antibacterial action against Staphylococcus aureus and E. coli
strains. According to some previous reports, it has been proven to impede
the formation of Helicobacter pylori biofilms in the mucosa of stomach [91]
as well as the proliferation of H. pylori [86]. Kubota et al. discovered that the
bioactive constituent amphidinolide Q, which comes from the Amphidinium
sp. (symbiotic dinoflagellate), was effective towards the bacteria Bacillus sub-
tilis, Staphylococcus aureus, and Escherichia coli, as well as others [92].
Algal polysaccharides (fucoidan- and laminarin-like) showed efficient
antimicrobial activity towards E. coli and Staphylococcus aureus strains.
They have been shown to impede the production of Helicobacter pylori
biofilms in the mucosa of stomach [93] and the growth of H. pylori [86].
The bioactive ingredient amphidinolide Q from the Amphidinium sp. was
effective against the bacteria B. subtilis, S. aureus, and E. coli [92].
Pahayokolide A appeared to inhibit the formation of Bacillus megate-
rium and Bacillus subtilis, as well as exhibiting cytotoxic properties [94]
derived from Lyngbya sp. [95]. Antibacterial activity against MRSA and
vancomycin-resistant Enterococcus faecium (VRE) was demonstrated by
the chemicals bromophycolide P and bromophycolide Q. These were sep-
arated from the Fijian red alga Callophycus serratus [96]. Neuraminidases
A and B, two pyrone macrolides derived from the red alga Neurymenia
fraxinifolia [97], were found to have antimicrobial efficacy towards MRSA

and VRE. A compound found in Phaeodactylum tricornutum, EPA, palmi-
toleic and hexadecatrienoic acids, among others, could reduce the growth
of bacteria such as B. cereus, S. aureus, S. epidermidis, MRSA, and others
[98]. Bacillus subtilis, Micrococcus flavus, and Staphylococcus aureus growth
have been shown to be effected and inhibited by fatty acids derived from
Oscillatoria redekei containing dimorphecolic, coriolic, and linoleic acids
[99]. Antibacterial activity towards E. coli, S. aureus and B. subtilis was
also observed in lipid fractions from Chaetoceros muelleri. They were also
known to contain unsaturated fatty acids [triglycerides and docosapentae-
noic acid (DPA)]. Mendiola et al. discovered DPA was present in unsatu-
rated fatty acid from Chaetoceros muelleri. Many antimicrobial compounds
discovered from the Nostoc sp., including noscomin, which was acquired
from the terrestrial Nostoc commune. It was shown to possess antibacterial
action towards bacteria such as E. coli, B. cereus, and S. Epidermidis [100].
It has been suggested that Muscoride A, an alkaloid derived from the plant
Nostoc muscorum, may have antibacterial action towards E. coli and B. sub-
tilis [101].
1.7.2 Antifungal Action

Antifungal activity of ethanolic fractions of Laurencia paniculata was
investigated by Mickymaray and Alturaiki [102], which contained the ses-
quiterpene constituent aristolene in patients with bronchial asthma. The
results revealed that the fractions had antifungal activity, particularly in
patients with bronchial asthma. It was discovered that the compounds iso-
lated from Microcystis aeruginosa demonstrated antifungal action, partic-
ularly towards the fungus Aspergillus. Hexadecanoic acid, methyl ester, and
BHT were all found to be effective [102]. Shishido et al. and Marrez and
Sultan identified scytophycin as a strong antifungal chemical from species
of Nostoc, Scytonema, and Anabaena sp. [103, 104]. Researchers discovered
other various types of antifungal chemicals called hassallidins from Nostoc
sp. and Anabaena sp. The Amphidinium sp. as a symbiotic dinoflagellate
[92], displayed antifungal efficacy towards Candida albicans due to derived
chemical amphidinolide Q. Phycobiliproteins produced by Porphyridium
aerugineum have the potential to provide resistance against Clostridium
difficile. C. albicans is an acronym for Candida albicans [84]. Chlorococcum
humicola growth was discovered to be inhibited by pigments and organic
solvent extracts from C. humicola, such as chlorophyll a, carotene, and
chlorophyll b, which were proven to be effective against the growth of
the bacteria. There are many different types [4] such as Aspergillus flavus,
A. albicans, Aspergillus niger and others. When tested against Aspergillus

candidus, nostofungicidine, which is produced from N. commune, showed
significant antifungal effectiveness, according to the researchers [87]. The
fatty acids having short chain produced from H. pluvialis were found to
be effective against C. albicans in a laboratory setting [69]. Lipopeptides
laxaphycin B along with laxaphycin C are obtained from species Anabaena
laxa. These constituents displayed antifungal action towards C. albicans,
Saccharomyces cerevisiae, Aspergillus oryzae, Penicillium notatum, and
Trichophyton mentagrophytes [105]. Dahms et al. observed antifungal
properties of fisherellin from Fischerella muscicola [106]. Ciguatoxin and
okadaic acid are effective chemicals against fungi, synthesized by Giardia
toxics and Prorocentrum lima, respectively [107]. In 2006, Washida et al.
reported antimycotic activities. This action was shown by karatungiols.
Its constituents were derived by the dinoflagellate Amphidinium [108].
Hassalldin A as well as Hassallidin B were obtained from Hassallia sp. dis-
played fungicidal properties [109] towards Acremonium strictum, Fusarium
sp., Aspergillus sp., Ustilago maydis, Penicillium sp. and Cryptococcus neo-
formans. Hapalosiphon welwitschii as well as Westiella genus were also dis-
covered to possess fungicidal agents such as N-methylwelwitindolinone C
isocyanate and welwitindolinone A isonitrile [110].
1.7.3 Anti-Inflammatory Action

Whenever something affects, irritates, or damages our body, we experi-
ence inflammation as a quick reaction. As part of this response, the body
recognizes the agents accountable for the attack and gets a chance to neu-
tralize them as soon as feasible. Pain, redness, swelling, and warmth are
all symptoms of inflammation that usually occur at the infection site. The
anti-inflammatory chemicals absorption aids in the prevention of ill-
ness and the speeding up of the healing process. It regulates the immune
response of body to the infection. Anti-inflammatory medicines derived
from microalgae are widely used nowadays. When combined in food or
applied topically in cosmetics and other pharmaceutical products, they are
protective to the body’s tissues. Researchers found that sulfurized poly-
saccharides as well as pigments [111] and PUFAs are the most import-
ant anti-inflammatory substances found in microalgae around the world
[112]. The immunological response to many cyanobacterial polysaccha-
rides can be improved by reacting through a variety of events, including
reactive oxygen species, macroelectric phenomena, secreting chemo-
cytokines and cytokines. As per J. K. Park et al., these are signalling inflam-
matory and immune responses. The introduction of reactive oxygen into
various cyanobacterial polysaccharides is responsible for the activation of

macrophage functions in the body. As a result of the chemical cytokines
it secretes, cytokines can boost immune responses through a variety of
mechanisms, including signaling immunological as well as inflammatory
responses [113]. As a result, more types of cytokines were stimulated for
further secretion [114]. Phycocyanine is one of the most essential cyano-
bacterial pigments and denotes a phycobiliprotein. It works as a photosyn-
thetic antenna by the collection of light and energy. Phycocyanins recently
became a highlight in medicine because they have various pharmaceu-
ticals, like anti-inflammatory, antioxidant, and antineoplastic actions.
The cytokines produced in greater quantities are responsible for anti-in-
flammatory action [115]. They inhibit the COX-2 enzyme which further
inhibit the synthesis of prostaglandin E2 synthesis (PGE2). Based on its
pharmacological action and distinctive properties, phycocyanin may be
developed as a possible therapeutic agent against inflammation and neu-
rodegenerative diseases. Different types of neurodegenerative diseases are
Alzheimer’s disease (memory loss), Parkinson’s disease (personality disor-
der), Huntington’s disease, etc. [116].
The pigment scytonemin was discovered in cyanobacteria as a second-
ary metabolite containing an aromatic alkaloid [117, 118]. According to
the literature, its anti-inflammatory function on another normal cell has
been shown to have no harmful effects. Scytonemin has also been pro-
posed for use in the creation of an anticancer treatment that inhibits the
advancement of the cell cycle [5].
1.7.4 Antiprotozoal Action

The antiprotozoal activity of several cyanobacterial compounds against
the pathogenic parasite has been demonstrated in laboratory studies
(e.g., malaria caused by Plasmodium falciparum, leishmaniosis caused by
Leishmania donovani and sleeping sickness caused by Trypanosoma bru-
cei). However, some cyanobacterial metabolites, particularly those that
are effective against drug-resistant strains, also have antiprotozoal activ-
ity. The companeramides A and B are metabolites separated from the
plant Leptolyngbya sp. which are cyclic depsipeptides. Now Hyalidium
has been explored extensively by researchers [119]. These compounds, on
the other hand, have antimalarial efficacy against three separate strains
of Plasmodium falciparum which are chloroquine-resistant. Their thera-
peutic activity against a parasite is one hundred times lower than that of
chloroquine, which limits their potential use as pharmaceutical agents in
treating parasitic infections. Even so, some metabolites have shown a high
efficacy against the parasite, so they might replace antibiotic medications

like dolastatins and hoshinolactam for protozoal infections. Dolastatins
are indeed natural marine peptides and Dolabella auricularia (sea hare)
was identified as the first members of this family [22].
Antiprotozoal activity [120] against the Trichomonas vaginal, Entamoeba
histolytica, Leishmania mexicana, Trypanosoma cruzi, Giardia intesti-
nalis, etc., has been shown in Lobophora variegata extracts. Alkaloids of
Cladophora crispate along with ethyl acetate constituents were found to
possess antiprotozoal action towards protoscolices of Echinococcus gran-
ulosus hydatid cysts. The ethyl acetate constituents and alkaloids were
isolated from the plant Cladophora crispate [121]. Inhibition of growth
of Leishmania braziliensis was observed in algal extracts from the follow-
ing species: Canistrocarpus cervicornis, Caulerpa cupressoides, Ochtodes
secundiramea, Anadyomene saldanhae, Dictyota sp. and Padina sp. [122].
A polyanionic sulfated polysaccharide known as fucoidan [123], prevalent
in numerous brown algae, was discovered. It has been shown to have an
inhibitory effect on the intracellular amastigote part of Leishmania dono-
vani. Dolabelladienetriol, derived from the Diktyota pfaffii plant, was tested
for its leishmanicidal action against intracellular amastigotes. It was also
found effective for antihuman immunodeficiency virus (HIV)-1 action.
As HIV-1 has been shown to increase the amount of Leishmania parasites
present in macrophages, dolabelladienetriol seems promising for chemo-
therapy of leishmaniasis. Elatol isolated from Laurencia dendroidea (the
Brazilian red algae) [124], demonstrated antiprotozoal activity towards the
amastigotes and trypomastigotes of T. cruzi species.
The Sargassum hemiphyllum has constituent sargaquinoic (meroter
penoid) [125], which was a powerful agent against in-vitro Plasmodium
falciparum [126]. Fennel et al. discovered that, irrespective of its strong
actions, dolastatins are not recognized as promising antiprotozoal drugs.
Hoshinolactam is an aromatic metabolite of the lactam family pro-
duced by cyanobacteria. Separated from Oscillatoria sp., it demonstrated
antiprotozoal action with IC50 equivalent (3.9 nM) to the commercial
medicinal product pentamidine (4.7 nM) against Trypanosoma brucei
[127]. Therefore, it has the potential to be utilized as effective alternate
medication for trypanosomiasis caused by Trypanosoma brucei. Marine
algae have various bioactive compounds with antimalarial/antiprotozoal
activities which still need to be explored.
1.7.5 Antioxidant Action

The demand for algal foods is rising rapidly on the global platform,
with excellent health benefits being used on the market as “functions or
nutraceuticals.” It is possible to prevent oxidative damage in cells caused by

bioactive chemicals through a process of active oxygen and scavenging free
radicals, which can help prevent cancer [128]. Serious health conditions
like atherosclerosis, cardiac ailments, strokes, tumors, neurodegenerative
disorders, muscular degeneration, infant retinopathy, renal disease and
age-related diseases, are caused by oxidative stress [129]. Different algal
constituents have antioxidant properties, in addition to anti-inflamma-
tory, antibacterial and antiviral effects in reduction and/or disease preven-
tion. These components are linolenic acid [130], cyanocyanine, oleic acid
[46], B-12, vitamin E, palmitoleic acid [131], β-carotene, phycocyanin,
zeaxanthin, etc. [55].
Inverted association with the consumption of fruit and vegetables was
established in epidemiological studies. The antioxidant activity of these
foods is attributed to this phenomenon [7]. Cyanobacterium phytochem-
icals along with pigments possess a active oxygen-free radical, or nitrogen
scavenger, and therefore act as antioxidant. Often high oxygen levels and
high irradiation are subjected to algae and cyanobacteria. These organ-
isms tend to form an oxidative stress defense mechanism. The antioxidants
found in microalgae (dimethyl sulfoniopropionate and mycosporic amino
acids) have been identified and are extremely strong molecules that block
ultraviolet light [132]. Skjånes et al. discovered that algae possess a variety
of constituents that have antioxidant properties, including pigments, lip-
ids, and polysaccharides [133].
1.7.6 Antineoplastic (Anticancer) Action

The photosynthetic microbes, including cyanobacteria and algae, devel-
oped to survive and flourish in a hostile atmosphere on the biochemi-
cal basis of bioactive compounds and secondary metabolites. Separated
secondary metabolites have a high therapeutic value, which is further
enhanced for antineoplastic properties by active pharmacological ingredi-
ents [2]. Cyanobacteria strains, such as Oscillatoria, Nostoc, and Spirulina,
generate a mixture of acetyl Co-A synthesis and anabolic pathways to
produce cytotoxic lipopeptides [23]. Recently, researchers discovered
that somocystinamide, a marine lipopeptide derived from the seaweed
L. majuscula, can activate the apoptosis pathway and restrict the growth
of numerous cancer cell lines, including leukaemia. Others are carcinoma,
melanoma, neuroblastoma and myeloma [73]. Didemnin [74, 134], lyngb-
yabellins [135], and hectochlorin are examples of lipopeptides that have
been discovered [136].
Cyclopeptide cryptophycin produced by Nostoc also has demonstrated

a great potential for anticancer to multidrug-resistant cells because of
their effects on the cytoskeletal protein tubulin. Besides which, the effects
against solid tumors have been highly effective. The cancer suppression
mechanism has been connected to binding of tubulin [137, 138], which
results in the depolymerization of microtubules [139] and the instability
of microtubules, which results in cell cycle arrest and apoptosis, among
other things [1]. Similarly, apratoxin A, a natural compound derived from
marine cyanobacteria, inhibits the transcription factor STAT3 [140], which
prevents G1 cells from becoming cancerous and induces apoptosis in dif-
ferent cell types [141, 142]. Based on their adaptation to exposed anthro-
pogenic environment, cyanobiological flora in freshwater ponds generates
an unpleasant smell. These blooms (blooms are accumulation of algal cells
to any point where they discolor the water) of blue-green algae cultivate in
vast numbers and are harmful to all creatures because of their cyanotoxin
content. However, the promising properties of these toxins as anticancer
drugs have been demonstrated. The clinical effectiveness of different car-
cinomas has been demonstrated by microcystins, cryptophicins, anatoxin
A and numerous peptide toxins [143, 144]. Successful clinical trials of cya-
nobacterial depsipeptides like dolastatin 15, including tasidotin, soblidotin
and cemadotin, were carried out [1]. A significant element in chemother-
apy is the mechanism by which cyanobacterial metabolites act on tumor
cells. Cells are programmed for apoptotic cell death to die from stimulus
by changed homeostasis caused by infections, oncogenic transformations,
oxidants, abnormal proliferation, and so on. There is therefore a high
pharmacological value for anticancer treatment for metabolite-inducing
apoptosis. A class of anticancer compounds known as cyanobacterial
metabolites interconnect with molecular cell parts, such as DNA, pro-
tein kinases of the receiver and microtubules. Cell cycle controls protein
synthesis. These interactions result in cell blockage [145], mitochondrial
dysfunction, oxidative damage [146], and non-cascade activation [147].
Different pharmacoactive cyanobacterial constituents for powerful anti-
cancer and apoptotic signalling have been tested. Calothrixin A revealed
cell cycle G2 phase or M phase arrest in tumor cells of humans. Calothrixin
A is a class of indolophenanthridine obtained from Calothrix [148]. So,
phycobiliprotein (C-phycocyanin) was mentioned as scavenging peroxyl
and phormidium radicals from both Lyngbya and Phormidium [149].
Besides the abovementioned apoptotic markers, the sodium concen-
tration in the cells is enhanced apart from a few metabolites, such as the
antillatoxins as lipopeptides separated from the majuscula [150], and the
hermitamides [151]. In marine environment, microalgae growing covers
nearly forty percent of worldwide economic output. Microalgal bloom nat-

ural products were already extensively investigated for bioactive antineo-
plastic compounds, polysaccharides, pigments, and secondary metabolites.
Whereas C-phycocyanin and phycobiliprotein, from both Phormidium
and Lyngbya, were discovered to neutralize, i.e., scavenging radicals of
hydroxyl and peroxyl [149]. When cultures are cultivated under specified
conditions, such as in specialized medium, at specific temperatures, and
under specific light, microalgal extracts have been proven to be effective in
anticancer (antineoplastic) research [88].
In general, carotenoids, such as lutein, alpha-carotene, beta-carotene,
xanthene, lycopene, and other terpenes found in algae and cyanobacteria,
are abundant because they are photosynthetic byproducts. As a scavenger
for singlet electron species, carotenoids and various terpenoids play a cru-
cial role. All these scavengers are therefore used to avoid the proliferation
of cancer cells as an antioxidant. In various cancers, there are few reports
of carotenoid cancer activity. However, some cases had inversely affected
the development of carotenoids, which subsequently was detected due to
smoking effects in individuals affected by lung cancer [80]. However, the
neoplasm proliferation risk was reduced by dietary carotenoids studied by
numerous authors [152].
Algae water extracts mainly constitute chemical molecules like alkalis,
polysaccharides, polyphenols, polyunsaturated fatty acids (PUFAs), fatty
lipids, glycoproteins, terpenoids and vitamins. Many of these constituents
were examined and discovered as efficient in producing anticancer activ-
ity. The anticancer properties of a few secondary metabolites, including
hormothamnione A from Chrysophaeum taylorii, hormothamnin A in
Hormothamnion enteromorphoides, and malyngamide D in L. majuscule
[153], have been discovered after extracts of these plants were made and
tested on numerous cell lines. In addition to studies involving active mole-
cules, a number of experiments were carried out to establish antineoplastic
efficacy utilizing crude extracts, for example, extract of carotenoid [154],
crude organic solvent extracts [155], polyunsaturated aldehydes [156], and
chrysolaminarin (polysaccharide) [157].
It could be expected that in the current scenario of several tumor
ailments, microalgae-based nanoformulated delivery systems must be
marketable presently. In the literature, however, the above aspects have
not been explored up to now for marketing nanoformulation or sustain-
able, efficient formulations and proper use of microalgae medications in
nanomedicine-based therapy. It might be good to test for the nanofor-
mulation’s marketing in cancer therapy with diatoms and other microal-
gal specimens without the danger of experiencing any adverse effects in
order to determine their effectiveness. Studies in this area will provide

future opportunities to exploit or capitalize on the possibilities of marine
natural microalgal-derived compounds with nanoformulated therapeu-
tic activities [158].
1.7.7 Antiviral Action

Despite the fact that successfully reported vaccine inventions have pro-
vided acquired immunity, current efforts to develop medications such as
antivirals have expanded dramatically as new or re-emerging infectious
diseases have evolved or reappeared. Because viral pathogenic organisms
can rapidly manipulate genetic make-up at a time when a treatment strat-
egy is witnessed that results in drug resistance, it is possible that this is the
case [159]. Algae are one source, which are well-known for their many
medicinal properties.
Recently, researchers discovered that the Phormidium tenue and
Lyngbya lagerheimeii cyanobacteria have antiviral activity towards HIV,
also known as the human immunodeficiency virus. In the following
years, researchers discovered and identified a novel family of anti-HIV
protein known as Cyanovirin-N [75], which restricts the virus from fus-
ing with the cell and, as a result, renders the viral particles inactive [160].
Afterwards, calcium spirulan, a new SP, was discovered in Spirulina plat-
ensis. It was reported to supress the reproduction of enveloped viruses of
a large range, including the human cytomegalovirus [47], Herpes simplex
virus type 1 (HSV-1), influenza A virus, mumps virus [161], HIV-1, and
measles virus, among others [162]. The antiviral activity of spirulina-like
compounds derived from Arthrospira platensis polysaccharide fractions
was enhanced against human cytomegalovirus (HSV-1), which was pre-
viously reported [163].
In vitro antiviral activity against human cytomegalovirus, also known
as HSV-1, was enhanced by a class of spirulina-like compounds derived
from Arthrospira platensis polysaccharide fractions [163]. Microcystis ich-
thyoblabe produce depsipeptides A and B, which have been demonstrated
to impede the replication of the influenza A virus [164]. According to an
article written by Vijayakumar and Menakha, Nostoflan, a virucidal med-
icine for HSV-1, was produced by Nostoc flagelliforme [142]. Scytovirin,
when used in nanomolar quantities, binds to the HIV glycoprotein and
causes the virus’ protein envelope to degrade [83].
For several decades, many polysaccharides identified in marine algae
species were investigated and revealed to possess intriguing antiviral
properties [165]. As an example, carrageenan, a compound derived from

the red algae Gigartina skottsbergii, has been discovered to be thera-
peutically active against viruses (both non-enveloped and enveloped).
Polysaccharide samples, such as calcium spirulan, nostaflan and naviculan
from diatom Navicula directa, and galactan from red algae, have also been
discovered to possess unexpected antiviral properties against HSV, DENV,
HPV, HIV, and other viruses [165].
1.7.8 Anticoagulant Action

Marine algae are very important bioactive constituent possessing an anti-
coagulant property among all other marine sources. Phlorotannins pro-
duced from marine algae have shown tremendous promise in biomedical
research as anticoagulant medicines [166]. Prothrombin time, activated
partial thromboplastin time, as well as thrombin time are all measured to
assess whether or not a medication has anticoagulant action. According to
the findings of a study, substances containing anticoagulant proteins and
antiplatelet as well as fibrinolytic enzymes, have the potential to regulate
endothelial cell activities and trigger the fibrinolysis system [167].
Natural and healthy anticoagulant compounds that generate phe-
nolic constituents or phlorotannins are derived from, for example,
Ecklonia stolonifera, Hizikia fusiformis, Ecklonia cava, Ecklonia kurome,
Ishige okamurae, Eisenia bicyclis and S. thunbergii [166]. Brown algae’s
fucoidan along with laminarans, red algae’s carrageenan, and green
algae’s ulvan have all received a lot of interest in the sectors of food,
cosmetics [168], and pharmaceuticals [169]. Due to their good health
benefits, these oceanic algae are being explored as possible medicinal
medication components.
1.7.9 Immunosuppressive Action

Immunosuppressive medicines, notably T and B cells, have the tendency
to suppress the immune system in a variety of ways. They are essential in
order to increase the probability of surviving allogeneic organ transplan-
tation by lowering immunological responses of the host. An immunosup-
pressive effect of SQDG (sulfolipids) derived from blue-green algae was
observed in a study to be significant in a human-mixed lymphocyte reac-
tion while having no influence on overall immune competence [170]. The
bioactive protein found in Spirulina (blue-green algae) boosts the intesti-
nal immune system by a variety of ways [171]. Spirulina has been studied
for its potential to protect the kidney from heavy metals and pharmaceuti-
cals by lowering glucose and lipid levels in the blood [172]. Chlorella’s -1,3
glucan lowers blood cholesterol and free radicals [10]. Several immuno-
suppressive bioactive chemicals are found in blue-green algae.
Our goal in this chapter is to reveal the biological production of bioac-
tive compounds by various green algal species. This review confirms that
a variety of green algae possess biological active compounds. The phyto-
chemicals in these algae show various beneficial effects, which was sup-
ported by variety of the literature.
1.8 Conclusion
Nature and its chemical equivalents are the principal sources of medicinal
molecules used on a daily basis. Bioactive chemicals derived from algae
have been widely studied for antibacterial, antioxidant, anti-inflammatory,
anticoagulant, antiprotozoal, antitumor, and antiviral applications over the
past several decades. In order to survive under severe environmental con-
ditions, algae and cyanobacteria have developed natural defense mecha-
nisms via the creation of bioactive compounds. Stress factors and oxidants
were neutralized by bioactive molecules such as alkaloids and terpenoids.
Extracted algal ingredients were examined for bioactivity against bacteria,
fungus, viruses, and protozoa. In strict clinical tests, the proliferation of
cancer was also inhibited.
In light of microalgae’s shown ability to create bioactive compounds,
these microorganisms have been thrust into the biotechnology limelight
for potential uses in a wide range of fields of research, particularly the life
sciences. Since the discovery of microalgal metabolites, which boost the
body’s defense mechanisms, researchers have been studying the use of
microalgal biomass in a variety of meals, pharmaceutical products, and
medicinal items. The found chemicals and their activity in the preven-
tion as well as cure of numerous ailments, as well as the ongoing search
for other, as of yet unreported metabolites, are clearly in need of further
investigation.
Marine biotechnology in pharmaceuticals and food applications is an
emerging sector that is globally encouraged by an increasing number of
policy and financial instruments. Techniques for the optimization of
culture conditions, harvesting and extraction methods, combined with
recombinant techniques, have become essential to the majority of indus-
trial models that may be put to achieving corporate use, especially in food
and nutraceutical applications. The emergence of this sector has been
facilitated by the growing consumer demand for healthy foods that also
have beneficial effects on health, combined with a less stringent legislation
than that which applies to pharmaceutical substances [12].
Furthermore, in extreme temperatures worldwide, there are several
algal and cyanobacterial bases and the pressure has yet to be identified.
With vigilance, the identification and cultivation of these species could dis-
cover some new chemical compounds which can produce high therapeutic
effectiveness. Such pharmaco-active moieties may, as observed for dolastatin
10, also be modified into analogues to improve clinical utilization. Besides,
at the same time, a combination of two or more medicinal compounds can
contribute in identifying and evaluating antagonistic, additive, or synergis-
tic effects by in-vitro testing and clinical trials on animals to decrease tox-
icity problems. The challenge is still there to optimize our ability to access,
identify as well as exploit them while remaining cost-effective. The task for
researchers is also to establish the circumstances in which the large pro-
portion of these microbes could be cultivated in order to provide a reliable
source of supply in the future.
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2
Bioactive Compounds Synthesized
by Algae: Current Development and
Prospects as Biomedical Application
in the Pharmaceutical Industry
Preeti Mishra1*, Namrata Gupta2, Monika Singh1 and Deeksha Tiwari2
Faculty of Pharmacy, Raja Balwant Singh Engineering Technical Campus,

1

2
Faculty of Engineering, Raja Balwant Singh Engineering Technical Campus,
Abstract
Algae and microalgae are a diverse group of organisms that contain a diverse
range of bioactive chemicals, including pigments, polyunsaturated fatty acids,
polysaccharides, polyphenols, and other bio-algae and microalgae, as well as
their bioactive chemicals, which have antioxidant, anti-inflammatory, anticancer,
and antiobesity characteristics, making them ideal for use in food preparation.
Because of the tremendous diversity of organisms and molecules, new effects and/
or compounds will inevitably be found in the future. A growing number of people
are becoming interested in algae extracts as a result of their particular composition
and potential for use in a wide variety of industrial applications. Algal biomass is
transformed into extracts by the use of several extraction techniques.
Microalgae bioactive compounds offer a variety of beneficial effects, includ-
ing anti-inflammatory, antibacterial, and antioxidant capabilities. These bacteria
also have the potential to promote health and reduce the risk of degenerative dis-
orders, according to researchers. As outlined, the purpose of this chapter is to
describe bioactive metabolites generated by microalgae and their potential uses in
the pharmaceutical sector.
41
Keywords: Microalgae, bioactive compounds, carotenoids, polyunsaturated fatty

acids, protein and polypeptides
2.1 Introduction
Algae are photosynthetic microorganisms that live and grow in water under
hydroponic conditions, allowing them to absorb carbon in heterotrophic
and mixotrophic environments [1]. The vast majority of algae are found in
fresh or salt water, where they can either float freely (planktonic) or stick
to the bottom of the water body. Algae may grow on rocks, soil, and plants
as long as there is enough moisture present to support growth. Lichens can
form when a small number of algae build tight interactions with fungus.
The hairs of the South American sloth and the polar bears are remarkable
algal habitats because they are so thick. Chlorophyll is a pigment found in
algae (other types of chlorophyll, such as b, c, and/or d, may also be pres-
ent), and algae employ photosynthesis to generate their food. Chlorophyll
is found in the chloroplasts of algae, and it is responsible for the green color
of many algae. However, some algae appear brown, yellow, or red because
they contain additional pigments that, in addition to chlorophylls, conceal
the green color [2]. Microalgae are unicellular microorganisms that may
be found in a variety of forms and sizes with a diameter or length ranging
from 3–10 μm [3]. These bacteria are responsible for around 40% of all
photosynthesis on the planet [4]. Changes in the external environment cre-
ate changes in the internal environment in the metabolism of microalgae,
and the reverse is true as well. When the culture conditions are altered,
the presence or absence of specific nutrients, for example, might cause the
production of specific compounds to increase or decrease. The bioactive
chemicals synthesized by microalgae include proteins, fatty acids, vitamins,
and pigments, all of which can be taken directly from primary metabolism
or created indirectly through secondary metabolism [5]. These compounds
possess antifungal, antiviral, antialgal, anti-enzymatic, and antibiotic capa-
bilities, among other characteristics. Numerous chemicals in this group
(cyanovirin, oleic acid, linolenic acid, palmitoleic acid, vitamin E, B12,
β-carotene, phycocyanin, lutein, and zeaxanthin) possess antibacterial and
anti-inflammatory characteristics, and as a result, can decrease and pre-
vent sickness [3]. Most microalgae collect bioactive compounds in their
biomass; but, in rare instances, these metabolites are expelled into the sur-
rounding media and are referred to as exometabolites. Bioactive metabo-
lites derived from microalgae are of great relevance in the creation of novel
Bioactive Compounds Synthesized by Algae 43
products for the medical, pharmaceutical, cosmetic, and food industries.

Further research into these bioactive compounds is required to validate
their beneficial effects on humans, their environmental degradability, and
their effects when used in animal experiments [3].
Marine algae are rich in bioactive nutraceuticals (carbohydrates, pro-
teins, minerals, fatty acids, antioxidants, and pigments), which are benefi-
cial to human health. Natural secondary metabolites are produced by algae
in response to environmental factors, including biotic (plants, microorgan-
isms) and abiotic factors such as temperature (pH, salinity, and light inten-
sity). Simple, cost-effective, and long-term recovery options include novel
solid-liquid and liquid-liquid extraction techniques (e.g., supercritical,
high pressure, microwave, ultrasonic, enzymatic) and novel solid-liquid
separation techniques [6]. Because marine microalgae and cyanobacteria
contain a diverse range of chemical substances, they have the potential to
be used in biological applications that have health benefits. Microalgae
can be used to produce a wide range of chemicals, including polyphenols,
polyunsaturated fatty acids (PUFA), and phytosterols. In contrast, unex-
plored natural sources of bioactive components are gaining a great deal of
research since they have the potential to lead to the identification of new
molecules or bioactivities [5].
2.2 Algal-Sourced Compounds of Medical Interest

Throughout the last few decades, marine algae have attracted consider-
able attention as a potential source of potential renewable energy. There are
more than 8000 unique types of marine algae species that have been iden-
tified throughout the world, according to recent research [6–8]. Primary
and secondary metabolites (e.g., polysaccharides, proteins, amino acids,
dietary fibre, essential fatty acids) found in seaweeds, including pigments,
phytosterols, polyphenols, terpenoids, carotenoids, tocopherols, min-
erals, and vitamins, have been shown to have antiviral, antihelminthic,
antifungal, and antibacterial properties in laboratory studies. Based on
their mechanistic differences, physiologically active compounds found in
marine algae can be divided into two categories [8, 9]: (i) non-absorbed
high-molecular materials and (ii) absorbed low-molecular materials,
both of which have direct effects on human homeostasis; and absorbed
low-molecular materials. These substances are now widely used in both
fresh and processed foods, and they have gained prominence in nutri-
tional science as a result of their potential pharmacological applications
as antioxidants, anti-inflammatories, anti-proliferative (including tumor

suppression), antithrombotic, anticoagulant, antihypertensive, antidia-
betic, and cardioprotective agents (among other things). The development
of novel drugs generated from macroalgal biocompounds that are clini-
cally viable and commercially available in cancer, infection, diabetes, and
neuroprotective formulations has emerged as a rapidly expanding phar-
macological specialty. Furthermore, various research studies aiming at the
prevention of diabetes and neurological disorders (neurodegeneration), as
well as the reduction of oxidative stress in the central nervous system, have
proved the antidiabetic and neuroprotective properties (CNS) of seaweed
biocompounds. Seaweed-based antidiabetic and neuroprotective com-
pounds, on the other hand, are still in their infancy, and more studies and
discoveries are needed in this field [6].
2.3 Microalgae with Potential for Obtaining

Bioactive Compounds
Because microalgae are such a varied group of heterogeneous microorgan-
isms with such a vast range of coloration, shapes, and cell features, the
issue of marine biotechnology involves their manipulation as well as the
modification of other microbes [3]. Microalgae species are in the hun-
dreds, and only a tiny proportion of those are known to exist in collections
throughout the globe, and only a few hundred of them are believed to have
been studied for the presence of chemicals in the algae’s biomass. Only a
handful of these plants are commercially produced in large quantities [10].
They have potential applications in a range of biotechnological industries
because of their undiscovered diversity, including the production of bio-
chemicals used in food, medicine, cosmetics, and pharmaceutical products
as well as the energy industry [11].
Microalgae are a naturally occurring source of biologically active com-
pounds that have a wide range of potential uses in a variety of fields. These
compounds have piqued the interest of both academia and industry in
recent years, owing to their potential applications in a variety of life sci-
ence disciplines. Their uses range from biomass production for food and
feed to the manufacture of bioactive chemicals for use in the medical and
pharmaceutical industries [10]. Because of the wide diversity of microalgae
available and recent developments in genetic engineering, this group of
microorganisms is one of the most promising sources of new commodities
and applications [3].
As autotrophic microorganisms, microalgae are capable of developing

and synthesizing biocompounds with high aggregated nutritional value
and therapeutic functions. These biocompounds include lipids, proteins,
carbohydrates, pigments, and polymers, all of which are derived from
light energy and inorganic nutrients (carbon dioxide, nitrogen, phospho-
rus, etc.). Recently discovered microalgae may produce a wide range of
Table 2.1 The most important bioactive chemicals derived from microalgae [3].
Microalgae Bioactive compounds
Spirulina sp. Polysaccharides
Spirulina platensis Phycocyanin, C-phycocyanin, Phenolic acids,
tocopherols (vitamin E), neophytadiene,
phytol, PUFAs (n-3) fatty acids, oleic acid,
linolenic acid, palmitoleic acid
Spirulina fusiformis Diacylglycerols
Haematococcus pluvialis Astaxanthin, lutein, zeaxanthin, canthaxanthin,
lutein, β-carotene, oleic acid
Chlorella sp. Carotenoids, sulfated polysaccharides, sterols,
PUFAs (n-3) fatty acids
Chlorella vulgaris Canthaxanthin, astaxanthin, peptide, oleic acid
Chlorella minutissima Eicosapentaenoic acid (EPA)
Chlorella ellipsoidea Zeaxanthin, violaxanthin
Dunaliella salina trans-β-carotene, cis-β-carotene, β-carotene,
oleic acid, linolenic acid, palmitic acid
Dunaliella Diacylglycerols
Botryococcus braunii Linear alkadienes (C25, C27, C29, and C31),
triene (C29)
Chlorella zofingiensis Astaxanthin
Chlorella protothecoides Lutein, zeaxanthin, canthaxanthin
Chlorella pyrenoidosa Lutein, sulfated polysaccharide
Nostoc linckia and Nostoc Borophycin
spongiaeforme
Nostoc sp. Cryptophycin
chemical substances with varying biological activities, including carot-

enoids, phycobilins, polyunsaturated fatty acids, proteins, polysaccharides,
vitamins, and sterols. Carotenoids and phycobilins are phytochemicals that
have biological activity [3, 12].
Microalgal components have been shown to have antimicrobial, antiviral,
anticoagulant, antienzymatic, antioxidant, antifungal, anti-inflammatory,
and anticancer activities, among other qualities [3]. The most important
bioactive chemicals derived from microalgae are listed in Table 2.1 [3].
2.3.1 Spirulina
Spirulina is a member of the Cyanophyta (prokaryotic cyanobacteria) that
first appeared more than three million years ago, resulting in the formation
of the current oxygen atmosphere. Spirulina (Arthrospira) has played an
important part in the management of the planetary biosphere. A GRAS
(generally recognized as safe) accreditation was granted to spirulina by the
FDA (Food and Drug Administration) in 1981 [13]. According to the FDA,
spirulina can be lawfully sold as a food or food supplement without com-
promising human health [14].
Spirulina contains significant amounts of essential polyunsaturated
fatty acids and phenolic compounds, as well as high protein content and
digestibility, making it a nutritious addition to any diet [15]. As a result
of characteristics such as its high nutritional value and the presence of
active biocompounds, this microbe is one of the most extensively exam-
ined microalgae on the planet. Table 2.2 shows the bioactive compounds
extracted from Spirulina. Spirulina is a green leafy vegetable with a protein
content ranging from 50 to 70% (w/w) [3], carbohydrate content from 10 to
20% (w/w), and lipid content from 5 to 10% (w/w). This microalga has high
concentrations of vitamins B1, B2, B12, and E (especially vitamin B12). It
also includes significant amounts of pigments, minerals, and oligo-elements
(between 6 and 9% by dry weight of the biomass), with iron, calcium, mag-
nesium, phosphorus, and potassium being the most abundant. Because of
its antioxidant properties, this microalga has been employed in the produc-
tion of pigments in several research studies throughout the years.
There are several different carotenoids found in Spirulina. These include
β-carotene, tocopherols, phycocyanin, and phycoerythrin. Spirulina also
includes a range of additional components such as tocopherols, phycocy-
anin, and phycoerythrin [16].
Researchers have discovered that cyanobacteria can synthesize intracel-
lular and extracellular compounds that have antibacterial, antifungal, anti-
viral, anticancer, anti-HIV, anti-inflammation, antioxidant, antimalarial,
Table 2.2 Bioactive compounds extracted from Spirulina genus.

Microalga Bioactive compounds Concentration (%, w/w)
Spirulina fusiformis C-phycocyanin 46.0
Spirulina platensis C-phycocyanin 9.6
Spirulina platensis Allophycocyanin 9.5
Spirulina sp. C-phycocyanin 17.5
Spirulina sp. Allophycocyanin 20.0
Spirulina platensis Phenolic 0.71
Spirulina platensis Terpenoids 0.14
Spirulina platensis Alkaloids 3.02
Spirulina maxima Phenolic 1.29
Spirulina maxima Flavonoids 0.46
herbicidal, and immunosuppressive properties, as well as immunosuppres-

sive compounds. The therapeutic potential of Spirulina has been demon-
strated in several research studies. Its applications include the treatment of
hyperlipidemia, cancer, HIV, diabetes, obesity, and hypertension, as well as
the enhancement of immune response in kidney protection against heavy
metals and medications, as well as the lowering of glucose and lipid levels
in the blood. It is also used in the prevention of diabetes and obesity [3].
2.3.2 Chlorella
Spirulina and Chlorella produce between 3,000 and 4,000 tons of micro
algal biomass each year, accounting for the vast majority of the market for
microalgal biomass [17]. In the Chlorophyta family, the eukaryotic genus
Chlorella sp. contains unicellular green microalgae that are eukaryotic [18].
This microalga was discovered by the Japanese, who are accustomed to
eating algae and who use it as a nutritious supplement to enhance their
diet. Chlorella is a superfood that is strong in chlorophyll, proteins, poly-
saccharides, vitamins, minerals, and essential amino acids, amongst other
beneficial compounds. The alga is composed of 53% (w/w) protein, 23%
(w/w) carbohydrate, 9% (w/w) lipids, and 5% (w/w) minerals and oligo-
elements [14].
These nutrient concentrations may be manipulated by manipulating the

culture conditions. This microalga’s biomass also contains a high concen-
tration of B vitamins, notably B12, which are required for the synthesis
and repair of red blood cells. Chlorella, like Spirulina, has received GRAS
certification from the Food and Drug Administration, suggesting that it
may be consumed as food without posing a health risk provided it is grown
in an acceptable environment with adequate sanitation and manufacturing
practices [14, 19].
[Table 2.3 shows the bioactive compounds extracted from Chlorella].
Chlorella contains a variety of bioactive chemicals that have medicinal
properties. Chromolaria has been proven to have cancer-fighting and anti-
coagulant characteristics in experimental studies. It has also been shown
to have antibacterial, antimicrobial, antioxidant, and antihyperlipidemic
capabilities, as well as a hepatoprotective function and immunostimula-
tory activity [3].
Chlorella possesses functional properties that might be ascribed to sev-
eral antioxidant compounds found in the algae. Free radicals have been
demonstrated to be inhibited by antioxidants such as lutein, α-carotene,
β-carotene, ascorbic acid, and α-tocopherol, among other substances.
Some of these compounds are important not just as natural colorants or
additives, but they may also be beneficial in the prevention of cancer and
the treatment of macular degeneration [18, 20].
The most major bioactive element in Chlorella is β-1,3 glucan, which is
a powerful immune stimulant that decreases free radicals and cholesterol
levels in the bloodstream. Gastric ulcers, sores, and constipation have all
Table 2.3 Bioactive compounds extracted from the microalgae of the Chlorella
genus.
Microalga Bioactive compounds Concentration (%, w/w)
Chlorella protothecoides Lutein 4.60
Chlorella zofingiensis Astaxanthin 1.50
Chlorella vulgaris Phenolic 0.20
Chlorella vulgaris Terpenoids 0.09
Chlorella vulgaris Alkanoids 2.45
Chlorella minutissima Phytol 2.70
Chlorella minutissima Phenol 1.81
been proven to be alleviated by the use of this substance. Besides having

anticancer properties, it has also been proven to have prophylactic proper-
ties against atherosclerosis and hypercholesterolemia [21].
2.3.3 Nostoc
Nostoc is a Cyanophyta microalga that forms spherical colonies that
come together as filaments. It is a member of the Nostocaceae family of
Cyanophyta and belongs to the Nostocaceae genus. The filament of this
microalga is made up of heterocysts, each of which has a pattern of homo-
geneous cells and a regular spacing between cells between them [22].
Heterocysts fix nitrogen from the atmosphere to produce amino acids
for microalgal biomass. Heterocysts form in the lack of a nitrogen sup-
ply during microalgal culture, allowing the cells to develop without being
constrained by the nutrient’s limitation [23]. Microalgal biomass from the
Nostoc genus has been used in medicine and as a nutritional supplement
due to its high protein, vitamin, and fatty acid content (Table 2.4). When
this microalga is used to treat fistula and some types of cancer, it proves to
be quite beneficial [24].
Previous studies have shown that biomass is anti-inflammatory and
that it also aids with digestion, blood pressure management, and immune
system stimulation. Several studies have revealed that Nostoc can produce
compounds that are antibacterial, antiviral, and anticancer. Large-scale
Table 2.4 Bioactive compounds extracted from the Nostoc genus.

Microalga Bioactive compounds Concentration (%)
Nostoc sp. Phycocyanin 20.0 (p/p)
Nostoc muscorum Phenolic 0.61 (p/p)
Nostoc muscorum Terpenoids 0.10 (p/p)
Nostoc muscorum Alkaloids 2.30 (p/p)
Nostoc muscorum Phycobilins 0.0229 (p/v)
Nostoc humifusum Phenolic 0.34 (p/p)
Nostoc humifusum Terpenoids 0.10 (p/p)
Nostoc humifusum Alkaloids 1.65 (p/p)
Nostoc humifusum Phycobilins 0.0031 (p/v)
production has been motivated by these discoveries, and it has enormous

economic potential as a result of its nutritional and therapeutic properties
[25].
It has been demonstrated that cyanovirin, which is a possible protein
molecule produced by the Nostoc microalga, is useful in the treatment
of HIV and Influenza A (H1N1) [3]. Many essential fatty acids, such as
linoleic, α-linolenic, γ-linolenic, octadecatetraenoic, and eicosapentae-
noic acid, are present in Nostoc, and these polyunsaturated fatty acids
(PUFAs) are found in Nostoc. Because essential fatty acids are precur-
sors of prostaglandins, the pharmaceutical sector has taken an interest
in them [26].
2.3.4 Dunaliella
Dunaliella is a green, unicellular halotolerant microalga that belongs
to the Chlorophyceae family. This microalga is frequently investigated
because of its ability to withstand harsh environmental conditions, its
physiological characteristics, and the numerous biotechnological uses it
has. For example, Dunaliella is an excellent source of carotenoids, glyc-
erol, lipids, and several other useful substances, such as enzymes and
vitamins [27, 28]. Table 2.5 shows the bioactive compounds extracted
from Dunaliella.
When grown in settings with high salinity, light, and temperature, as well
as nutrition limitation, this microalga may generate up to 14% of its dry
weight in natural β-carotene [29]. Furthermore, in addition to β-carotene,
Table 2.5 Bioactive compounds extracted from

the microalgae of the Dunaliella genus.
Microalga Bioactive compounds
Dunaliella salina β-Carotene
Dunaliella salina All-trans-β-carotene
Dunaliella salina All-trans-zeaxanthin
Dunaliella salina All-trans-lutein
Dunaliella tertiolecta Sterols
Dunaliella salina Sterols
microalga is high in protein and essential fatty acids, and is considered safe
to ingest as indicated by its GRAS designation [14].
A variety of biological activities are exhibited by the compounds
found in the Dunaliella biomass, including antioxidant, antihyperten-
sive, bronchodilatory, analgesic, muscle relaxant, hepatoprotective, and
antiedemal effects. Microalgal biomass can also be employed directly
in food and medicinal formulations, as well as in other applications
[14, 30].
Researchers Chang and colleagues discovered that Dunaliella cells con-
tained antibiotic compounds. According to these researchers, the crude
extract of this microalga significantly prevented the development of bac-
teria such as Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, and
Enterobacter aerogenes, among others. Dunaliella microalga was shown to
have antibacterial action against a variety of pathogens that are import-
ant to the food industry, including Escherichia coli, Staphylococcus aureus,
Candida albicans, and Aspergillus niger, according to another investigation
[28, 31].
Under optimum growth conditions, Dunaliella may be pushed to create
roughly 400 mg of β-carotene per square meter of growing area, which is
equivalent to approximately 400 mg of vitamin A [3]. The cultivation of
Dunaliella to produce β-carotene has been carried out in several countries,
including Australia, Israel, the United States of America, and China. Earlier
this year, Pentapharm announced the introduction of a substance derived
from Dunaliella that has a high potential to stimulate cell proliferation and
enhance the energy metabolism of the skin (Basel, Switzerland). New pilot
plants are being built in India, Chile, Mexico, Cuba, Iran, Taiwan, Japan,
Spain, and Kuwait, among others [29].
2.4 Bioactive Compounds from Cyanobacteria

Microalgae have a large number of bioactive chemicals that may be
extracted and used in a variety of applications. As key sources of value-
added chemicals with medicinal and nutritional significance, they have
emerged as important sources of protein. Cyanobacteria or blue-green
algae were once considered to be laboratory curiosities or nuisance agents
in water bodies, but today they are recognized as an important component
of integrated nutrient management in agriculture [32, 33] and as a source
of pigments, vitamins, phycocolloids, immunodiagnostic agents, and ther-
apeutics, as well as a source of biofuel [34, 35].
In recent years, screening methods have been used to find several bio-
active metabolites generated by cyanobacteria and algae. These screening
procedures used target organisms that were not related to the organisms
that the metabolites evolved for. Numerous biological activities and chem-
ical structures of these substances have been discovered, and they have an
impact on a wide variety of biochemical processes within cells (mainly
directed against photosynthetic processes). Chemicals of this type are
probably associated with the management and succession of algal and
bacterial populations, and can operate as natural herbicides or biocontrol
agents in certain situations [36].
A cyanobacterium with algicidal and bactericidal characteristics should
be predicted in light of the co-occurrence of these organisms in aquatic
natural communities, where an inhibitory interaction between producers
and competitors within the same ecosystem has been seen to occur. In
lakes with the presence of cyanobacterial water blooms, Chrost observed
a significant drop in the number of Gram-positive bacteria, and the gen-
eration of antibiotic compounds may be one of the factors contributing
to these phenomena. Natural herbicides are bioactive allelochemicals pro-
duced by cyanobacteria that have been classified as algicides. Because they
are aimed against photosynthesis (photosystem II), they are referred to
as natural herbicides. In both prokaryotic cyanobacteria and eukaryotic
algae, light-dependent activities are unique, and they are therefore logi-
cal targets for a bioactive producing organism while competing with other
similar organisms (the targets) in the same habitat [36].
Many different types of cyanobacteria generate substances that are
typically regarded to be secondary metabolites, which are molecules that
are not required for general metabolism or growth of the organism and
are only found in certain types of cyanobacteria. Cyanobacteria, such as
Microcystis, Anabaena, Nostoc, and Oscillatoria, create a wide range of
secondary metabolites, some of which are toxic to humans. Many key
marine cyanobacterial compounds, including dolastatin, cryptophycin,
and curacin A, have been identified and are now undergoing preclinical
or clinical testing as anticancer medicines. Dolastatin, cryptophycin, and
curacin A are examples of such molecules [37].
Because a large number of secondary metabolites are strong poisons,
they can cause health issues in animals and people when the producer
organisms are found in large numbers in bodies of water. Different com-
pounds, such as cytotoxic (41%), antitumor (13%), antiviral (4%), anti-
biotics (12%), and the remaining 18% activities include antimalarial,
antimycotics, multidrug resistance reversers, antifeedant, herbicides, and
immunosuppressive agents; aside from the immune effect, blue-green
algae have been shown to improve metabolism. Cyanobacterial lipopep-

tides are derived from cyanobacteria [38].
A prolific producer of almost 800 distinct bioactive secondary metabo-
lites, cyanobacteria are a major source of nonribosomal peptide synthetase
(NRPS) or mixed polyketide synthetase (PKS)–NRPS biosynthesis, with
the majority deriving from NRPS biosynthesis [39, 40]. Several studies
have demonstrated that they are effective against viruses and tumors as
well as against bacteria and HIV. In addition, they are used as a food addi-
tive in several countries. Cyanobacteria are a primitive and varied collec-
tion of microorganisms that share traits with both bacteria and algae. They
are a basic but primitive and diverse group of microorganisms that share
characteristics with both bacteria and algae. Their capacity to survive as a
group in a diverse variety of environments has been linked to their distinct
physiological characteristics as well as their strong adaptation ability under
a diverse range of environmental circumstances.
Cyanobacteria have long been known for their ability to produce a wide
range of compounds, including polysaccharides, lipids, and proteins as
well as vitamins and sterols, as well as enzymes, medicines, and other fine
chemicals, and the demand for these compounds is rising. There have been
significant developments in the identification of bioactive chemicals from
cyanobacteria, and their relevance in agriculture and industry has been
reviewed in this compilation. Spirulina platensis, a cyanobacterium, has a
high concentration of nutrients such as proteins, vitamins, minerals, carbs,
and linolenic acid, among others. It is garnering more and more attention,
not only for its food-related characteristics but also for its potential to be
used in the creation of medicinal products [36].
Hydroperoxy-unsaturated fatty acids, particularly hydroperoxy-linoleic
acid or linolenic acid, have been discovered in algae to be the interme-
diate compound of physiological bioactives that are involved in chemical
defense or wound healing; for example, jasmonic acid, n-hexanal, 2(E) and
3(Z)-nonenal, 2(E) and 3(Z)-hexenal, in contrast to higher plants. Many
bioactive chemicals are produced by Anabaena species, the majority of
which are lipopeptidases with antibacterial, antialgal, anticancer, anti-
inflammatory, cytotoxic, and enzyme-inhibiting properties [36].
Fatty acids, tetraamine, spermine, and piperazine derivatives are pro-
duced by Oscillatoria species, and these compounds have antibacterial
action.
According to some researchers, the Omega-3 fatty acids present in the
oils of some cold-water marine fish are responsible for a reduction in the
prevalence of coronary heart disease. Most likely, these fatty acids come
from plankton in the food chain, which is where they originated. In this
study, several leptosins were isolated from the marine alga Leptosphaeria sp.
and their biological activity was assessed. Of them, leptosin M was found
to be highly hazardous to human cancer cell lines. In vitro and in vivo, the
sulphated polysaccharide of the red microalga Porphyridium sp. has shown
high-order antiviral efficacy against herpes simplex virus (HSV-1 and 2),
indicating that it is a potential therapeutic agent [36].
Phormidium sp., a cyanobacterium, has been shown to impede the
development of a variety of Gram-positive and Gram-negative bacte-
rial strains, yeasts, and fungi, according to research. The same is true for
the plant Lyngbya majuscula, which generates a wide range of chemicals,
including nitrogen-containing compounds, polyketides, lipopeptides,
cyclic peptides, and countless more. This group of chemicals has a wide
range of biological activities, including protein kinase C activators and
tumor promoters, inhibitors of microtubulin assembly, antibacterial and
antifungal agents, and sodium channel blockers.
With each passing year, the number of bioactive chemicals extracted or
synthesized from Nostoc species grows exponentially. Cryptophycins are
anticancer drugs that have been identified from Nostoc strains found in the
wild. Recently, it was discovered that the carbolinium alkaloid nostocarbo-
line (Figure 2.1), which was isolated from the Nostoc plant, functions as a
cholinesterase inhibitor, which is an enzyme that has been targeted in the
treatment of Alzheimer’s disease [36].
Norharmane (Figure 2.2), a chemical derived from the Nodularia har-
veyana plant, has recently been shown to have anti-cyanobacterial activity
C1
–
I
+
N
CH3
N
H
Figure 2.1 Nostocarboline.
N
H
Figure 2.2 Norharman.

against both filamentous and unicellular cyanobacteria and has the poten-
tial to be employed in the prevention of hazardous algal blooms [41].
2.5 Secondary Metabolites from Microalgae

2.5.1 Carotenoids
Microalgae generate a large number of high-value carotenoids [42], which
are the most diversified and widely distributed pigments, and are often
tinted yellow, orange, or red [43]. Carotenoids are a class of terpenoid pig-
ments that are derived from a 40-carbon polyene chain, which is consid-
ered to be their molecular backbone. This molecular backbone provides
the carotenoids with a unique molecular structure as well as the associ-
ated chemical properties, which include light-absorption features that are
essential for photosynthesis, to which they are linked. According to their
structural characteristics, carotenoids are divided into two groups: xan-
thophylls or oxycarotenoids (such as astaxanthin [H. pluvialis], zeaxanthin
[P. cruentum], and others) and carotenes (α- and β-carotenes [D. salina],
lutein [C. pyrenoidosa], and lycopene) [44]. Carotenes are compounds that
do not have any substituents (or even oxygen) in their chemical struc-
ture. Whether they are strict hydrocarbon carotenoids, xanthophylls, or
oxycarotenoids, they all include –OH groups (hydroxycarotenoids: zea-
xanthin from P. cruentum, lutein from C. pyrenoidosa), =O groups (keto-
carotenoids: canthaxanthin from C. striolata, echinenone from B. braunii,
S. platensis (astaxanthin from H. pluvialis). Although there are over 400
carotenoids discovered so far, just a few of them on the market: β-carotene,
astaxanthin, and to a lesser degree lutein, lycopene, fucoxanthin, and bixin.
Carotenoids play an important role in human nutrition by reducing the
risk of certain diseases by providing provitamin A and preventing cere-
brovascular and age-related macular degeneration diseases. Carotenoids
are also important in the prevention of cerebrovascular and age-related
macular degeneration diseases. It has also been established that pigments,
including astaxanthin, β-carotene, lutein, neoxanthin, and zeaxanthin,
have scavenging properties, with astaxanthin claiming to have the greatest
impact of all the carotenoids studied [45].
2.5.1.1 β-Carotene
Three primary microalgae species are needed to produce β-carotene (also
known as β, β-carotene): Dunaliella, Spirulina maxima, and Haematococcus.
It has been employed in a variety of food and beverage items, and is one of
the most widely used food colorants on the market. Animal feed has also
benefited from the inclusion of beta-carotene as a source of vitamin A. The
intestinal enzyme β-carotene 15,15′-monooxygenase catalyzes the conver-
sion of provitamin A carotenoids to retinal, which is essential for vision.
As previously observed, absorption of β-carotene-1 decreases the chance
of developing age-related macular degeneration (AMD) (Table 2.6). In
the health sector, natural β-carotene is chosen over synthetic β-carotene
because it has a blend of cis and trans isomers, the latter of which has anti-
cancer potential [42, 44].
The demand for β-carotene as a pro-vitamin A (retinol) in multivita-
min formulations has risen significantly in recent years [44, 46]. The anti-
oxidant β-carotene can quench singlet oxygen (1O2*) by electron energy
transfer. It can also help to prevent eye disorders such as cataracts and
night blindness from developing. Furthermore, β-carotene prevented
the nuclear translocation of the NF-kB p65 protein component as well as
Table 2.6 Carotenoids from microalgae [42].

Carotenoids Source Therapeutic Activities
β-carotene D. salina Antioxidant, Provitamin A, Age-
related macular degeneration
(AMD), Liver fibrosis,
anti-inflammatory
Astaxanthin H. pluvialis, C. Antitumoral, anti-oxidant,
zofigiensis, C. Vulgaris anti-inflammatory
Lutein D. salina, C. Age-related macular degeneration
pyrenoidosa, C. (AMD), Atherosclerosis, retinal
protothecoids neural damage
Zeaxanthin D. salina, P. cruentum, Antioxidant, Maculopathy,
C. protothtcoids cataracts, anti-inflammatory
Violaxanthin D. tertiolecta, C. Anti-inflammatory, anti-cancer
ellipsoidea
Fucoxanthin P. tricornutum Antioxidant, anti-inflammatory,
anti-cancer
IkBa phosphorylation and degradation, which resulted in the inhibition

of inflammatory cytokines when administered both in vivo and in vitro.
β-carotene has been used to treat a variety of conditions, including asthma,
cardiovascular disease, and erythropoietic protoporphyria. It has also been
shown to lower the chance of developing a variety of malignancies, includ-
ing breast cancer and lung cancer. As it turns out, feeding DO11.1.0 mice
with both additional β-carotene-1 and vitamin E increases the activity of
Th1 cells in their spleen cells, which is a good thing. It was shown that oral
administration of β-carotene-1 to BALB/c mice that had been inoculated
with OVA reduced the titer of specific IgE and IgG1 antibodies and inhib-
ited the antigen-induced anaphylactic reaction by reducing blood hista-
mine levels [42].
2.5.1.2 Astaxanthin
The chemical formula of Astaxanthin is C40H52O4. Although both natural
and synthetic astaxanthin exists, the natural astaxanthin is mostly found in
esterified form, whilst the synthetic equivalent is found in free form [47].
It is derived from Haematococcus pluvialis, Chlorella zofingiensis, Chlorella
vulgaris, and Chlorococcum sp., which are the most important sources of
astaxanthin. The levels gathered by the green alga H. pluvialis outstrip
those collected by any other known source, amounting to up to 4–5% of
dry weight in some cases. Due to its superior antitumor activity compared
to β-carotene and other carotenoids, the red pigment astaxanthin pro-
duced by microalgae has attracted considerable attention. Astaxanthin is
a carotene derivative that is more potent than β-carotene and other carot-
enoids [42].
The pigment Astaxanthin is responsible for the pinkish look of aquatic
fish and shrimp, as well as the color of their skin. It displays several-fold
greater effective antioxidant activity than carotene and vitamin E, mak-
ing it the most powerful antioxidant among the carotenoids in this cat-
egory. The combination of astaxanthin with vitamin C may also have a
synergistic impact, recharging astaxanthin after it has scavenged ROS
via its terminal rings, which appears to be the last scavenger of ROS.
Astaxanthin-2 supplementation has been shown to have anticancer
effects in the post-initiation phase of carcinogen-induced colon and oral
cancer models, respectively. When used with aspirin, it has the potential
to increase antibody production, anti-aging, sun-protective, and anti-
inflammatory properties. It reduces the oxidation of low-density
lipoprotein (LDL) cholesterol while increasing the production of high-

density lipoprotein (HDL) cholesterol and adiponectin. The 3S,3′S geo-
metrical isomer of astaxanthin was shown to be more readily absorbed
than the other geometrical isomers, even though it is found in lower con-
centrations in a racemic mixture [48].
2.5.1.3 Zeaxanthin and Lutein

Microalgae are an important source of the antioxidants zeaxanthin and
lutein, which exist naturally in the environment. D. salina, C. prototh-
ecosis, and Spirulina are the primary sources of lutein and zeaxanthin,
respectively. In addition, two more bioproducts, namely, lutein-3 and
zeaxanthin, are becoming increasingly essential in the nutraceutical sec-
tor as time passes [42, 43]. The yellow xanthophylls or oxycarotenoid
lutein has two cyclic end groups (one β-ionone ring and one ɛ-ionone
ring) that are responsible for its color. Zeaxanthin-4, which is structur-
ally similar to lutein and accumulates in the central retina, on the other
hand, is structurally distinct. In conclusion, evidence from epidemio-
logical and intervention studies using lutein and zeaxanthin supports
the notion that nutrients and health are linked in the prevention of age-
related cataracts and maculopathy. Two lutein-containing products,
Aztec Marigold and Tagetes, have recently been introduced to the market
in the United States [42].
Lutein-3 is useful as a pigment in animal tissue (for coloring chicken
skin and egg yolks), as a food coloring (for coloring egg yolks), cos-
metics, and medicinal items since it has a high nutritional value and
a low toxicity level [49]. Some studies have found that lutein has anti-
inflammatory properties against endotoxin-induced uveitis (EIU)
by inhibiting Ik-degradation and the subsequent production of pro-
inflammatory mediators such as NO, TNF-α, IL-6, PGE2, MCP-1, and
MIP-2. Both zeaxanthin and lutein have been shown to have a signif-
icant role in the maintenance of normal visual function in laboratory
animals [50]. Given that these organs are particularly vulnerable to oxi-
dative damage, lutein and zeaxanthin shield the eyes from the effects of
antioxidants, a fact that makes them extremely useful substances [51].
Oncologists discovered that lutein from the plant C. vulgaris has antican-
cer properties when tested on a human colon cancer cell line (HCT-116)
and that eating lutein-rich foods lowers the chance of developing cancer
[52].
2.5.1.4 Violaxanthin
Violaxanthin is a naturally occurring xanthophyll with an orange color that
may be found in a variety of microalgae. D. tertiolecta and C. ellipsoidea
are two of the most important suppliers of this product. The anti-inflam-
matory properties of violaxanthin isolated from C. ellipsoidea, which were
mediated through regulation of the NF-kB and MAPK pathways, show that
C. ellipsoidea has significant promise as a therapy option for inflammatory
illnesses [42]. Researchers from Soontornchaiboon et al. revealed that the
antioxidant violaxanthin suppressed the generation of NO and PGE2 in
RAW 264.7 cells in a dose-dependent manner. The impact of violaxan-
thin-5 on NO and PGE2 synthesis was similar to the effects of carotenoids,
which have been proven to decrease NO production. For example, β-caro-
tene, lutein, and fucoxanthin have all been found to suppress NO produc-
tion. Furthermore, violaxanthin-5 inhibited the synthesis of PGE2 as well
as the expression of COX-2 at the mRNA and protein levels. Violaxanthin,
an organic natural component that is not synthesized, may thus be a safe
and effective anti-inflammatory drug that might be utilized for medicinal
purposes, according to the researchers [53]. The antioxidant violaxanthin
had a strong anti-proliferative effect on MCF-7 breast cancer cells and gen-
erated biochemical alterations that were characteristic of early apoptosis.
2.5.1.5 Fucoxanthin
Fucoxanthin is a carotenoid pigment with a golden-brown color that was
originally discovered in 1914 and is one of the most abundant carotenoids
found in marine sources [54]. It may be found in a variety of microalgae
classifications, including bacilophytes, bolidophytes, chrysophytes, silico-
flagellates, pinguiophytes, and brown microalgae phaehytes. Bacilophytes
are the most common type of microalgae. Because of its health advan-
tages, such as its anticancer and antiobesity properties, as well as its
anti-inflammatory and antioxidant properties, and its ability to prevent
cerebrovascular illnesses, fucoxanthin is receiving a lot of attention right
now [55, 56]. Additionally, fucoxanthin has been shown in a mouse model
to be harmless, despite its ability to raise the blood levels of both HDL
and non-HDL cholesterol. Several investigations revealed that fucoxan-
thin displayed cytotoxicity against several human colon cancer cell lines
by causing apoptosis and cell cycle arrest in the cells tested. When com-
pared to other carotenoids, it had a greater effect on the viability of colon
cancer cell lines (DLD-1, Caco-2, and HT-29) than the other carotenoids.
Furthermore, fucoxanthin prevented the induction of mouse colon car-
cinogenesis by 1,2-dimethylhydrazine in an in-vivo study. It has also been
claimed that fucoxanthin can block the development of duodenal and skin
cancers, as well as the development of liver tumors in mice. It has been dis-
covered that its anticancer efficacy is mediated by cell cycle arrest, antioxi-
dant activity, and apoptosis induction [55]. In lipopolysaccharide-induced
RAW264.7 macrophages, fucoxanthin-6 prevented the activation of the
nuclear factor-κB (NF-κB) by reducing Iκβ-a degradation and the nuclear
translocation of the p50 and p65 proteins. In vitro, both fucoxanthin and
its metabolite fucoxanthinol displayed antioxidant activity as free radical
scavengers and as a singlet oxygen quencher, demonstrating that they are
powerful antioxidants [56].
2.5.2 Polyunsaturated Fatty Acids

Animals and higher plants do not synthesize polyunsaturated fatty acids
(PUFAs) with more than 18 carbons because the enzymes required for
this process are not present in these species. Microalgae are the principal
producers of polyunsaturated fatty acids (PUFAs) in the oceanic environ-
ment, even though fish oil is the conventional source of PUFAs. More recent
research has concentrated primarily on the synthesis of polyunsaturated
fatty acids (PUFAs), which are employed as nutritional supplements and
medicinal agents. Almost all polyunsaturated fatty acids (PUFAs) derived
from primary producers can be transformed by bioconversions as they go up
the food chain, a process known as trophic upgrading. According to recent
findings, the amounts of essential fatty acids in human diets are associated
with the development of atherosclerosis and coronary heart disease (CHD)
[42]. The presence of omega-3 PUFAs in the brain has been demonstrated
to be important physiological components of the total amount of lipid pres-
ent in the brain, in addition to their beneficial effects against cardiovascular
system disorders and their protective actions against uncontrolled cellu-
lar proliferation. Several neurological activities, such as neurogenesis and
neurotransmission, as well as the protection of the brain against oxidative
stress-induced cerebral damage, rely on omega-3 PUFAs for their survival.
Furthermore, it has been demonstrated that long-chain N-3 PUFAs, such as
docosahexaenoic acid (DHA-8, C22:6n-3) and eicosapentaenoic acid (EPA-
7, C20:5n-3), have significant therapeutic potential for a variety of ailments,
including cancer, atherosclerosis, rheumatoid arthritis, Alzheimer’s dis-
ease, and psoriasis, among others [42]. EPA-7 is critical in the development
and regulation of physiology in humans and higher animals because it is
a precursor to a series of eicosanoids that are key in the development and

regulation of physiology. A class of hormone-like substances known as eico-
sanoids includes thromboxane (TX), prostaglandins (PG), and leukotrienes
(LT), whereas arachidonic acid (AA, 20:4 N-6) and EPA are precursors of
eicosanoid compounds. TX is a hormone-like substance produced by the
body. The omega-3 fatty acids EPA-7 and DHA-8 have been shown to lower
circulating levels of CRP, TNF-α, IL-6, and IL-1, suggesting that they may be
involved in anti-inflammatory activities. The administration of C. vulgaris
extracts orally to tumor-bearing mice resulted in a considerable increase
in phagocyte generation and quality, resulting in significantly longer life.
PUFAs have a vital function in the fluidity of membranes, cellular metabo-
lism, transport, and as precursors of eicosanoid receptors. In the 1980s, fish
oil was the most important source of polyunsaturated fatty acids (PUFAs).
The depletion of fish supplies and contamination of fish have prompted the
usage of other sources of protein [42].
2.5.3 Proteins and Polypeptides

The use of algae as an alternative nutritional source goes back to World
War II when the ingestion of microalgae and seaweeds became more pop-
ular as a means of overcoming dietary protein deficiency [57]. Microalgae
are regarded as prospective sources for the creation of both elementary
proteins and therapeutic peptides and proteins because of their high pro-
tein content. These algal proteins are of good quality and equivalent in
nutritional value to traditional vegetable proteins, according to extensive
analysis and nutritional studies. Arthrospira, Chlorella, and D. salina have
all been used in human nutrition meals as a result of their high protein
content and nutritional value, respectively. Spirulina cells have a great
nutritional value as well as a high digestibility, owing to their high protein
content and the abundance of minerals they contain. All 20 proteinogenic
amino acids are synthesized by microalgae, which means they can be
used as a novel supply of necessary amino acids for human nutrition. The
development of recombinant DNA and hybridoma technologies made it
feasible to generate huge quantities of proteins that behave as medica-
tions, which are referred to as drugs, biologics, or biopharmaceuticals, in
a controlled environment (BFs). Previous studies have found that possi-
ble vaccine candidates have been created by viruses and bacteria, as well
as by malaria and other communicable illnesses, or that they have been
explored for nonviral diseases in the laboratory. Researchers have discov-
ered that phycobiliproteins from marine cyanobacteria and red algae are
capable of exhibiting anticancer, anti-inflammatory, immunomodulatory,
antioxidant, hepatoprotective, and neuroprotective properties [42]. When

compared to the limited secondary metabolites generated by ribosomal
proteins, cyanobacterial polyketide synthase (PKS) and nonribosomal
peptide synthase (NRPS) create a wide variety of bioactive secondary
metabolites that are beneficial to the host. The hybrid polyketide-poly-
peptide structural class of molecules is distinguished by several distinctive
structural characteristics, including the integration of modified amino/
hydroxyl acids, heteroaromatic ring systems, and polyketide-derived
units with extended lengths. The extended polyketide-derived units can
be either linear or undergo cyclization to produce a common scaffold,
such as the pyrrolidone rings in the Jamaicamides, which serve as a scaf-
fold for other compounds. For example, a unit of acetate is employed in
the extension of several amino acids, such as Gly, Phe, Pro, and Ala, to
make them longer. Apratoxin A-45 is a mixed peptide–polyketide natu-
ral product derived from the polyketide synthase/nonribosomal peptide
synthase pathway of the cyanobacterial secondary metabolite. It is a cyto-
toxin that is derived from the apratoxin family of toxins. This cytotoxin is
well-known for its ability to cause cell cycle arrest in the G1 phase as well
as apoptosis [58, 59].
2.6 Biomass of Microalgae

The large-scale production of algal biomass is crucial for a variety of busi-
nesses. With the evolution of technology in this field, a variety of ways for
developing microalgae-based products and downstream processes have
been developed [60].
2.6.1 Biomass Production

Cultivation, harvesting, and biomass dehydration are all steps in the devel-
opment of microalgae biomass, and each one is important.
2.6.1.1 Cultivation
The open-pond and closed-photobioreactor (PBR) technologies have been
developed for the production or cultivation of algal biomass in a controlled
environment. Waterways found naturally in the environment (ponds,
lakes, and lagoons) and man-made ponds are the two forms of open pond
production available (circular and raceway). In comparison to the PBR,
the open pond is a less costly method of producing significant amounts of
algal biomass on a large scale. When it comes to manufacturing, the PBR

system provides a good and well-controlled closed culture system that pre-
vents contamination by molds, bacteria, protozoa, and other microalgae.
To make use of the free energy sources given by the sun, it is usually put
outside. PBR is available in three configurations: tubular (TPBR), vertical
column (VCPBR), and flat-plate PBR (FP-PBR) [60].
2.6.1.2 Harvesting
To separate microalga biomass from the culture medium or harvest it, four
procedures are used: biomass aggregation (flocculation and ultrasonica-
tion), flotation, centrifugation, and filtering. Combinations of two or more
techniques are occasionally used to increase the efficacy of a single strategy.
The microalgae harvesting process is influenced by a variety of elements,
including the density of the algae, their size, and the final products that are
required.
a) Biomass aggregation: The flocculation technique, which

involves adding flocculants to the medium, such as multi-
valent cations and cationic polymers, to aid in neutralizing
the cells’ surface charge, is used to aggregate microalgae
cells together to create a bigger particle known as a floc.
The two types of flocculating agents are chemical floccu-
lants and biological flocculants. Iron and aluminum salts
are widely used as chemical flocculants because they are
inexpensive and easily accessible. Acrylic acid and chitosan
are two biopolymer bioflocculants that are often used in
industry. The use of ultrasonic technology facilitates the
harvesting of algal biomass by causing aggregation, which is
followed by improved sedimentation. As a result of the fact
that ultrasonic harvesting does not generate shear stress on
the biomass even though it is used continuously, the valu-
able metabolites are kept [60].
b) Flotation: Micro-air bubble disperser technology is a tech-
nique that uses a micro-air bubble disperser to float algal
cells on the water’s surface without the use of chemicals. It
is cost-effective to use this technology because it has low
operating expenses, a simple operating method, and a high
biomass collection rate.
c) Centrifugation: It is the recovery of algal biomass from
culture media by the use of gravitational force, which is
accomplished by the use of a centrifuge. Because of the sig-

nificant energy input and the need for continual mainte-
nance, this process is quick, easy, and effective; but the cost
can soon escalate. When a substantial gravitational force
is applied, this method produces internal cell damage that
results in the loss of essential nutrients, which is another
issue with this method.
d) Filtration: A technique for isolating algal biomass from a
liquid culture medium that involves the use of a porous
membrane with varying particle sizes is described here.
Conventional, microfiltration and ultrafiltration are the
three procedures that may be used to put it into action (iso-
lation of metabolites). Small size microalgae (>70 μm) such
as Coelastrum and Spirulina are collected by the use of con-
ventional filtering methods. To capture microalgae that are
smaller than a bacterium, microfiltration and ultrafiltration
are employed in conjunction with each other [60].
2.6.1.3 Biomass Dehydration

Algae biomass is processed to the next phase as soon as it is removed from
the growth medium to minimize rotting or prolong the shelf-life of the
biomass. The three most popular types of drying or dehydration proce-
dures are sun-drying, spray-drying, and freeze-drying. The following are
the final elements on which the strategy will be based:
a) Sun-drying: This is the traditional method of lowering the

moisture content of paddy that involves laying the grains
out under the sun to dry them. When the grains are exposed
to solar radiation, they become hotter as well as warmer
than the surrounding air, increasing the rate at which water
evaporates off the grains [61].
Sun drying, on the other hand, is typically labor-
intensive and has a limited capacity. With this approach, it
is also difficult to maintain temperature control, and grains
can quickly get overheated, resulting in cracked grains and
poor milling quality. At night or during heavy rain, it is also
impossible to dry by the sun. The cost of this approach is the
least expensive when compared to the other two options on
the table. This approach relies solely on solar energy, which
has downsides in terms of weather conditions, long drying
times, and the amount of drying space that must be set aside
for drying. Microalgae drying in the sun is an unpredictable
process, and as a result, overheating may occur along with
alterations in texture, color, and flavor.
b) Spray-drying: This is a technique for rapidly drying a liquid
or slurry into a dry powder by using a hot gas to acceler-
ate the drying process. Heat-sensitive things, such as foods
and medicines, or items that require a highly consistent
and small particle size are among the items for which this
method of drying is preferred [62]. In most cases, the air is
used as the heated drying medium; however, nitrogen may
be used in the case of flammable liquids, such as ethanol, or
in the case of products that are sensitive to oxygen. It is well-
known that spray-drying is a method of particle manufac-
turing that entails the transformation of a fluid substance
into dried particles by making use of a gaseous hot drying
medium. Spray-drying has significant advantages in the
manufacture of medical devices, as demonstrated below. In
reality, the creation of microspheres and microcapsules for
use in drug delivery systems is a very typical occurrence
[62]. A thin spray of suspension droplets in continuous con-
tact with hot air in a large vessel is used to create dry powder
in this process, which is similar to the previous one. There
are various advantages to using this technology, including
the capacity to operate continuously, the fineness of the
powder produced, and the ability to retain a high-quality
product by drying it quickly after production. Even though
some algal constituents, such as pigments, may deteriorate
substantially over time, and the technique is expensive, this
technology is frequently utilized for high-value operations
because of its efficiency [62].
c) Freeze-drying or Lyophilization: Using a vacuum to remove
any water or other solvents from a completely frozen sam-
ple, the ice can transition straight from a solid-state to a
vapor state without passing through a liquid state [63]. This
method of drying microalgae is only employed in the labo-
ratory due to the high expense of large-scale manufacture.
Freeze-drying is a direct dehydration process for frozen
materials that uses sublimation to accomplish dehydration.
Before freeze-drying, the microalgae are frozen to solidify
the material contained therein. Low temperatures are used
to gradually reduce the moisture content of the microalgae,

while still maintaining the product’s firm structure and
high quality [63].
2.6.1.4 Extraction of Bioactive Compounds

Microalgae are made up of a range of different components, including car-
bohydrates, lipids, proteins, minerals, and a variety of other substances.
The algal biomass will be pretreated to release the bioactive component
that has been stored in the cells. This bioactive component will be used
for a variety of purposes, including biofuels/energy production and agri-
cultural use. Several methods, including physical, mechanical (bead mill-
ing, homogenization, microwave, ultrasonic, and pulsed electric field) and
chemical (solvent, acid, and alkali) lysis, as well as biological extraction,
will be used to lyse the cell walls and extract the essential components
(enzymes). The pretreatment procedure that is utilized is dictated by the
final goods that are intended to be produced [60].
2.7 Pharmaceutical Applications of Microalgae

In addition to being a source of bioactive components, microalgae have the
potential to be employed in medicinal formulations.
A large number of studies have demonstrated that microalgae com-
pounds are beneficial in the prevention and treatment of diseases such as
diabetes, obesity, cardiovascular disease, cancer, inflammation, Alzheimer’s
disease, depression, and bacterial, fungal, and viral infections. Despite
this, there are currently just a handful of microalgae with pharmacologi-
cal potential that have been identified. Because of limited extraction yields
and high production costs, the commercialization of several microalgae-
derived bioactives has been delayed. Furthermore, several microalgae
species have the potential to induce major side effects, such as allergic
reactions and the accumulation of heavy metals and toxins. Microalgae-
derived purified compounds and enriched extracts for approval and com-
mercialization require a strong emphasis on good manufacturing practices
in cultivation, harvesting, extraction, and purification, as well as controls
to limit toxins and impurities. This is especially true for the production of
enriched extracts.
a) Cardioprotective properties: The cardioprotective bene-

fits of several microalgae-derived compounds have been
investigated. Antioxidant properties of carotenoids have

been demonstrated, and these properties are critical in
preventing cell damage caused by free radicals, which have
been associated with chronic cardiovascular disease and
stroke. There has been some research on the cardioprotec-
tive properties of certain microalgae that generate a large
number of carotenoids in this area. For example, D. salina
microalgae may produce up to 10–13% β-carotene, which is
protective against atherosclerosis in both rats and humans
in laboratory studies.
Polyunsaturated fatty acids (PUFAs), notably omega-3
fatty acids, such as DHA, EPA, and α-linoleic acid (ALA),
are another kind of bioactive having cardioprotective
properties. DHA and EPA are particularly beneficial in
this regard. It has been demonstrated that they can reduce
blood cholesterol levels and improve hypertension. DHA is
the only PUFA that is now commercially available among
these fatty acids. It is currently prohibitively expensive to
synthesize purified EPA obtained from various microalgae,
such as Porphyridium purpureum and Isochrysis galbana,
for commercial use [60].
b) Anticancer properties: In recent years, there has been a sig-
nificant amount of research on the anticancer potential of
bioactives derived from microalgae. Microalgae pigments,
such as astaxanthin, beta-carotene, lutein, violaxanthin,
and fucoxanthin, have the greatest potential to be mar-
keted as medicines due to their established uses as nutra-
ceuticals and cosmetics, as well as increased demand for
dietary supplements. Astaxanthin is the most widely stud-
ied microalgae pigment. While astaxanthin and β-carotene
are already commercially produced from the microalgae
Dunaliella salina and Haematococcus pluvialis, other carot-
enoids such as lutein and fucoxanthin are gaining popu-
larity. It has been discovered that the diatom microalgae
Phaeodactylum tricornutum, which is grown in a pilot-scale
photobioreactor and can be considered a commercially via-
ble source of fucoxanthin, can be used to extract fucoxan-
thin. Fucoxanthin has been extracted from these algae and
is a commercially viable source of fucoxanthin [60].
β-carotene: Astaxanthin and β-carotene are produced by
Dunaliella and Haematococcus, respectively, which are both
important sources of carotenoids in the environment. Using

human colon cancer cell lines, revealed that β -carotene pig-
ments significantly reduced the multiplication of the cells
[15].
Astaxanthin: The microalgae Haematococcus pluvialis,
Chlorella zofingiensis, and Chlorococcum sp. are the primary
sources of astaxanthin in the environment. Palozza et al.
investigated the effect of astaxanthin in the development of
cell lines and discovered that this carotenoid can suppress
the proliferation of human CRC (colorectal cancer) cell
lines, which was previously unknown.
Astaxanthin, lutein, and zeaxanthin were shown to be
the most effective carotenoids for preventing cell prolif-
eration. The antioxidant astaxanthin has been proven in
multiple studies to have an inhibitory impact on apopto-
sis (programmed cell death). As a result, astaxanthin gen-
erated from microalgae has gained popularity and should
be an excellent choice for both cancer prevention and
chemotherapy.
Lutein: In general, dietary carotenoid consumption,
particularly lutein consumption, is thought to be associ-
ated with a lower risk of developing a variety of malignan-
cies (colon, lung, and breast). Lithium-containing algae
Dunaliella salina, Chlorella sorokiniana, and Chlorella
protothecoides are the primary producers of lutein, which
has been shown to have an antiproliferative impact on the
human colon cell line HCT-116 in studies. Low doses of
dietary lutein (0.002% and 0.02%) have also been shown to
be effective in preventing the development of breast cancer
[60].
Fucoxanthin: For cancer prevention, the carotenoid
fucoxanthin is the most promising of the carotenoid fam-
ily of pigments. Cancer cells (Caco-2, HT29, and DLD-1),
prostate cancer PC-3 cells, and HL-60 leukemia cells were
all shown to have antiproliferative properties when the
compounds were tested. The antioxidant fucoxanthin is
showing tremendous promise as a cancer-fighting agent as
a result of these findings [64].
Fucoxanthin is rapidly gaining popularity as a result
of its numerous health benefits, which include cancer
prevention, weight reduction, anti-inflammatory prop-

erties, antioxidant properties, and the prevention of
cerebrovascular disease. It has been demonstrated that
fucoxanthin is harmless in a mouse model and that it also
increases levels of both HDL and non-HDL cholesterol in
the bloodstream [60].
Phycobiliproteins: Scientists have discovered that phyco-
biliproteins, which are pigments present in red algae and
cyanobacteria, have advantageous fluorescence qualities.
A few examples of common phycobiliproteins are phyco-
erythrin (PE), phycocyanin (PC), and allophycocyanin
(APC). This group of pigments is composed of hetero-
oligomers that are grouped into complexes known as “phy-
cobilisomes” within the producing cells (Cyanophyta) or
chloroplasts (Rhodophyta) of the cells that generate the
pigments.
Long used as natural colors, phytobiliproteins are now
widely used in nutraceuticals and other biotechnological
applications, as well as in cosmetics products [65].
Another possible anticancer medicine is phycocyanin,
a protein pigment that belongs to the phycobiliprotein
family of proteins. Scientists have recovered phycocyanins
from the microalgae Spirulina platensis, which is used in
commercial production, but they have also recovered them
from other cyanobacteria, including Limnothrix sp.
c) Antiviral properties: Microalgae may potentially include
bioactives with antiviral action, which are yet to be discov-
ered. For example, antiviral lectin proteins such as cyano-
virin (CV-N) and scytovirin (SVN) have been identified
to work against viruses. Cyclic peptides are also known to
have antiviral properties [60].
d) Antimicrobial properties: The emergence of antibiotic resis-
tance in humans as a result of the widespread use of anti-
biotics in clinical practice highlights the urgent need for
the discovery of new antibacterial compounds. Microalgae
contain antibiotics that have a broad and efficient antibacte-
rial action against a variety of microorganisms. The antimi-
crobial activity of these bacteria is enhanced by their ability
to produce substances such as polyunsaturated fatty acids,
acetogenins, halogenated aliphatic compounds, terpenoids,
sterols, sulfur-containing heterocyclic compounds, car-

bohydrates, terpenoids, sterols, and halogenated aliphatic
compounds [3].
The amount of fat present in microalgae extracts has an
impact on their antibacterial efficacy. Due to their capac-
ity to produce compounds such as α- and β-ionone and β-
cyclocitral, as well as neophytadiene and phytol, microal-
gae have demonstrated significant antibacterial activity. The
antimicrobial activity of microalgae against human patho-
gens such as E. coli, Pseudomonas aeruginosa, Staphylococcus
aureus, and Staphylococcus epidermidis has been related to
several fatty acids, including γ-linolenic acid, eicosapen-
taenoic acid, hexadecatrienoic acid, docosahexaenoic acid,
and palmitoleic acid [60].
e) Anti-inflammatory properties: As a protective mechanism
against acute infections, inflammation is essential because
it allows invading bacteria to be detected and eliminated.
In contrast, if it develops as a chronic and subclinical con-
dition, and if the process is not managed over time, the
active immune system can cause tissue damage and upreg-
ulate chronic disease states such as cardiovascular disease,
Alzheimer’s disease, inflammatory bowel disease, and obe-
sity, among others [42].
The anti-inflammatory activities of many bioactive com-
pounds produced from marine life have been proved to be
potent and mechanistically intriguing, and marine cyano-
bacteria play a crucial part in the production of this class
of molecules (for instance, anti-inflammatory bis-bromo
indoles from Rivularia sp.). Micro-algal phytosterols and
their secondary metabolites are potential anti-inflammatory
medicines, and the synergistic effect of these compounds
should be taken into consideration while optimizing their
respective roles. Phospholipid polysaccharides, which have
a pharmacological effect such as anti-inflammatory or
immunomodulating qualities, are generated by algae such
as Phaeodactylum, Porphyridium, and C. stigmatophora,
among other species [42].
f) Antioxidant properties: The desire for a natural substance
that is both safe and effective as an antioxidant is increas-
ing across the world. This is due to the rising need for mar-
keted items such as food, medicines, and cosmetics that
reduce oxidative damage to living cells and prevent deg-

radation. This is especially true in the food industry. It is
thought that oxidative damage caused by ROS, such as the
hydroxyl radical (HO•), superoxide anion, and hydrogen
peroxide (H2O2), can cause atherosclerosis, cataracts, mus-
cular dystrophy, rheumatoid arthritis, neurodegeneration,
cancer, and aging. Given the health concerns and hazards
associated with synthetic antioxidants such as butylated
hydroxytoluene (BHT) and propyl gallate (PG), antioxi-
dants derived from natural products are urgently needed.
BHT is an example of such an antioxidant. In their natural
environments, photoautotrophs are subjected to high levels
of oxidative and radical stress, which they must overcome
to survive. In microalgae, antioxidant molecules, such as
carotenoids, phenolic compounds, fatty acids, tocopherol,
flavonoids, and particularly abundant alkaloids, play an
important role in the regulation of the oxidative process
[42].
2.8 Conclusion
Algae can generate natural compounds that have vital biological activities,
which are otherwise unavailable. Natural product research in this subject
is still in its early stages, even though significant research on high-value
compounds obtained from microalgae has been published. Great-value
microalgae compounds are in high demand due to their applicability in
a wide range of industrial applications including pharmaceutical, nutra-
ceutical, cosmeceutical, animal feed, biological waste treatment, and other
fields of science and technology. This chapter discussed the significance
of microalgae as distinct sources of bioactive chemicals and the value of
microalgae as a source of bioactive chemicals. We have utilized the algae-
based chemicals astaxanthin and fucoxanthin as examples of intriguing
algae-based compounds with health and economic promise, and we have
emphasized the immense potential for identifying novel bioactive mole-
cules in microalgae.
Identifying novel compounds with improved activity in newer and older
microalgae species represents a fruitful research approach for advancing
the field of biotechnology in general and biomedical applications in par-
ticular, demonstrating their significant potential for biotechnological and
biomedical applications.
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searchlibrary.com
3
Bioactive Compounds Derived
from Microalgae Showing
Diverse Medicinal Activities
D. Tiwari*, P. Mishra and N. Gupta
Faculty of Pharmacy, RBS Engineering Technical Campus, Bichpuri, Agra, India
Abstract
Many diseases are becoming resistant to drugs. With this in mind, researchers
are searching for cheap and effective drugs for their cure. Cyanobacteria can help
attain this goal.
Biologically active compounds are derived from algae and marine organisms.
These natural compounds possess diverse biological activities like anthelmintic,
antibacterial, antifungal, antimalarial, antiprotozoal, antituberculosis, and antivi-
ral activities. These biologically active compounds are created with a variety of
molecular targets in mind and thus may potentially contribute to several pharma-
cological classes. The synthesis of natural products and their analogues provide
effective structural modifications on the parent compounds, which may be useful
in the discovery of potential new drug molecules with different biological activ-
ities. Natural organisms have developed complex chemical defense systems by
repelling or killing predators, such as insects, microorganisms, animals, etc. These
defense systems have the ability to produce large numbers of diverse compounds
which can be used as new drugs
Cyanobacteria are photosynthetic prokaryotic microorganisms. Since ancient
times, cyanobacteria have been used as food and fodder. However, they are well-
known for producing toxins and fouling ponds, as they form water bloom. Various
studies are currently being done to also prove their potency in medical science.
Their strength is that they produce various metabolites that are antibacterial, anti-
fungal, antimalarial, antitumor, antialgal, antiviral, UV protectants, inhibitors of
enzymes, hepatotoxins and neurotoxins.
77
Keywords: Cyanobacteria, hepatotoxins, prokaryotic
3.1 Introduction
Algae are eukaryote photosynthetic organisms with polyphyletic and para-
phyletic characteristics ranging from unicellular to multicellular. Algae can
be classified into six phyla based on scientific classification: Chrysophyta
(diatoms), Chlorophyta (green algae), Euglenophyta (euglenoids), Phaeo
phyta (brown algae), Pyrrophyta (dinoflagellates), Pyrrophyta (dino-
flagellates), and Rhodophyta (red algae). By using DNA sequencing
technique, algae are classified into ten major phyla: Heterokontophyta,
Glaucophyta, Euglenophyta, Cryptophyta, Haptophyta, Rhodophyta,
Dinophyta, Chlorophyta (green algae) and the prokaryotic Cyanophyta
and Prochlorophyta [1, 2]. Each class of algae is known to produce a broad
range of secondary metabolites with different biological mode of action;
but just a small subset of these compounds has been discovered, screened
and isolated. The rapid growth rate of algae, combined with their exten-
sive spectrum of secondary metabolites, makes them potentially prolific
sources of highly bioactive metabolites. Diverse algae are currently being
used for production of food, pharmaceuticals, cosmetics, fertilizers, and
biofuels [3–5]. Algae are photoautotrophic organisms, either prokaryotic
or eukaryotic, capable of absorbing nitrogen and phosphorus from the
medium into biomass during their growth, and the produced biomass can
subsequently be transformed to various bioproducts following an appo-
site process [6] (Table 3.1). The biochemical composition, specifically the
Table 3.1 Biochemical compounds of microalgae.

Algae Proteins (%) Carbohydrates (%)
Anabaena cylindrica 43–56 25–30
Aphanizomenon flos-aquae 62 23
Chlamydomonas reinhardtii 48 17
C. pyrenoidosa 57 26
C. vulgaris 51–58 12–17
Dunaliella salina 57 32
Dunaliella bioculata 49 4
Diverse Medicinal Activities of Microalgae 79
protein and carbohydrate of microalgae, make them attractive in produc-

ing several value-added compounds. The ratio of biochemical components
or the ratio of proteins/carbohydrates/lipid of algae is species specific. For
example, Spirulina maxima is an excellent source for protein (60–71%
w/w), Porphyridium cruentum is a rich source of carbohydrates (40–60%),
and Scenedesmus dimorphus is 40% lipids [7].
Plants, fruits, and seaweeds have long been used to extract antioxidant
components such as phenolic compounds, pigments, polysaccharides,
and carotenoids [8]. Various techniques, such as the 1,1-diphenyl-2-
picrylhydrazyl radical (DPPH•) scavenging assay, hydroxyl/superoxide
radicals (•OH/O2•) scavenging assay, and ferric chloride scavenging
assay, have been used to validate relative polysaccharides and pigment
compounds as effective antioxidants in ferric-reducing antioxidant power
(FRAP) or lipid peroxidation inhibition capacity assay [9, 10]. A great num-
ber of new efficient natural antioxidants continue to be discovered among
the vastness of marine biotopes. In fact, the marine environment spans at
least three-quarters of the Earth’s surface, and many microbes living on it
have evolved extremely clever growth and adaptation tactics. As a result,
marine creatures provide an unlimited supply of antioxidant biomolecules,
including I enzymes (catalase and superoxide), (ii) exopolysaccharides,
(iii) carotenoids, and (iv) peptides [11, 12]. The constant growth of inter-
national markets asking for more natural antioxidant biomolecules has
to be correlated with the industrial expansion of marine microorganisms
for high scale-up industrial processes to produce better yields of selected
marine antioxidants. Consequently, the goal of this chapter is to provide an
overview of recent developments in the field of antioxidant biomolecules
generated from marine microorganisms, such as bacteria and microalgae,
as well as their present development for potential industrial applications in
nutraceutical, cosmeceutical, and pharmaceutical fields.
Microalgae are known to be excellent sources of pigments, lipids, includ-
ing omega-3 fatty acids, vitamins, toxins and other chemicals [13, 14].
Recent studies have shown that various microalgae may have antiprolifer-
ative and anticancer activities [15]. Key qualities (e.g., easy to culture and
fast-growing) are commonly used to select microalgal strains for poten-
tial biotechnological applications. In addition, when growing a microalga,
numerous elements must be considered, such as suitable circumstances
(e.g., light, temperature, air bubbling, nutrients, salinity, and pH) and the
possible presence of associated bacteria. Algal bioactivity may be owing to
bacterial presence if the strain is not axenic. Isolation and cultivation are
still problematic for a number of species observed in natural samples or
detected in meta-genomics data sets; however, when compared with some
of the other most widely used marine creatures, especially macroorgan-

isms, mass production of microalgal species is easier. They can be mass
cultivated in photobioreactors and have quick generation times (doubling
time of 5–8 h for some species), allowing them to overcome issues related
with overutilization the depletion of marine resources and the adoption
of damaging collection techniques. Moreover, for a large number of spe-
cies, genetic alteration procedures are available to boost their potential as
active chemical sources. The most common pathway for drug discovery
from microalgae includes their culture in small or large volumes (e.g.,
using photobioreactors), pellet concentration (through centrifugation or
filtration), and chemical analysis. Extraction of microalgal pellets can be
done using a variety of methods to locate the desired metabolites [16] and
screening the extracts for different bioactivities (e.g., antioxidant, anti-
inflammatory, antimicrobial and anticancer testing). Bioactivity-guided
fractionation allows the active fraction to be identified, along with the like-
lihood of active compound.
Since marine microalgae are often easier to grow than other micro-
organisms, there is the possibility of obtaining a constant source of marine
natural products (MNPs) to meet the demands of the food, nutraceuti-
cal and cosmeceutical market. They do, in fact, represent a renewable and
underutilized resource for drug discovery.
Aside from the compound discovery pipeline mentioned, other meth-
odologies for microalgae have been employed, such as identifying enzyme
pathways involved for the synthesis of bioactives (through genomics and
transcriptomics analyses “or” proteomics and metabolomics investigations).
To activate production of the largest spectrum of metabolites or enhance
the production of selected ones, microalgae are first cultivated under con-
trol or stressful conditions such as altering light exposure, salinity, or
nutrient content [17, 18]. When the culturing parameters are modified,
a strategy known as “One Strain Many Compounds” (OSMAC), the same
species may produce different metabolites and have diverse bioactivities.
The RNA, DNA, and proteins extracted from the microalgal cells may then
be extensively sequenced and examined with bioinformatics tools in order
to undergo drug discovery with in-silico approaches. In-silico identifica-
tion is then confirmed/implemented by bioactivity screening, heterolo-
gous expression, genetic engineering and/or chemical synthesis in order to
produce higher amounts of the metabolite of interest and meet industrial
demand.
3.2 Microalgae with Anti-Inflammatory Activity

Anti-inflammatory properties were previously found for various marine
diatoms, such as Porosira glacialis, Attheya longicornis [18], Cylindrotheca
closterium, Odontella mobiliensis, Pseudo-nitzschia delicatissima [17] and
Phaeodactylum tricornutum for the dinoflagellate Amphidinium carterae
[19]. Furthermore, the green algae Dunaliella bardawil and Dunaliella
tertiolecta [20] analyzed the release of tumor necrosis factor (TNF), one
of the primary inflammatory effectors [21] in lipopolysaccharide (LPS)-
stimulated monocytic leukemia cells (THP-1). In their study on LPS-
induced RAW macrophages, Samarakoon et al. found that the suppression
of nitric oxide (NO) generation (percent) was a good indicator of anti-
inflammatory efficacy [19].
In a double-blind placebo-controlled randomized clinical trial, sev-
enty patients affected by non-alcoholic fatty liver disease (NAFLD) were
recruited to test the effects of Chlorella vulgaris 300 mg tablets commer-
cially available as Algomed®; the supplements, which contained 98%
C. vulgaris powder, 1% separating agent, and 1% plant-based magnesium
stearate, were used in the experiment. For eight weeks, patients were given
four C. vulgaris pills each day. For patients treated with C. vulgaris, the
pro-inflammatory cytokine TNF-α was found to be substantially lower in
the blood of those who took the supplements [22].
Finally, Lavy et al. showed the protective effects of spray-dried
D. bardawil powder in rats, which inhibited acetic acid-induced small
intestinal inflammation [20], whereas Caroprese et al. demonstrated that a
combination of phytosterols from D. tertiolecta reduced the cytokine pro-
duction in a sheep model of inflammation [23].
With the exception of the final example, nothing is known about the
chemicals responsible for the anti-inflammatory action seen in the trials.
In addition, there are some studies reporting the anti-inflammatory activ-
ity of pure compounds isolated from both marine and freshwater micro
algae: the carotenoids lutein and astaxanthin, and fatty acids.
Ingebrigtsen et al. studied EPA (eicosapentaenoic acid) and DHA (doco-
sahexaenoic acid), as well as sulphated polysaccharides (sPS) [18]; and
Lauritano et al. used an OSMAC (one strain many compounds) approach,
changing culturing condition parameters, such as nutrients, light, and
temperature, in order to trigger anti-inflammatory activity [17]. They dis-
covered that the investigated species were active only under certain cir-
cumstances, emphasizing the necessity of choosing the right parameters
to boost microalgal extract bioactivity. Similarly, they found that chemical
stimuli (e.g., low oxygen, NaCl, and nutritional deprivation) increased the
synthesis of anti-inflammatory molecules (carotenoids, fatty acids, and
sulphated polysaccharides) from some microalgal species (e.g., Chlorella
zofingiensis, Coccomyxa onubensis, Cromochloris zofingiensis, Dunaliella
salina, D. tertiolecta, Haematococcus pluvialis, Nannochloropsis oceanica,
Pavlova lutheri, P. tricornutum, and Spirulina platensis).
3.3 Microalgae with Immunomodulatory Activity

Several microalgae have been shown to exhibit immunomodulatory
activity in humans and other species (e.g., sheep and mice), but the
chemicals that cause this activity are often still unknown. As reported,
dried algae and raw extracts were active against various immune cells.
Cutignano et al. [24] examined raw methanolic extracts and fractions
derived from them (designated A–E) from a variety of microalgal spe-
cies (Alexandrium andersoni FE108, Alexandrium tamarense FE107,
Chaetoceros calcitrans FE20, Chaetoceros socialis FE17, Ditylum bright-
wellii (T. West) Grunow, Dunaliella salina FE209, Skeletonema costatum
RCC1716, S. dohrnii FE82, S. marinoi FE65, S. pseudo-costatum FE25,
Skeletonema sp. KS5 and Thalassiosira weissflogii 1336) on human
peripheral blood mononuclear cells (PBMCs). Immunostimulant activ-
ity in this study was considered as induction of IL-6 in PBMCs cells.
They found that raw methanolic extracts were active for S. costatum
and S. dohrnii. Fractionation allowed for these two species to identify
the active fractions. Triglycerides rich fraction (named fraction E) was
active for S. marinoi. The nucleoside-rich fraction (called fraction B) was
active for S. dohrnii, while the S. pseudo-costatum fraction was inactive.
Fractionation also assisted in the identification of active fractions for
additional species whose raw methanolic extracts were not active. This
is most likely because fractions had less salt (mostly NaCl) than primary
extracts. The glycolipidic and phospholipidic fraction (called fraction
C) was active for A. The nucleosides-rich fraction (called fraction B)
of the tamarense was active for D. Fraction A, which was rich in salina,
ammino acids, and saccharides, the glycolipidic and phospholipidic
fraction (fraction C) and the fraction rich in free fatty acids and sterols
(called fraction D).
Other extracts produced from microalgae have been evaluated for their
immunostimulatory properties. Polysaccharide extracts (aqueous extracts)
from Chlorella stigmatophora were evaluated evaluated in vitro and in vivo
in an animal model study. Specifically, BALB/c mice were injected with
5 mg of polysaccharide extracts per kg of body weight in order to assess

phagocytic activity in vitro and in vivo utilizing macrophages from the
peritoneal cavity. Polysaccharide extracts of 5 mg or 10 mg per kg of body
weight were administered into C57BI mice two days before or after the
injection of sheep red blood cells (SRBC). This experiment was performed
in order to test the activation on SRBC [25]. Polysaccharide extracts from
C. stigmatophora were able to trigger phagocytic activity in macrophages
from the peritoneal cavity in both tests. At 150 g/ml, Euglena gracilis glu-
cans (also known as paramylon) activated NK cells and raised levels of
TNF- and IL-6, two pro-inflammatory mediators of TNF-α and IL-6 [26,
27]. Sulfated exopolysaccharides from Gyrodinium impudicum KG03 (at
0.1–10 g/ml) elicited a cellular response in peritoneal macrophages in
in-vitro mouse models [28] (Table 3.2). Sulphated polysaccharides isolated
from Tribonema sp. have also been discovered to increase macrophage cell
survival and cytokine expression. The authors discovered that cell viability
was only enhanced in the presence of preservatives of 25 µg/mL of sulfated
polysaccharides, while the cytokine expression increased with sulfated
polysaccharide treatment at 12.5–200 µg/mL. Park et al. tested the immu-
nostimulatory activity of Thraustochytriidae sp. on human lymphocyte
B-cells. They discovered that polysaccharides from this alga could stim-
ulate cell proliferation but not cytokine production when tested at 103 to
109 w/v.
The in-vivo immunostimulatory efficacy of Chlorella vulgaris has also
been tested in double-blind placebo-controlled randomized clinical stud-
ies. Sixty participants were selected and allocated to one of two groups:
placebo or chlorella. The active component of the pills tested was dried
C. vulgaris, which was added to the diet of the participants at a rate of 5 g
per day. All of the participants were advised to continue living their nor-
mal lives and eating their normal diets. The NK activity of PBMCs derived
from treated patients was enhanced by a C. vulgaris-supplemented diet,
which also raised blood levels of INF-, IL-1, and IL-12 [29].
Immunostimulatory action has also been linked to microalgae dietary
supplementation. Indeed, feeding mice commercially available spray-
dried preparations of D. salina (369 or 922.5 mg of algal extract per kg
of body weight) enhanced NK and macrophage activation as well as leu-
kemic mouse survival rates [30]. Tetraselmis chuii (50 or 100 g of lyo-
philized alga per kg of dry food) in gilthead seabream (Sparusaurata L)
increased the expression of numerous immune system genes, including
T-cell receptor (TCR) beta, major histocompatibility complex genes,
and IgM. The majority of these chemicals function as vaccine adju-
vants, enhancing immune response by activating APCs [31] (Table 3.2).
Table 3.2 Immunomodulatory chemicals are synthesized or have

immunomodulatory effects in marine microalgae. PBMC stands for human
peripheral blood mononuclear cells, NA stands for not available, and w/v
stands for weight/volume.
Mechanism/
organism
Extract/fraction/ Active and target cells
Microalgae compound concentration (or model)
Alexandrium Total Extract/ NA Activation of
tamarense Fractions IL-6/Human
PBMC
Chaetoceros Fractions NA Activation of
calcitrans IL-6/Human
PBMC
Chaetoceros Total extract NA Activation of
socialis IL-6/Human
PBMC
Chlorella Crude polysaccharide 5 or 10 mg/kg Activation of
stigmatophora extracts phagocytic
activity -
SRBC/Mouse
Chlorella Diet Diet Improvement of
vulgaris supplementation/ supplementation/ NK activity
commercially commercially and serum
available pills available pills level of INF-γ,
IL-1β and
IL-12/Human
trials
Dunaliella salina Diet supplementation 369, and 922.5 mg/ Mice NK and
of commercially kg Macrophage
available spray- activation/
dried preparations In-vivo mice
model
Euglena gracilis β-Glucans 150 µg/mL Activation of
NK cells and
improvement+
in
inflammatory
mediator/
Human PBMC
(Continued)
Table 3.2 Immunomodulatory chemicals are synthesized or have

immunomodulatory effects in marine microalgae. PBMC stands for human
peripheral blood mononuclear cells, NA stands for not available, and w/v
stands for weight/volume. (Continued)
Mechanism/
organism
Extract/fraction/ Active and target cells
Microalgae compound concentration (or model)
Gyrodinium Sulfated 0.1–10 µg/mL Macrophage
impudicum exopolysaccharides activation/
Murine
Skeletonema Total Extract/ NA Activation of
costatum Fractions IL-6/Human
PBMC
We have summarized the algae which have shown immunostimulatory

activity. Pure compounds from microalgae with immunomodulatory
activity will be discussed in the next section.
3.4 Microalgae Anticancer Activity

The significant medical and pharmacological qualities of microalgae have
gotten a lot of attention around the world. Furthermore, several studies
have been conducted on the usefulness of microalgae metabolites in the
treatment of various human diseases, with the growing of algae-derived
compounds gaining much interest in the pharmaceutical industry [32].
Recently, the anticancer properties of some algae-derived resources have
been found to modulate several cellular mechanisms such as cellular cyto-
toxication, downregulate invasion of tumor cells, and enhancement of
cancer cells apoptosis [33, 34]. Many cellular and molecular investigations
have suggested the potent natural antimalignant activity of algae-derived
compounds [35, 36]. Another example is fucoxanthin, a carotenoid found
in microalgae, diatoms, and brown seaweeds that has shown significant
anticancer effects through malignant cell growth inhibition and the pro-
motion of potent anticancer properties via growth by preventing malignant
cell growth, stimulating cancer suppressor genes, and arresting cell cycles,
without affecting tumor cell apoptosis [37, 38]. Data on algae-derived
anticancer resources might help researchers learn more about a new effec-
tive tumor therapy for humans.
Bioactive substances having hypotensive, hypoglycemic, and hypolip-
idemic properties have been derived from microalgae and marine micro
organisms. Bioactive compounds also lower blood pressure.
Because of its high incidence and link to increased morbidity and death,
hypertension is a global health issue. It is the most significant risk factor
for cardiovascular disease, outnumbering cigarette smoking, dyslipidemia,
and diabetes [39], and is thought to be responsible for 54% of all strokes
and 47% of all heart attacks, and is a main cause of ischemic heart disease
worldwide [40]. There have been reports of peptides with antihyperten-
sive action [41]. Peptides from several species of microalgae, including
Chlorella vulgaris, Chlorella ellipsoidea, and Spirulina platensis (Arthrospira
platensis) have demonstrated antihypertensive activity.
Many research studies have shown that consuming Chlorella lowers
blood pressure [42]. A hendecapeptide (Val-Glu-Cys-Tyr-Gly-Pro-Asn-
Arg-Pro-Gln-Phe) with angiotensin I-converting enzyme (ACE) inhibi-
tory action was identified from the pepsin hydrolysate of proteins from
C. vulgaris [43]. The isolated hendecapeptide’s inhibitory kinetics demon-
strated a noncompetitive binding mechanism, indicating that it has a sig-
nificant level of ACE inhibitory action. ACE is a hypertension-converting
enzyme that accelerates the conversion of angiotensin I to the powerful
vasoconstrictor angiotensin II [44] and inactivates the vasodilator brady-
kinin The biochemical features of this isolated hendecapeptide, together
with the low cost of microalgae protein, make it an appealing option for
developing a high-value product for BP management [43]. The alcalase-
proteolytic hydrolysate of C. ellipsoidea protein likewise had substantial
ACE-inhibitory activity and was fractionated into three molecular weight
ranges, with the Fr range being the most active fraction of less than 5 kDa
showing the highest ACE-inhibitory activity.
The peptide Val-Glu-Gly-Tyr (467.2 Da) was found to be an effective
ACE inhibitor. The isolated peptide has ACE-I inhibitory properties and
was a competitive inhibitor of ACE. In spontaneously hypertensive rats,
oral treatment of the isolated peptide can considerably lower systolic blood
pressure. Oral administration of C. vulgaris peptidic fractions into spon-
taneously hypertensive rats resulted in significant antihypertensive effects.
The peptides (Ile-Val-Val-Glu, Val-Val-Pro-Pro-Ala, Ala-Phe-Leu, Ala-
Glu-Leu, and Phe-Ala-Leu) extracted from C. vulgaris pepsin hydrolysates
were shown to inhibit ACE-I [64]. Chlorella is thought to reduce blood
pressure via modulating the rennin–angiotensin system. Furthermore,
S. platensis hydrolysate and purified peptide fractions Ile-Ala-Pro-Gly,
Ile-Ala-Glu, and Val-Ala-Phe have been demonstrated to have ACE-I

inhibitory effects [45, 46]. The high amount of branched and aromatic
amino acids in marine proteins, such as Ile, Val, Phe, and Tyr, has been
reported to be responsible for the ACE-I inhibitory activity. Moreover,
branched amino acid residues at N-terminal positions and aromatic amino
acid residues at C-terminal positions in the substrates or competitive
inhibitors could also be preferred for anti-ACE activity [46].
3.5 Potential of Microalgae in Quality Enhancement

of Natural Products
Natural products are defined as products with natural origins, such as
animals, plants, or microbes, that have not undergone any processing or
treatment other than a simple preservation method [47]. It is possible to
incorporate high-value bioactive chemicals derived from microalgae bio-
mass into the vast majority of consumer products on a regular basis to
increase their nutritional and functional value.
3.5.1 Pharmaceutical Industry

Microalgae have drawn a great deal of interest in the pharmaceutical indus-
try in recent years for their potential therapeutic applications. Various
research investigations have shown that bioactive chemicals derived from
microalgae biomass have therapeutic qualities such as antibacterial, antivi-
ral, antifungal, antitumor, and neuroprotective effects [48, 49]. Anticancer
medicines, particularly those that are poorly water-soluble, are delivered
in a targeted manner. Diatomaceous earth microparticles, which are
derived from marine microalgae, are utilized in cancer targeted therapy,
such as colorectal cancer. The compounds were coated with vitamin B12,
a tumor-targeting drug, before being loaded with cisplatnum or cisplatin,
an anticancer agent, for delivery of the cancer drug to the targeted site to
kill cancer cells [50].
3.5.2 Cosmetics and Personal Care

Microalgae produce substances that have an endless number of possible
skin advantages, such as improving blood circulation, moisturizing the
skin, triggering cell renewal and metabolism, strengthening skin resis-
tance, and having an anti-inflammatory effect. Oral care, skin care, sun
care, hair care, decorative cosmetics, body care and perfumes are among
the personal care products. Skin care products range from facial cleanser,
toner, scrub, essential oil, moisturizer, and masks to restore, protect, and
regenerate the skin with various functions such as hydration, brightening,
pore-tightening, and anti-aging.
Skin care products made from microalgae biomass are a topic of dis-
cussion. For over 30 years, the Daniel Jouvance company has formulated
all of its products with microalgae as part of their Algo [2] product line,
including face care, body care and personal care. For example, Daniel
Jouvance’s ALGO[2]IODE has a high concentration of marine iodine from
Thalassiosira to help postpone the creation of new adipose cells, result-
ing in a 7-day slimming cure; while. Dunaliella salina microalgae, which is
high in marine glycerin, has been used in the their AQUACEANE line as
a potent moisturizing ingredient that keeps skin hydrated for a long time.
ÉCLACÉANE from Noctiluca microalgae, which releases visible and shim-
mering light on the ocean’s surface, provides a fresh source of radiance to
the skin (Table 3.3).
Furthermore, certain cosmetics made from microalgae have been
commercialized. PEPHA®-TIGHT, for example, is a patented pure, one-
of-a-kind natural skin firming and highly purified biotechnologically
manufactured extract from N. oculate microalgae to be used in anti-aging
creams [51].
3.5.3 Food Industry

The Food and Drug Administration (FDA) in the United States considers
algae-based goods or additives to be safe [52]. Microalgae-based culinary
ingredients include cookies, biscuits, pasta, and dairy products, to name
a few [53]. Bioactive substances from microalgae can be added to dairy
products for health advantages. For example, Arthrospira sp. in flora can
help probiotics thrive in fermented milk and yogurts by promoting their
development and viability [54]. Apart from yogurt, Chlorella sp. has also
been used in cheese to increase hardness and springiness while lower-
ing meltability and cohesiveness [55]. Arthrospira platensis phycocyanin
extracts have been introduced in the baking of cookies to increase fiber
and protein content [56]. The addition of H. pluvialis to cookies helps to
lower the glycemic response while also increasing antioxidant capacity
[57], and the protein and antioxidant content of cookies is increased by
integrating C. vulgaris, T. suecica, A. platensis, and P. tricornutum. Pigments
and carotenoids from microalgae can be used as food additives as color-
ings and thickeners [58]. Dunaliella sp., Chlamydomonas sp., Chlorella sp.,
Table 3.3 Properties of microalgae for application in skin care products.

Microalgae Function
Monodus sp., Thalassiosira sp., Integrated into anti-aging products
Chaetoceros sp., and Chlorococcum for collagen stimulation
Phaeodactylum tricornutum Improves skin elasticity and
firmness as well as protects skin
against UV exposure
Chlamydocapsa sp. (snow algae) Hydrates skin following exposure
to dry climates, UV radiation or
the cold
Spirulina platensis Protects against free radicals’
harmful activity in the dermis
and epidermis
Chlorella vulgaris and Spirulina maxima Produce vitamins that help to get
rid of dark circles, refresh and
purify the skin
Aurantiochytrium sp., Thraustochytrium Produce squalene that is used
sp., and Schizochytrium sp. in moisturizing lotions to
provide ideal skin properties
by stimulating emollient and
antistatic actions
Cyanidioschyzon sp., Synechocystis sp., and S. platensis generate carotenoids

that are used as a food colorant. Arthrospira sp. has also been employed as
an enrichment element in extruded snack foods [59]. Microalgae such as
Spirulina platensis can be employed as a protein element in drinks, such
as sports nutrition beverages, as S. platensis proteins contain all the amino
acids needed to increase the athletes’ endurance and performance [60].
Microalgae can also be incorporated into pasta, which is a prominent
food in the diets of Europeans and Asians. It has no effect on pasta cooking
or texture [61], and a high microalgae concentration in pasta improves
stickiness and maintains elasticity. C. vulgaris and A. maxima can be put
into fresh spaghetti to boost the nutritious content [61]. Pasta made with
D. vlkianum and I. galbana contains -3 PUFAs and antioxidants that may
have health benefits [62]. Another fascinating feature of microalgae like I.
galbana, P. tricornutum, C. calcitrans, M. subterraneus, S. obliquus, N. gadi-
tana, C. cohnii, and T. pseudonana is their ability to synthesize lipids (fatty
acids) in the food industry [63].
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4
Application of Astaxanthin and
Carotenoids Derived from Algae for
the Production of Nutraceuticals,
Pharmaceuticals, Additives,
Food Supplement and Feed
Abiola Folakemi Olaniran1*, Joshua Opeyemi Folorunsho1,
Bolanle Adenike Akinsanola1, Abiola Ezekiel Taiwo2, Yetunde Mary Iranloye1,
Clinton Emeka Okonkwo3 and Omorefosa Osarenkhoe Osemwegie1
1
Landmark University SDG 12 (Responsible Consumption and Production Group),
Department of Food Science and Microbiology, Landmark University, Omu-Aran,
Kwara State, Nigeria
2
Faculty of Engineering, Mangosuthu University of Technology,
Durban, South Africa
3
Department of Food Science and Technology, College of Agriculture and Veterinary
Medicine, United Arab Emirates University (UAEU), AI Ain, United Arab Emirates
Abstract
The importance of astaxanthin and carotenoids for the production of nutraceu-
ticals, pharmaceuticals, additives, food supplement and feed cannot be overem-
phasized due to several health benefit among which are anti-inflammatory and
immune booster properties in people and animals. They are a major natural source
of pigments and are high in antioxidants that have been documented to be more
competent compared with vitamins C, E, carotene, lutein, lycopene, zeaxanthin,
etc. Therefore, it’s vital to explore the use of astaxanthin and carotenoids from
algae; hence, this chapter discusses the potentials of optimizing astaxanthin and
carotenoids from macro- and microalga cells. Utilization of astaxanthin and carot-
enoids from algae must be extended beyond serving as a food colorant by lever-
aging its powerful antioxidant potentials as a scavenger using microencapsulation
*Corresponding author: [email protected]; [email protected]
95
to reduce oxidation damage which is germane in treatment of several documented

health challenges. Hence, considering the future prospects of maximizing astax-
anthin and carotenoids produced from algae as a major raw material in manufac-
turing of nutraceuticals, pharmaceutical products, and nutritional supplements on
an industrial scale for the global market is a progressive phase towards attaining
sustainable technology and agriculture that is eco-friendly and supports healthy
living of humans and animals.
Keywords: Algae, bioactive compounds, carotenoids, astaxanthin, food
supplement, health, sustainable consumption, nutraceuticals
4.1 Carotenoids and Its Characteristics

Carotenoids are naturally occurring chemicals. Photosynthetic organisms,
as well as certain fungi and bacteria, biosynthesize them. Carotenoids
(CTN) cannot be biosynthesized by the great majority of animals, but
they may be absorbed into the diet and structurally changed afterwards.
Certain invertebrate species, like hemipteran and dipteran insects and
mites, have been shown to manufacture carotenoid [1]. Carotenoids
are a cluster of over 1000 pigments that occur naturally and synthe-
sized by several organisms like plants, photosynthetic bacteria, fishes
and microalgae [2]. They range from red to orange to yellow pigments
that give the characteristic color to tomatoes, canaries, carrots, pump-
kins, flamingos, shrimps, salmon, lobsters, among others. They serve
two key roles in algae and plants: they provide, via non-photochemical
quenching, photoprotection, and they absorb light energy in photosyn-
thesis [3, 4]. Based on the presence of oxygen, CTN are categorized into
Xanthophylls (contains oxygen) and Carotenes (pure hydrocarbons with
no oxygen). CTNs are formed from isoprene that consists of 40 carbon
atoms, making them derivates of tetraterpenes. They are the dominant
color pigments in leaf coloration during the autumn season for about
25% plant species. Their structure allows for different biological activi-
ties, including plant coloration, cell communication, photosynthesis and
photoprotection. The length of CTN compound plays a part in plants
pigmentation, and the span of polyene tails shows which wavelength of
sunrays the plant absorbs. They are lipophilic in nature as a result of the
presence of aliphatic chains that are unsaturated, which can be seen in
some fatty acids. Depending on the presence of bile salts and fats, these
fat-soluble compounds are adsorbed in human beings [4].
Astaxanthin and Carotenoids Derived from Algae 97
4.1.1 Sources of Carotenoids

Carotenoids are regarded as one of the most common and widely distrib-
uted naturally occurring lipid-dissolvable pigments, despite having little
natural presence. They are found in fruits, flowers, leaves and seeds. In ter-
restrial animals, they’re primarily localized in fatty tissues like abdominal
fat and egg yolk [5]. Bacteria and algae, which can manufacture a broad
range of carotenoid structures, have a particularly vast diversity. Natural
sources of carotenoids include plants, microalgae, bacteria, and fungus.
Carotenoids are produced by a variety of bacteria and accumulate in
the chromatophores, which are connected to the membrane (cytoplasmic
membrane). Carotenoids, when in the form of beta-carotene, are found
almost exclusively in Halobacterium spp., resulting in a brilliant red cell
suspension orange-pigmented, Gram-negative, rod-shaped, aerobic motile
by peritrichous flagella, and astaxanthin-enriched Paracoccus carotinifa-
ciens isolated from soil [6]. This organism produces carotenoids, primarily
astaxanthin, but not bacteriochlorophyll. Q-10 is the ubiquinone system.
Several fungal families, in comparison to other species, are able to generate
and store exceptionally large amounts of carotenoids intracellularly, a trait
shared by some microalgae. Several fungal phyla, including Ascomycetes,
related species, Basidiomycetes, and also the Deuteromycetes, generate sig-
nificant quantities of carotenoids in contrast to other organisms such as
algae, bacteria, plants, and mammals [7].
Microalgae, to the contrary, proffer a quality source of carotenoid col-
ors, polyphenols, vitamins, fats, and proteins. Algae are basic unicellular
creatures (microalgae) that can be found alone or in colonies, and they
can also be found in very sophisticated pluricellular tissues (macroalgae)
[8]. Microalgae cultivation has certain distinct benefits over traditional
plant-required sources, including a quicker cultivation time, processing
time, and harvesting cycle, and also the possibility to be cultivated on
waste products. Despite the advantages noted, cost-effective and large-
scale synthesis of carotenoids cultivated from algae is still extremely diffi-
cult during production, development and downstream extraction [9]. As
a result, an integrated/merged bioprocessing strategy employing microal-
gae must address both upstream microalgae production and downstream
carotenoids harvesting and extraction. The presence of stiff cell walls in
many algae species creates challenges since it inhibits full recovery of bio-
active chemicals [8, 10].
Carotenoids are responsible for the wide-ranging colors in leaves and
flowers, as well as providing a diversity of smells in plants. Carotenoids
are completely expressed in many flowers because they are usually found
aggregated in chromoplasts, which are usually in the absence of chloro-

phyll pigment [11]. Carotenoids found in terrestrial plants are mostly
yellow and red xanthophylls like capsanthin, the popular lutein, violax-
anthin, zeaxanthin, or neoxanthin, which are all part of the usual xantho-
phyll cycle and are regularly involved in photosynthetic protection [12].
Several variables including genotype, maturation period, growth method
with weather conditions, and also processing, influences the composition
and kinds of prospective carotenoids in the respective plants. Different
classes and quantities of carotenoids can be found in different sections of
the same plant. Fruit peel, for example, is usually higher in carotenoids
than fruit pulp [13]. Carotenoids are divided into two sets based on their
structures: hydrocarbon carotenoids and xanthophylls. Carotenoids with
polar properties are known as carotenes and include alpha-carotene,
gamma-carotene, beta-carotene, phytofluene, lycopene and phytoene [14].
Xanthophylls are known to be more polar than chlorophylls and include
oxygen at the carboxy-, hydroxy-, keto-, methoxy-, and epoxy- positions.
Zeaxanthin, lutein, astaxanthin, and fucoxanthin are examples of xantho-
phylls. Carotenoids are also categorized by the presence and absence of
ring groups at the chain’s ends [3, 16].
Xanthophylls are yellow pigmentations found to occur in nature that
include oxygen atoms. Lutein is a dihydroxy-carotene composed of
carotenoids with a hydroaromatic structure and an alcohol group. It has
hydroxyl groups on both of its beta-ionone rings. It is a pigment that gives
chicken fats, and their products, including feathers and egg yolk, their
color [10]. The yellow-pigmented lutein reported in plants is said to be
an organic colorant that may be found on the leaves of green crops like
spinach and black pepper. It’s most commonly seen in fatty acid covalent
connections. Lutein and zeaxanthin have identical chemical formulae; in
other words, they can be said to be isomers, but are not referred to as ste-
reoisomers. The situation of the two-fold bond within the terminal ring
differs between the two. A popular prevalent carotenoid alcohol discovered
in nature is zeaxanthin. It’s a pigment that gives maize and several plants
their color. Picrocrocin, which gives saffron its flavor and scent, is formed
when zeaxanthin breaks down. The alcohol group in the beta-cryptoxan-
thin carotenoid has a hydro-aromatic structure with an OH group in the
first ring. The second ring is the beta-ionone, which may be used to make
one molecule of vitamin A. Beta-cryptoxanthin is a naturally occurring
carotenoid pigment usually found in vegetables and fruits like mandarin,
bell pepper, and sweet potato, which offers various health advantages [16].
Beta-cryptoxanthin and beta-carotene are related. Beta-cryptoxanthin
was given only one OH group. Although beta-carotene may be found in
great amounts in a diverse fruits and vegetables, beta-cryptoxanthin is only

found in a few dietary sources but in high concentrations.
Carotenes are carotenoids with hydroaromatic rings. These rings can be
found at both ends of the four isoprene molecules,. Each carotene molecule
has two hydroaromatic rings as a result. These hydrocarbons have three
ionone rings which are known as ionospheric rings. There are two types of
ionone rings: alpha- and beta-ionone rings [15]. Alpha- with beta-ionone
rings have one double bond and are closed rings. In beta-ionone rings and
pseudo rings, the location of the double bond is not the same. Two double
bonds make up the pseudo-ionone ring. Carotene is an eight-isoprene-unit
biochemically produced terpene. Carotenoids are vitamin A precursors
that are metabolized to vitamin A in the human body. One molecule of
vitamin A is generated from alpha-carotene and gamma-carotene, whereas
two molecules of vitamin A are created from beta-carotene. Between them,
there are four molecules of polymerized isoprene. Vitamin A is made up of
half of an alpha-carotene molecule. A beta-ionone ring and two isoprene
molecules are linked to one end of vitamin A. Carrots, squash, tomatoes,
bell peppers, and dark green-colored vegetables are high in alpha-carotene,
the second most prevalent type of carotene [17]. The provitamin beta-car-
otene is fat-soluble. Vitamin A is the active form. The beta-ionone ring is
present on both ends of beta, which distinguishes it from alpha. Vitamin A
is created when beta-carotene is split into two molecules. It may be found
in cereals, also in fruits, vegetables and oils. One molecule of vitamin A is
generated when the molecule is divided, with ending the beta-ionone ring
and pseudo-ionone ring at the other side. Lycopene is a carotenoid with an
olefinic structure [18]. Vegetables, watermelons, grapefruit, and rosehip
are all high in lycopene. Because lycopene dissolves in oil, it is absorbed
more readily by the digestive system when oils are present. Phytoene, a
40-carbon and 3-conjugated double-bond molecule with a symmetric
structure, acts as an intermediary in the synthesis of phytoene carotenoids.
Phytofluene is a carotenoid pigmentation found in tomatoes and other
plants that are orange in hue [19].
4.1.2 Production/Extraction of Carotenoids

Recovery of important chemicals from several natural origins follows ana-
lytical chemistry principles, and is widely known to be done in five stages:
(i) macroscopic preprocessing, (ii) macro- and micromolecules differenti-
ation, (iii) segmentation, (iv) purification, and lastly, (v) product creation.
This approach was created to optimize the output of the specific targeted
mixtures, meet the manufacturing step-by-step processing needs, separate
the valuable substances from any hazardous compounds and impurities

found, minimize functionality loss during the processing stage, and assure
the end product’s food grade nature. Macroscopic pretreatment, in par-
ticular, attempts to modify the water, solids, and lipids content, activate
or deactivate enzymes, moderate the microbial burden, and ultimately
enhance matrix permeability [20]. A wet milling phase is required when
the substrate is a vegetable or fruit byproduct so as to expedite and raise
the output of the subsequent extraction stages. This is accomplished by
inducing swellings and softness of tissue, which allows for greater extract-
ant integration within the food matrix. If the substrate is wastewater, on
the other hand, concentration is used with the goal of eliminating water
and raising the content of useful components [21]. Alcohol precipitation
is the most common technique for separating smaller chemicals, either
acids or ions, from macromolecules, such as nutritional fibers, pectin and
hydrocolloids in the second recovery step, which are accumulated in the
insoluble alcohol residue. The subsequent phase in downstream processing
is of utmost importance, and must be standardized to details, with many
techniques applied to the target molecules and physical properties (i.e.,
solubility or its volatile nature). Contingent on the form of the original
substrate and the specific compounds, many traditional and new methods
have been utilized for this goal. The most common and extensively utilized
approach is solvent extraction. This occurs because it is highly convenient,
as the solvent acts as a physical carrier for transferring important chemi-
cals across multiple physical phases while maintaining their physicochem-
ical properties (e.g., volatile nature or solubility) [22].
Carotenoids must be extracted from fruits and vegetables in a simple,
quick, and low-cost manner for commercial use. The employment of tra-
ditional extraction methods, on the other hand, has its drawbacks. Not
only did these tactics endanger human health and also the environment,
they also jeopardized the extraction process. Long extraction times and an
enormous volume of solvent were also required. Furthermore, traditional
technologies have a number of flaws that limit their application in actu-
ality. Membrane technologies (such as ultrafiltration) need more energy,
whilst others have a high operating cost [23, 24].
The drawbacks of traditional techniques might be addressed by employ-
ing new (usually non-thermal) technologies, dubbed emergent technol-
ogies. Shortening process time and residence times to enhance the heat
as well as mass transfer, improve the superiority of product, control the
reactions (Milliard), enhance functionality (which also protects from envi-
ronmental stresses), and elongate preservation are all benefits of these tech-
nologies that are currently being researched and, in many instances, used
in industries involved with food. Radio-frequency drying, cold plasma

treatment, ultrasound-assisted extraction (UAE), electro-osmotic dewa-
tering, high-voltage electrical releases, homogenization, pulsed electric
field, and nanoencapsulation are the most current evolving technologies
being experimented on in the comprehensive field of food science. High
hydrostatic pressure, for example, enhances the mass exchange rate of
carotenoids during extraction by aiding plant cell penetrability and allows
molecules to diffuse. MAE works by utilizing microwaves to increase pres-
sure on the cell wall caused by moisture evaporation within the cells [22].
Microwave energy permeates the biomaterials, then they interact with
molecules that are polar, such as water, to generate heat. A rise in pressure
causes the physical characteristics of the sample tissues to be disrupted,
and the rise in permeability of the matrix lets the extraction solvent pen-
etrate more deeply, improving carotenoids recovery. The microwave’s
impact is determined by the ionic solvent’s dielectric susceptibility and the
solid plant matrix. Because H2O has a relatively high dielectric constant,
moistening all plant samples with it can enhance recovery of carotenoid
[22]. The rehydrated biomaterial can also interact more effectively with
the energy of a microwave to generate heat, swell within the cytoplasm,
and finally rupture, releasing carotenoids into the solvent. It’s important to
choose the right ionic solvent for the job. Solubility, dissipation, and dielec-
tric constant variables are three important aspects to consider when choos-
ing a solvent. In comparison to non-polar solvents like hexane, which has
a relatively low dielectric constant, high dielectric constant solvents like
water, ethanol, and methanol can absorb microwave radiation significantly
[25]. The relationship between the solvent and the microwave may be
modulated using solvent mixes. The efficiency of a microwave-heated liq-
uid is represented by the dissipation factor. Despite its excessive dielectric
constant, water possesses a poor dissipation factor, making it ineffective
in heating up the moisture within the sample. As a result, even without
using water as the ionic solvent, microwave can aid in the extraction of
carotenoids [21].
As a pretreatment, enzymatic treatment is generally executed preced-
ing traditional solvent extraction; hydrolytic enzymes such as cellulase and
pectinase are generally used by enzyme-assisted extraction in plant. They
disrupt the cell wall’s structure to enable effective extraction and release of
bioactive substances. When compared to commercial enzymes, enzymes
have been found to produce a carotene that is high in carotene concen-
tration with a shorter processing time. The breakdown of the structure of
the cell wall generally speeds up metabolic transformations, which results
in unappealing colors and flavors. These variations, in contrast, were not
obvious in the plant matrices treated using enzymes. Because the extract-
ants formed by cellulase and pectinase, such as carotenoids, are fastened to
proteins, the pigment structure that is highly unsaturated remains stable.
The enzyme concentrations used for plant pretreatment vary from 0.01%
to 0.1% (w/w). The presence of water is required for enzymatic hydrolysis
to occur. Excessive water, on the other hand, causes the development of an
aqueous phase that inhibits the solvent from interaction with carotenoids
and hence inhibits the extraction time process. Agitation is crucial in enzy-
matic treatment because it allows enzyme to diffuse from the aqueous into
the solid stage, which improves cell wall lysis and increases extraction yield
[21, 26].
4.2 Astaxanthin and Its Characteristics

Astaxanthin (AXT) is a red pigment belonging to the Xanthophyll fam-
ily, which are oxygenated carotenoids derivatives from lycopene basically
in plants. Although it is classified as a Xanthophyll, it is currently used
to describe compounds of carotenoid composed of oxygen-containing
components [27]. AXT is also one of the main pigments and secondary
metabolites synthesized naturally by a number of yeasts, bacteria, and
microalgae. It is also commonly found in salmon (Pacific) fish and gives it
the characteristic pink color. With the chemical formula C40H54O4, molec-
ular mass 596.841 g/mol; the red to orange color of AXT is due to the
elongated conjugated chain (which are interchanging single and double) at
the center of the compound. The antioxidant properties of ATX and other
carotenoids are linked to its double-bond conjugated chains which result
in a section of decentralized electrons which are released to minimize oxi-
dizing reacting molecule [28].
Algae, salmon, yeast, shrimp, and crayfish are all natural sources of
astaxanthin. The majority of commercial astaxanthin comes from Phaffia
yeast, Haematococcus spp., and chemical production. One of the greatest
sources of astaxanthin that occur naturally is Haematococcus pluvialis. The
greatest astaxanthin level in the raw Oncorhynchus class was investigated
to be in the range of 25–39 mg/kg meat in salmon; however, low source of
astaxanthin content was recorded in chum salmon. The concentration of
astaxanthin in farmed Atlantic salmon meat was reported to be 5–9 mg/
kg flesh. Microorganisms with the highest percentage of astaxanthin per
dry weight include: Haematococcus pluvialis (about 3.5%), Chlorococcum
(0.2%) and Neochloris wimmeri (0.6%). Xanthophyllomyces dendrorhous,
a Phaffia yeast, produces 100 percent non-esterified astaxanthin, which is
beneficial since it can be easily absorbed and does not need to be hydro-
lyzed in the fish’s system. Unlike bacteria-derived and synthetic astax-
anthin, the yeast-derived astaxanthin is mostly comprised of the (3R,
3’R)-form, which is a common astaxanthin source in nature [29].
4.2.1 Production/Extraction of Astaxanthin

Astaxanthin is a lipophilic molecule that dissolves in a variety of solvents
and oils. Astaxanthin is extracted using edible oils, solvents, acids, and enzy-
matic techniques. Astaxanthin accumulates in Haematococcus encysted
cells. The pigment Astaxanthin was recovered from Haematococcus using
various treatments using acids, with HCL recovering up to 75% of the pig-
ment [12]. When cystic cells were introduced to acetone (40% acetone) for
2 min at 80 °C, then cellulose, kitalase, and acetone powder, about 70% of
the astaxanthin was recovered. The use of sonication to treat hydrochloric
acid at different temperatures for between 15 and 30 min yielded a high
astaxanthin output. In another investigation, astaxanthin was extracted
from Haematococcus using vegetable oils (maize, olive, soybean and grape
seed). The astaxanthin in the cell was retrieved from the oils when the cul-
ture was combined with oils, with olive oil yielding the greatest recovery
of 93%. Under acidic conditions, Astaxanthin (about 1.3 mg/g) was recov-
ered from the yeast Phaffia rhodozyma [30]. Microwave-aided extraction
at around 75 °C for about 5 min yielded 75% of astaxanthin; nevertheless,
the astaxanthin concentration in acetone extract was high. When intro-
ducing supercritical fluid extraction using ethanol and sunflower plant oil
as co-solvent, the yield of astaxanthin from Haematococcus was 80–90%.
Astaxanthin was isolated many times using different solvents, then col-
lected and vaporized using a rotary evaporator. The extract was then dis-
solved again into a solvent, and the absorbance of the extract was measured
between 475–480 nm to determine the astaxanthin concentration. The
extract may also be tested for astaxanthin quantity and identification using
high-pressure liquid chromatography (HPLC) and mass spectra (MS) [16].
Currently, most astaxanthin production takes place outside of the trop-
ics, owing to the excessive lumination strengths and temperatures neces-
sary for astaxanthin production in the red stage, that would be unprofitable
inside; nevertheless, most of its production takes place outside of the trop-
ics [6]. Because of the high light expenditures, the red stage might account
for about 60% of the power expenses in indoor production. Only Fuji
Chemicals use an all-indoor manufacturing method. In its BioDome™
system, Fuji Chemicals abandoned H. pluvialis cultivation outside. Due
to unfavorable conditions for astaxanthin synthesis in outdoors temperate
zones, commercial manufacture of astaxanthin derived from H. pluvi-

alis is limited, and only in-house culture is possible. Aragreen, based in
Gloucestershire, was looking at producing astaxanthin from H. pluvialis,
however, the firm went bankrupt in 2017. There are a variety of industrial
cultivation methods, with the majority seeking to use a more sustainable
manufacturing approach. In the instance of Cyanotech, H. pluvialis is cul-
tivated inside in the production stage under carefully standardized and
supervised growth conditions before being moved to open ponds in the red
stage for astaxanthin induction [30]. AlgaTechnologies uses photovoltaic
cells and performs their entire process outside in photobioreactors (PBRs)
to make use of natural sunshine. Algalif, on the other hand, uses light-
emitting diodes to harness geothermal energy for a complete industrial
process indoors (LEDs). The majority of firms are focusing on phototro-
phic culture, while Fuji Chemicals, for example, is looking into mixotrop-
hic cultivation. The encasement process culminates in the production of
spores during astaxanthin production, which can take between around
3–5 days (cysts). The aplanospores are collected with the help of gravity
and further concentrated using ultracentrifugation after culture and astax-
anthin induction. The biomass is subsequently dried using spray-drying,
which is more cost-effective than freeze-drying or drum-drying [31]. An
extraction method is used to break down the cell walls of dried thick-
walled aplanospores and make all astaxanthin accessible. Because the walls
of the aplanospores are resistant to digestion by animals (in feed supple-
ment application) and humans (in nutraceutical applications), they must be
disturbed in order for astaxanthin to become accessible. In the extraction
process, care must be taken to prevent oxygen exposure and increased tem-
peratures, both of which can degrade astaxanthin and can result in process
losses. On a commercial basis, supercritical fluid extraction (SFE) using
CO2 (ScCO2) is the most popular method for extracting astaxanthin. The
dried end-product is generally treated with an effective preservative before
being delivered to feed producers to be included in designed feed [6].
4.2.2 Historical Perspective of Consumption of Alga as Food

and Utilization in the Food Industry
Algae have been utilized as food for humans since ancient times. For
instance, in the Eastern part of the world and the Pacific region of Asia, eat-
ing algae has long been an accepted custom. However, in Western nations,
the attention garnered by food products from algae has only greatly
expanded in recent years, to the degree that diverse palatable species of
algae are presently usually advertised for use in the European Community
and the American continent [32]. Acceptance of algae has additionally

expanded as of late, particularly among veggie lovers, because of their uti-
lization in connoisseur cooking as extra dishes, toppings, and ingredients
on café set menu these days. Algae suggest intriguing possibilities for the
creation of inventive foods or to potentially foster novel products in order
to mitigate the shifting perceptions of consumers, opening doors to new
food products in the food industry, which requires ceaseless novelty [33].
Moreover, there will probably be a surge in the utilization of algae related
to the requirement for extra food sources as the population keeps on devel-
oping. Algae has been found to be utilized as a supplement in feed for
animals and as part of manures. The nourishing properties of algae are a
significant wellspring of supplements like vital nutrients and minerals, nour-
ishing fiber, crucial unsaturated fats and good proteins [34]. Constituents
from marine algae like hydrocolloids (carrageen, alginate and agar) likewise
afford mechanical benefits in industrial food processes whenever utilized as
emulsification, gelling and thickening agents during food and drink manu-
facturing. As of late, attention to marine algae has been on the rise because
it is seen as the origin of bioactive elements having numerous uses in the
improvement and creation of functional food sources [35].
The developing understanding of the connection between food and well-
being is prompting new bits of knowledge about the impact of food elements
on physical capacity and wellbeing. The logical result of this is the public’s
interest for solid, nutritious food sources with extra health-advancing capac-
ities, like functional food sources [36]. Algae can be incorporated into prod-
ucts as algal extracts of selected elements or, alternatively, pieces of dried
algae can be crushed and utilized in the manufacture of food and drinks. In
addition to being utilized as single-cell proteins, lately, microalgae are like-
wise projected as plants with living-cells required in creating different valu-
able biochemicals and bioenergies utilized in poultry, production of food,
hydroponics, and drug companies because of the presence of various helpful
compounds. Generally, the pattern towards expanding a healthy interest for
algal items on a worldwide basis originated from a more noteworthy focus
on wellbeing and more extensive utilization of food additives [37].
4.3 Application/Utilization of Astaxanthin

and Carotenoids in Different Sectors
Astaxanthin and carotenoids provide wide benefits in various fields and
are applied in several areas such as pharmacology, food industry and feed
production. Carotenoids have lengthy conjugated double bonds in their

polyene chains, which function as antioxidants by dousing oxygen and
scavenging free radicals to stop any domino effect. Carotenoids’ natu-
ral advantages might be linked to its antioxidant capabilities, which are
ascribed to their physicochemical interactions with different cell mem-
branes. Carotenoids containing an oxo functional group have greater
antioxidant activity without contributing to pro-oxidation. Comparing
astaxanthin to other carotenoids, including lutein, lycopene, beta-carotene,
and alpha-carotene, astaxanthin exhibited greater antioxidant activity [38].
With Haematococcus biomass as a major source of astaxanthin, the anti-
oxidant enzymes like peroxidase, catalase, and thiobarbituric acid reactive
materials were shown to be high in rat liver and blood plasma. In rats,
astaxanthin, followed by beta-carotene, and lutein, provided the highest
protection against free radicals. Astaxanthin has a unique chemical struc-
ture with the presence of hydroxyl and keto moieties on each ionone ring,
which contribute to its strong antioxidant capabilities. Astaxanthin has
ten times the antioxidant capabilities of zeaxanthin, canthaxanthin, lutein,
and beta-carotene, and a hundred times more antioxidant activity than
alpha-tocopherol. Astaxanthin’s polyene chain ends trap free radicals in the
cell membrane, while its terminal ring also scavenges free radicals on the
cell membrane’s inner and outer surfaces. Antioxidant enzymatic under-
takings were measured in rabbit serum after astaxanthin was added to their
diet, and superoxide dismutase and also the enzyme thioredoxin reductase
activity were increased, while paraoxonase activity was suppressed in the
oxidatively induced rabbits. When astaxanthin was administered to etha-
nol-induced gastric ulcer rats, the levels of antioxidant enzymes rose. This
proves the effects of astaxanthin as an oxidant and its application in anti-
oxidant pharmaceutical drugs [24].
Astaxanthin can also be used as an anti-inflammatory drug for hyper-
tension, type 2 diabetes, hypercholesterolemia, and obesity, which are
among the chronic conditions exacerbated by inflammation. It has a strong
anti-inflammatory impact that may be linked to its antioxidant properties
and leads to different physiological formations that improve cardiovascu-
lar function. Atherosclerosis is a degenerative, chronic illness that affects
large- and medium-caliber supply arteries. Atherogenesis, the first stage of
the process, is marked by the accumulation and formation of low-density
lipoprotein (LDL) inside the vascular wall subendothelial layer, which is
sensitive to irritation interceded by natural and varied resistance responses
[18]. Astaxanthin’s anti-inflammatory properties have been demonstrated
in the prevention of atherosclerosis. The main damage associated with
single-molecule patterns recognized by macrophages are those generated
by oxidation of LDL, which are liable for the initiation of the inflamma-
tory flow involving the discharge of cytokines and chemokines, which
acquire more resident vascular macrophages and monocytes from blood.
Not only has astaxanthin been proven to reduce oxidative stress in T cells,
but it has also been demonstrated to modulate their function. In scientific
research on young healthy females, supplementation using astaxanthin
induced mitogen-lymphoproliferation which increased the subpopulation
of T lymphocytes devoid of altering the number of T killer/helper cells.
It also improved the reaction to tuberculin, a marker of T lymphocyte
function. Using an animal model of nonalcoholic steatohepatitis, astaxan-
thin decreased T-helper and T-killer cell migration in the liver, reducing
inflammation and insulin resistance [39–41].
When compared to fish oil alone, 45 days of supplementation with the
fish oil having astaxanthin (with a body mass of 1 mg/kg) substantially
reduced T-cell proliferation in reaction to mitogens and RONS produc-
tion. Astaxanthin substantially reduced the activation of T lymphocytes
produced by phytohemagglutinin in several in-vitro tests with peripheral
mononuclear cells from individuals with different allergic inflammatory
diseases. As a result, astaxanthin has been demonstrated to have a distinct
modulatory impact on T cells, either enhancing their overall immunolog-
ical response or reducing potentially harmful activation of the immune
system. However, the function of astaxanthin-mediated T lymphocyte reg-
ulation in the development of cardiovascular illnesses and its risks are yet
unknown.
Recent research on potential applications of astaxanthin as antidiabetic
drug has been reported. Although prediabetes may be managed by diet
and other ways to keep blood sugar in check, the inflammation and oxi-
dative stress induced by elevated sugar in the blood pose a risk for cardio-
vascular disease. Hyperglycemia causes oxidative stress, which harms the
body’s tissues and cells. Inflammation is one of several pathogenic pro-
cesses of type-II diabetes, and after administering astaxanthin in type 2
diabetes patients, it was discovered that astaxanthin can lower IL-6 levels
in patients over time. Reversing prediabetes represents a hugely untapped
possibility for preventing diabetes, which lowers the cardiovascular disease
burden [18, 41, 42].
Notwithstanding the evident nutritional worth of carotenoids, the
unequivocal proof of their relevance in promoting health is exceedingly
difficult owing to the complexity of the nutritional intakes and the human
system. However, multiple data from various research (epidemiological
and lab research) indicate that the use of carotenoids as part of a regu-
lar diet may have health advantages [43]. The fast growth of cancer cells
characterizes tumor development. Cancer cells multiply, which encourages

invasion, migration, and adhesion to target tissue. These stages permit the
tumor cell to acquire the phenotypic of a metastatic cell. Cell prolifera-
tion is controlled by signaling pathways like the MAPK (mitogen-activated
protein kinase) and PI3K (phosphatidylinositol 3-kinases) flows, which are
triggered by growth factors and adhesion proteins [40]. Higher levels of
beta-carotene and total carotenoids in the blood have the strongest cor-
relations to a reduced risk of breast cancer. Breast tumors that are estrogen
receptor-negative (ER-) have a stronger link than those that are estro-
gen receptor-positive (ER+). In the case of ER- malignancies, circulating
alpha-carotene also appears to be protective. Because certain carotenoids
have been shown to suppress the development of both ER+ and ER- breast
cancer cells in the lab, it’s conceivable that their effect in human research
is simply overwhelmed by the hormone effects that are dominant in ER+
tumors [38]. In meta-analyses for the AICR/WCRF study, dietary con-
sumption and blood stages of beta-carotene and other carotenoids were
linked to a diminished risk of lung cancer. Current and previous smoking
intensity and duration were factored into the studies. However, because
tobacco smoking lowers blood beta-carotene levels, the link between lower
beta-carotene levels and increased risk may involve some residual tobacco
confounding. High-dose beta-carotene supplements, on the other hand,
are thought to raise the menace of lung cancer among current and past
smokers [11, 38, 40, 44].
4.3.1 Nutraceuticals
The term “nutraceutic” comes from the English words “nutrition” and
“pharmaceutics.” The phrase describes products made for dietary supple-
ments, herbal extracts, specialized diets, and also processed meals includ-
ing cereals, sauces, and drinks that are utilized for more than just the usual
nourishment. Nutraceutical products are regulated as medicines, food
additives, and dietary supplements in the United States. The phrase isn’t
always defined the same way in different nations, although it’s commonly
described as a food-derived product marketed in medical forms that aren’t
normally connected with food [45]. A substance that has physiological
advantages or protects against several chronic illnesses is described as
a nutraceutical product. These products can be used to enhance health,
slow down the aging process, deter chronic illnesses, prolong life, and also
maintains the body’s function and structure [46].
Nutraceuticals are arranged in a variety of ways depending on the user’s
preference. However, dietary fibers, pre- and probiotics, fatty acids that are
polyunsaturated (PUFA), antioxidants, polyphenols, and carotenoids are all

examples of traditional techniques of defining nutraceuticals. Carotenoids
constitute a wide group of lipophilic tetraterpenoids that are made up of
long, thin molecules in a chromophoric system with a high degree of con-
jugation. They are classified as carotenes or xanthophylls (hydrocarbons
containing oxygen) and are produced by condensation of isoprenyl units.
They are one of several common and widespread yellow to orange to red
pigments found in nature. Fruits, vegetables, algae, fungus, and some bac-
teria produce carotenoids as secondary micronutrients. Nature synthesizes
about 100 million tons of carotenoids, according to estimates. Primary
and secondary carotenoids are two types of carotenoids. Primary carot-
enoids, such as beta-carotene, neoxanthin and violaxanthin, are required
by several plants during their photosynthetic processes, while secondary
carotenoids, such as gamma-carotene, beta-cryptoxanthin, zeaxanthin,
antheraxanthin and capsanthin, are found in fruits and flowers. The pur-
ple color of Proteobacteria, the greenish to brown color of Phaeophyceae,
the yellowish color and texture of birds’ feathers, the orange coloration of
carrots; or the autumn foliage of different deciduous trees, the pigmen-
tation in fungi, mosses, algae, bacteria, and different marine animals or
crustacean exoskeletons, night vision of vertebrates, and even the human
skin coloration are all examples of carotenoids’ wide distribution [18, 26].
Moran and Jarvik [43] found that three different species of arthropods:
Myzus persicae (green peach aphids), Tetranychus urticae (two-spotted
spider mites), and Acyrthosiphon pisum (pea aphids), all have the ability
to synthesize carotenoids after horizontal transfer of carotenogenic genes
from fungi. Also, it was hypothesized that these genes may be found in the
genomes of other arthropods, and that the carotenoid biosynthetic gene
could be one of them. Humans, on the other hand, are unable to manu-
facture carotenoids from scratch and must obtain them from their food, as
carotenoids are required for a variety of biological activities. Only approxi-
mately 40 of them are found in a regular human diet, with 20 of them being
located in human blood and tissues. Carotene, lycopene, lutein, and cryp-
toxanthin account for about 90% of the carotenoids present in the human
body and food. Human absorption and digestion of dietary carotenoids
is a complicated process that may vary based on an individual’s genetic
makeup. Although the dynamics of carotenoids inside the human body
remain mostly unknown, human plasma contains significant quantities
of zeaxanthin, lycopene, lutein, beta-cryptoxanthin, beta-carotene, and
alpha-carotene. Although carotenoids are mostly stored in adipose tissues
and the liver, significant per gram concentrations of carotenoids accumu-
late in the adrenal gland, lungs, corpus luteum, and testes. Human plasma
and tissue contain significant amounts of the colorless carotenoids, phy-

toene and phytofluene.
4.3.2 Food Additives, Supplements and Feed Formulation

The most common way that humans utilize astaxanthin is as a dietary sup-
plement, yet, as of 2018, there has been no sufficient data from scientific
studies to indicate that it changes the risk of illness or human health, and
it is still under investigation. In 2018, the EFSA (European Food Safety
Authority) requested scientific evidence on the safety of astaxanthin from
dietary supplement producers. Astaxanthin is mostly utilized as a pigment
in aquaculture and nutritional supplements in the food sector, as well
as in nutraceuticals and medicines [47]. This carotenoid pigment is well
recognized as an aquaculture feed additive responsible for impacting the
pinkish-red color of the meat of salmon, ornamental fish, trout, shrimp,
crayfish and lobsters, bringing about better quality and acceptability by
customers. The aquaculture industry’s continuing expansion has resulted
in a huge need for astaxanthin pigment. Apart from that, astaxanthin has
anti-inflammatory and immune system boosting properties when used as
a human dietary supplement [47].
Because of its large unsaturated molecular structures, astaxanthin is
particularly sensitive to heat, strong light, and oxidative conditions. When
astaxanthin is exposed to a variety of these circumstances during the
preparation and storage of feed, it may lose its nutritional and biologically
beneficial characteristics. Astaxanthin must thus stay stable when added
to various feed compositions in order to achieve maximum effectiveness.
Milling, mixing, extrusion, pelletizing, and drying are all steps in the feed
manufacturing process. It has been hypothesized that milling has no effect
on the stability of astaxanthin [21]. In fact, the ability to disintegrate or
disturb microalgal cells by grinding seems to be the only significant factor
in maximizing intracellular astaxanthin consumption. The machinery uti-
lized, the residence duration, and the amount of heat produced all have a
role in astaxanthin degradation during milling. Feed mixing is necessary
to achieve consistent nutrient distribution, resulting in a uniform nutri-
ent component in each fish pellet as a result of the formulation. Because
homogenization may introduce air into the mixture, resulting in undesired
carotene oxidation [48], using a vacuum mixer to curtail air exposure as a
method of eliminating air entering the mixture is a smart way to proceed.
In addition, secondary antioxidants have been shown to improve the oxida-
tive stability in dietary carotenoids during feed production. Extrusion, on
the other hand, is used in feed processing to increase starch (gelatinization)
and protein digestibility while reducing food component degradation [49].

It’s also a great way to make floating or sinking pellets by adjusting the rec-
ipe. Extrusion technique, on the other hand, includes significant amounts
of mechanical shear, heat, pressure, and moisture, most all of which are
likely to affect the stability of carotenoid pigments [50].
4.3.3 Alga as a Potential Source of Astaxanthin and Food

Supplement
The green single-celled freshwater alga, Haematococcus pluvialis, has been
found to be an intense maker of astaxanthin and a primary hotspot for
human utilization. For many years in the Asian nations, the green min-
iature algae have been utilized as a food origin or nutritive enhancement.
These days, all the world consumes them for their health advantages. The
green algae Haematococcus pluvialis, Chlorella vulgaris (Chlorophyceae),
Cyanobacteria Spirulina (maxima) and Dunaliella salina are probably the
most biotechnologically significant microalgae, and are generally utilized
and popularized predominantly as human nourishment enhancements
and as added substances in feed for animals [29]. There is a blue-green alga
known as Spirulina platensis. This alga is acquiring overall acceptance as a
supplement for food, being perhaps the most nourishing food known by
man. Alga has been demonstrated to be an astounding origin of colors [51,
52], proteins nutrients and phenolics [53] and polyunsaturated fatty acids
[54]. Currently, Spirulina has been noted to be significantly utilized for the
extraction of the blue photosynthetic color, especially phycocyanin [55].
Dunaliella salina is another significant microalga under current devel-
opment. This species was developed as an origin of beta-carotene and as
the photosynthetic shade. Beta-carotene is utilized as a vitamin C enhance-
ment and an orange color. Currently, the microalgal business is over-
whelmed by Spirulina and Chlorella [56, 57], fundamentally on account
of their ease of cultivation as well as their high nutritive worth and protein
content. The energy source of these algae is showcased as pills, fluids and
containers; and utilized for nutrition enhancement. A practical oil food,
plenteous in antioxidants and unsaturated fats, pigmented with colors
(carotenoids), separated with CO2 that is supercritical, was delivered from
a microalga, Chlorella vulgaris, with its prospective utilization in the food
business particularly for seafood derivatives [20].
Microalgal pigments have profitable uses as an unprocessed food col-
oring and beautifying constituent. Some microalgae contain noteworthy
measures of carotene (other than beta-carotene). Various shades of color
are also seen in microalgae. Usually, beta-carotene is utilized as a pigment-

ing substance (specifically applied in giving the yellow pigment to mar-
garine), as a food added substance to upgrade the shade of the tissue of
fish and the yolk of eggs, and to work on the wellbeing and productive-
ness of cows fed with grains. The hidden capability of miniature algae as
a wellspring of food coloring is restricted, though, on the grounds that
algal derivative food coloring isn’t photostable and the color will generally
blanch with cooking. Nonetheless, regardless of this restriction, the possi-
ble market for miniature alga derivative food coloring is tremendous [12].
For instance, Dunaliella salina produces significant beta-carotene, and
it is cultivated to serve as an origin of photosynthetic color. β-Carotene,
other than being one of the main food colorants as recently referenced, has
solid antioxidant amplitude which assists in the intervention of the harm-
ful impacts of free radicals ensnared in different ailments like many types
of gastrointestinal malignant growth, joint inflammation, or untimely
maturing brought about by bright radiation [58]. Furthermore, β-carotene
may well upgrade resistance contrary to different nonresistant ailments.
Nevertheless, β-carotene has been expressed to be capable of functioning
as a pro-oxidant during the course of peroxidation of lipids, when both
oxygen strain and carotenoid consolidation is high [59].
4.3.4 Technological Application of Algae as Origins of

Supplements and Bioactive Mixtures in Healthier Food
Varieties and Drinks
The presence of different supplements and bioactive mixtures from algae
in a food could be a source of natural functional enrichment; likewise, the
mechanical fortuity offered by algae in the reformulation of food products.
This explains algae’s effectiveness as normal constituents in reformulation
procedures for quality drinks and food production, as well as functional
food varieties [60]. The improvement of functional food sources offers tre-
mendous opportunities in the food and drink industry. The utilization of
algae as elements in quality food and drink inventions offers fascinating
potential outcomes. Novel healthy foods should be visible as a chance to
provide for the needs of consumers, and furthermore to refresh sugges-
tions (concerning supplement and dietary objectives) [61].
Algae, a food variety of low-energy, consists of a varied assortment of
compounds with helpful wholesome and mechanical properties. It also
contains bioactive substances with possible diverse utilitarian proper-
ties when consolidated into the frameworks of drink and food sources.
Contrasted with the consideration of algae extracted mixtures, the utiliza-

tion of the entire algae in drinks and food manufacturing offers a method
for concurrently connecting various parts (dietary fiber, protein, miner-
als, nutrients, carotenoids, polyphenols, and so forth) in a way that doesn’t
include the arduous, costly and ecologically unpleasant sanitization and
extraction procedures that are required whenever these parts are utilized
independently. An extensive assortment of algae has been utilized for
numerous purposes in food (dairy, meat, pastry shop, fish, pasta and dif-
ferent items) and drinks preparations. The inclusion of these algae in food
such as meat foods unlocks fascinating new possibilities for the utilization
of algae in the plan of better muscle-based food products, as well as the
chance of conquering mechanical issues related with low-salt foods [36].
In addition, there has been a significant amount of attention on water
algae as useful food sources to decrease certain health risks, and the epi-
demiological evidence linking routine algae utilization to a lower risk of
heart diseases. Although a few parts of algae like polyoses (alginates, car-
rageenates, and agar) have been utilized for innovative drives in the food
business for quite some time, as of late, they have been utilized more as tex-
turing and bulking mediators (because of their physicochemical proper-
ties), especially in the production of food sources with low calories. Algae
is utilized in the definition of better meat items to beat mechanical issues
(connected with water and fat restricting properties and surface) related
with low-salt issue. Complete algae can be added to food sources to exploit
their wholesome, functional and mechanical properties. As a sole constitu-
ent, the consolidation of entire algae inclines toward the synchronous exis-
tence of various constituents (protein, minerals, polyphenols, nutrients,
dietary fiber, carotenoids, and so on), together with their advantageous
health impacts as well as innovative benefits. Algae are appropriate regular
specialists for conveying bioactive substances in an extensive assortment
that conceivably possess multifarious useful characteristics in connection
with the frameworks of food and drink sources [62].
Functional parts of algae have been utilized in the detailed arrangement
of specific substances or as components of elements like vegetable concen-
trates, flours, food fibers, spices and flavors, probiotics, plant and marine
oils, and so on. Likewise, they are useful in upgrading dietary benefit, pro-
viding medical advantages and conferring helpful innovative and tangible
qualities in light of various issues related to reformulation processes [63].
The alga U. pinnatifid is being considered for further development for its
water-restricting characteristics in burgers, thereby helping with issues
connected with lower salt content [53]. Ocean spaghetti (Himanthalia elon-
gata), an eatable earthy colored alga, has been utilized as a utilitarian fixer
in various meat items; 5% of H. elongata has been utilized in the process of

redesigning low-fat or low-salt sausages with firmer and chewier textures
and improved water- and fat-restricting characteristics, which very well
may be utilized in other lower salt items in order to forestall quality imper-
fections because of a low salt fixation.
The incorporation of red alga (Porphyra umbilicalis) in meat items raises
the content of protein, likewise the strata of a few amino acids like glycine,
alanine, tyrosine, arginine, valine, serine and phenylalanine. Laminaria
japonica (1–5%) has been utilized as a replacer of fat in low-fat pork patties
with practically no unfavorable effects observed in the nature of the meat
by consumers. Integration of L. japonica improved textural and physical
characteristics of meat patties, expanded the fiber of the diet, and dimin-
ished cooking failures [64]. Kappaphycus alvarezii is known to have con-
structive outcomes in enhancing minerals, prompting a decrease in the
problems associated with cooking, and an expansion in patties’ taste [65].
Prabhasankar et al. [66] examined the impact of U. pinnatifida introduced
at various levels (0–30%) on the tangible, cooking, nourishing and bio-
functional nature of pasta, announcing that pasta consisting of about 20%
algae had satisfactory tactile qualities and enhanced biofunctional charac-
teristics. Pasta containing added algae brought about superior amino cor-
rosive and unsaturated fat outlines, higher entire phenolic substance and
cell reinforcement activity as well as developed fucoxanthin and fucosterol
material.
4.3.5 Enriching Dairy Products with Algae

Dairy products have similarly been enriched with algae. For instance, indi-
viduals lacking casein-debasing catalysts can’t reingest calcium from dairy
products, hence foster some sort of hypocalcemic reaction. The incorpora-
tion of calcium-rich green algae could expand its focus in items from dairy.
Algae have been consolidated into various sorts of cheese. Curds (simple
and economically created) were produced with 3, 9 and 15% respectively
from L. japonica and U. pinnatifida, the cheddar with 0.5% Chlorella was
preferred (ideal tactile boundaries) to the 1% Chlorella, and enhanced the
surface and color [67]. Additionally, Heo et al. [68] explored the impact of
adding 0–2.0% of Chlorella powder on sensory characteristics, develop-
ment of lactic acid bacteria and maturing speed of Appenzeller cheddar.
Higher lactic acid bacteria were observed in the cheddar with added algae
than in the control.
4.3.6 Algae as a Potential Healthy Protein and Fat Source

Microalgae stood out as a capable sustainable substitute of protein source.
Several proteins, amino acids and peptides from Algal have been reported
to have beneficial effects to combat binding of mineral, programmed cell
death, cell differentiation of cancer cells, metastasis, anti-human immuno-
deficiency virus activities, inhibition of human platelet accumulation and
lipase activities reticence among others [60].
Microalgae is an important origin of ω-3 PUFAs. Dunaliella, Arthrospira,
Haematococcus, Chlorella, Schizochytrium, Crypthecodinium cohnii and
Porphyridium cruentum have GRAS status. Tetraselmis chuii also could
serve as a seafood seasoning operator; as well as Odontella aurita, the dia-
tom is now being eaten as additive in food rich in EPA. Some food deriv-
atives of microalgae showcased DHA from C. cohnii, β-carotene from
Dunaliella, and the blue colorant phycocyanin from Arthrospira among
others [69]. For example, the cost of items such as phycocyanin, astax-
anthin, and β-carotene ranges from hundreds to thousands of euros for
every kg contingent upon their cleanliness; also, the top tier they draw in
the marketplace caused industries to be extremely desirous of them. Then
again, entire microalgae cells as food enhancements are available under
40 e for every kg [55]. Likewise, products derived from microalgae with
biofunctional compounds that cost more than normal food enhancements
can probably expand on their commercial possibility. The greater market-
ing costs would permit taking care of greater expenses resulting from new
propagation and handling machineries.
Other than supplying supplements and energy for organism upkeep,
development, and active work, food varieties can be a vehicle for con-
veying bioactive mixtures with health advantages. Among the various
sorts of compounds derived from microalgae, the ones having antioxi-
dant abilities are likely the most intriguing ones for modern applications.
Aside from being a decent origin of proteins, Arthrospira, Chlorella and
Nannochloropsis have been accounted for as significant wellsprings of oli-
gosaccharides or polysaccharides, as they are projected as potential pre-
biotic competitors. Other derived compounds from microalgae and the
entire cells have been utilized as food constituents with various intents.
Khemiri et al. [70] and Niccolai et al. [71] noticed constructive outcomes
on the techno-utilitarian as well as the antioxidant characteristics of food
emulsions following addition of certain microalgae species. Gels continue
to be proposed as a means to give significant compounds derived from
microalgae. Batista et al. [72] added a few animal types of microalgae into
gels to work on their construction as well as a method for giving cell rein-
forcements and certain ω-3 PUFAs to possible customers. Comparable
investigations introducing other species of microalgae were accounted.
Chlorella has been effectively introduced into cheeses and yogurts [73].
Cookies and biscuits have been found to be applicable classifications to
convey constituents derived from microalgae such as astaxanthin. Motives
involve great acknowledgment of taste, flexibility, advantageous ingesting
because of their simplicity of protection and conveyance, outward form
and surface. Though addition of Chlorella vulgaris in cookies has proven to
be an operator for pigmentation and possibly as an antioxidant and food
enhancement, incorporation of Isochrysis galbana furnished cookies with
ω-3 PUFAs valuable for human health. Likewise, addition of phycocyanin
concentrates and entire A. platensis to formulate cookies provided cook-
ies with possible health advantages, improved protein and fiber constitu-
ents [53, 72]. Batista et al. [72] reported improved nourishing and healthy
support capability of cookies, thus expanding protein and antioxidants
elements, by introducing Tetraselmis suecica, A. platensis, Phaeodactylum
tricornutum and C. vulgaris. Addition of Haematococcus pluvialis into
cookies also brought down the glycemic reaction and expanded the limit
in antioxidant levels.
Another product similar to cookies is bread, which is likewise generally
eaten. Some years back, a few researchers declared microalgae from astax-
anthin integration into bread in order to improve its nourishing character-
istics. In previous years, prior to being added to white bread produced from
wheat, Dunaliella was recommended as a protein supplement in bread.
In order to build its protein content, Arthrospira and a bleached extract
acquired from this species were additionally integrated in bread. Likewise,
other species of microalgae were utilized in bread. Ongoing accounts sim-
ilarly referenced the incorporation of microalgae in bread without glu-
ten; incorporation of Arthrospira altogether expanded protein constituent
and further developed quality of bread because of the existence of a few
fundamental amino acids contrasted with bread which is non-enhanced.
Comparable advantages were seen when Arthrospira was utilized as con-
stituents in extruded appetizers [74, 75].
Another product that astaxanthin is generally acknowledged for and
incorporated into is pasta. Addition of both Arthrospira maxima and C.
vulgaris improved the healthful constituents of new spaghetti, with an
all-around acceptability of the product by the panel set up for the sen-
sory evaluation. Pasta likewise provided a means to convey ω-3 PUFAs
and antioxidants with latent health advantages. In spite of the fact that
Arthrospira expanded the protein ingredients, protein edibility diminished

as the microalgae constituent expanded [76, 77].
The techno-useful properties of astaxanthin regulate the appropriate-
ness of added substances in food items. For example, properties like froth-
ing, gelation, emulsifying, fat, and water retention limits are accounted
for in some hydrolysates and proteins of microalgae. Spirulina platensis
showed antiviral activity against different infections, such as human cyto-
megalovirus, herpes simplex and measles, by obstructing their entrance
because of the existence of sulfur-containing polysaccharide. Microalgae
obviously express a likely capability of addressing the requirements for
extra sustainable nutrition arrangements for the populace. The extrava-
gance of composites in microalgae can foster a food industry that is algal
based, and concerned with delivering and using microalgae for creative
utilitarian food items. Other than the constituent of protein and adjusted
profiles of the amino acids, consolidation of microalgae into food varieties
could prompt possible advantages for human health because of the bio-
active mixtures that are present in some species of microalgae. The use of
items produced from microalgae-inferred or microalgae as substitutes for
food isn’t inexpensive yet, essentially because of the short TRL as well as
absence of the shrinking economy for the propagation of microalgae and
its handling [78].
4.4 Future Perspective

The utilization of bioactive compounds as food components has become
necessary due to rising health concerns and lifestyle changes. Carotenoids
have a bright future in this regard. Cancers, high blood pressure, diabe-
tes, cardiovascular, digestive, hepatic, neurological, and skin disorders
have showed positive signs when astaxanthin is introduced. Its antioxi-
dant capabilities are utilized to protect sick cells from oxidative damage.
Astaxanthin’s high antioxidant effects and biological stability have been
demonstrated in several studies and have applications in numerous fields.
Astaxanthin is a nutrient that can penetrate cell membranes and has pos-
itive impacts on cells. It is utilized as a targeted medicine to scavenge free
radicals at specific places via a carrier; as a powerful antioxidant to shield
cells from oxidation damage, and so on. Astaxanthin has prospective appli-
cation value in treating diabetes which is based on these benefits. As a result,
the utilization of carotenoids as a nutraceutical, pharmaceutical agent, and
nutritional supplement in the worldwide market might be a positive move
for humanity. Though acceptability and restriction are challenges that
must be overcome; when these hurdles are cleared, integrating astaxan-

thin and carotenoid from microalgae as components of food won’t just give
therapeutic advantages, but will likewise add to further developing issues
connected with supportability, considering the developing populace and
our present eating regimen, propensities, and wellbeing.
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5
Production of Polyunsaturated Fatty Acids
(PUFAs) and Their Biomedical Application
Olorunsola Adeyomoye1*, Olugbemi T. Olaniyan2 and Charles O. Adetunji3
Department of Physiology, University of Medical Sciences, Ondo City, Nigeria

1
2
Laboratory for Reproductive Biology and Developmental Programming,
Department of Physiology, Rhema University, Aba, Nigeria
3
Applied Microbiology, Biotechnology and Nanotechnology Laboratory, Department
of Microbiology, Edo State University Uzairue, Iyamho, Nigeria
Abstract
Polyunsaturated fatty acids (PUFAs) are a unique class of food constituents that
serve a variety of biological functions. Because of a growing awareness of their
potential to improve diet and human health, these compounds have received
worldwide attention in recent years. Microbial cell biotechnologies are an import-
ant solution for supplying these biomolecules in sufficient quantities, as well as
supplying PUFA-rich aquafeed, superfoods, and medical formulations. Their ther-
apeutic and pro-health effects have already been demonstrated in a variety of dis-
eases, including cancer, neurological disorders, cardiovascular disease, diabetes,
obesity, and others. The various classes of PUFAs are discussed in this chapter,
as well as their production and therapeutic potential in natural food sources and
through genetically engineered microalgae cultivation.
Keywords: Polyunsaturated fatty acids, microbial cell biotechnologies,

human health, food sources, cancer
5.1 Introduction
Polyunsaturated fatty acids (PUFAs) made from hydrocarbon chains are
known to contain two or more bonds. They are of benefit to human health
125
and are also present in plants. They are also concentrated in microbes
and a large collection of PUFAs are made through microbial engineering
[1]. Polyunsaturated fatty acids are classified in line with their chemical
composition which include conjugated fatty acids, methylene-interrupted
polyenes, and other PUFAs. They could as well be divided into two groups
according to their length of carbon backbone. These include short-chain
with 18 carbon atoms and long-chain with 20 or more carbon atoms.
Arachidonic and docosahexaenoic acids are precursors to dietary polyun-
saturated fatty acids, linoleic acid, and linolenic acid [2]. Polyunsaturated
fatty acids have been linked to enhanced neurological and cognitive devel-
opment [3]. PUFAs have been shown to reduce blood triglyceride levels
through increase in oxidation of fatty acids by PPAR activation or by reduc-
ing SREBP-1 activity, which inhibits lipogenesis [4]. Dietary PUFAs cause
lipid oxidation and decrease insulin resistance through the activation of
PPAR-α, which also results in reduction in hepatic steatosis [5]. Evidence
from human and animal studies has shown that PUFAs play a role in pre-
vention and management of diabetes, obesity, cancer, and heart diseases
[6]. Corn, safflower oils, flaxseed, fish and soy are sources of PUFAs.
5.2 Polyunsaturated Fatty Acids

At least two bonds are present in the backbone of polyunsaturated fatty
acids. They also have essential substances which are responsible for prop-
erties of the oils. Ingredients such as essential acids and those that are
responsible for the different properties of dried oils are contained in them
[7]. The type of PUFA is determined largely by the shape of the first dou-
ble bond in relation to the methyl end of the fatty acid. Double bonds are
usually of cis configuration. The trans fatty acids consist of approximately
2–5% of fatty acids present in soluble milk and meat, and 5–20% of fatty
acids present in hydrogenated fats [8]. PUFAs possess amphipathic prop-
erties, which means they possess a head (hydrophobic) and tail (hydro-
philic). Hexadecatrienoic acid, alpha-linolenic acid, stearidonic acid,
tetracosapentaenoic acid, and heneicosapentaeno acid are some examples
of omega-3-series PUFAs. Omega-6 series includes eicosadienoic acid,
dihomo-gamma-linolenic acid, arachidonic acid, adrenic acid, tetracos-
apentaenoic acid, and docosapentaenoic acid. Mead acid, erucic acid,
oleic acid, eicosenoic acid, and nervonic acids are all part of the omega-9
series. Rumenic acid, calendic acid, parinaric acid, and others are conju-
gated fatty acids. PUFAs are precursors of body metabolites. Arachidonic
acid, for example, is a precursor to prostanoids series 2 and leukotrienes
Production of PUFAs and Their Biomedical Application 127
series 4. In addition, the metabolism of eicosapentaenoic acid and docosa-

hexaenoic acid produces a series of prostanoids 3 and leukotrienes series
5 [9]. Many of these compounds possess anti-inflammatory, antiplatelet,
and antiarrhythmic properties, according to research [10]. Other functions
include maintaining cell membrane fluidity, reducing macrophage release
of proinflammatory cytokines, enhancing vascular endothelial cell func-
tions, and reducing triglyceride synthesis in the liver [11].
5.3 Production of Polyunsaturated Fatty Acids

Polyunsaturated fatty acids from fish oil, particularly arachidonic acid,
eicosapentaenoic acid, and docosahexaenoic acid, are valuable dietary sup-
plements with numerous health benefits. PUFAs production from fish oil
had decreased in the last decade due to overfishing and ocean pollution.
Some microalgae species have also been identified as ideal producers of
LC-PUFAs because they naturally accumulate large amounts of LC-PUFAs
by using CO2 and light energy [12]. A growing set of genetic tools is also
available for the creation of high-performance strains of microalgae, with
increased efficiency in the production of fatty acids and their derivatives.
Triacylglycerols accumulate in microalgae which are mainly composed of
monounsaturated fatty acids and saturated fats [13]. The red microalga
of Porphyridium cruentum TAGs shows high arachidonic acid and eicos-
apentaenoic acid content. This algae variability was impaired at lower
temperatures with lower levels of eicosapentaenoic acid and monogalacto-
syldiacylglycerol. In contrast, Green TAGs can grow at low temperatures,
with lots of arachidonic acids. An arachidonic acid was stored at 25 °C
for 12 hours. This labeled arachidonic acid was transferred from TAGs to
polar lipids with increased yield at low temperatures. The use of microal-
gal in producing polyunsaturated fats has continued to yield promising
results. Phaeodactylum tricornutum, a genetically modified microalgae,
have been shown to accumulate PUFAs with arachidonic acid and a
docosahexaenoic acid content of 18.98 g/mg and 9.15 g/mg, respectively
[14]. Eicosapentaenoic acid levels reached a maximum of 85.35 g/mg.
Arachidonic acid and eicosapentaenoic acid can both be formed from tri-
acylglycerides, while docosahexaenoic acid is made only in phospholipids.
The combination or expression of many enzymes has the potential to pro-
duce stable PUFA [15]. PUFA is also found in vegetable seeds, fish oil, and
filamentous fungi. Mortierella alpina, a filamentous fungus, is capable of
producing triacylglycerols that are rich in arachidonic acids, with concen-
trations of up to 20 g/l [16]. For the exploitation of genes of M cells alpina
strains has shown great promise in PUFA biosynthesis and specification of

the activities of their enzymes [16].
5.4 Nanomedicine-Based Formulations Containing

Polyunsaturated Fatty Acids
Omega-3 polyunsaturated fatty acids are a dietary component and have
been linked to the prevention of heart disease, inflammation, and cancer
[17]. A multidisciplinary approach has been developed to produce omega
3-containing nanoformulations with the aim of protecting these fatty acids
from degradation, thereby increasing their availability, bioactivity and
transport to tissues [17]. These nanoformulations were created to provide
omega-3-PUFA in combination with other medications. Omega 3-PUFAs
are obtained from diet due to the inability of the body to synthesize them.
The increased oxidative stability of ω-3-PUFAs, along with their decreased
bioavailability and bioactivity in targeted tissues, is a barrier to determin-
ing their therapeutic potential. ω-3-PUFA-rich-in-water nanoemulsion
formulation was used to enhance the delivery of 17-β-estradiol and C6
ceramide payload to adult blood cells [18]. ω-3-PUFA-rich nanoemulsion,
as well as CER given nanoemulsion have been shown to inhibit the growth
factor that stimulates cell proliferation with increase in pro-apoptotic
caspase 3/7 activity. The mitogen-induced protein kinase signal reduced
VSMC proliferation while improving endothelial cell increase in the loaded
17-β-estradiol nanoemulsion. The antiproliferation effect of 17-β-estradiol
and C6 ceramide laden nanoemulsions was more pronounced in VSMCs
than in the endothelial cells. These biological applications of ω-3-PUFA, C6
ceramide, and 17-β-estradiol experiments of nanoemulsion are acceptable
for the approach developed in animal models of occlusive vasculopathies.
During experiment on atherosclerosis, the impact of novel ω-3-fatty-rich,
17-β-estradiol, CREKA-peptide-modified nanoemulsion system were tested
[19]. The 17-β-estradiol nanoemulsion technology in combination with
CREKA-peptide-modified nanoemulsion was shown to enhance cellular
nitrate/nitrite in endothelial cells, which indicates an improved produc-
tion of nitric oxide. The systematic administration of this nanoemulsion
in ApoE-/-mice feeding on a high-fat diet developed problems related
to occlusive atherosclerotic vasculopathy. The 17-β-estradiol and ω-3-
polyunsaturated fatty acid constituents of a nano delivery system have
been found to be biocompatible, and act as a measurement of body weight,
plasma levels of alanine aminotransferase/aspartate aminotransferase, and
assessing the histology of the liver and kidneys, at therapeutic doses. The
distribution profile and pharmacokinetic of 17β-estradiol in wild-type
C57BL/6 mice, and system delivery using cationic or CREKA-peptide-
modified omega-3-fatty acid oil containing a nanoemulsion system was
investigated [20]. When administered, 17-β-estradiol was shown to accu-
mulate in the heart, aorta, liver, and kidneys. In the wild version of C57BL/6
mice, the CREKA-peptide-modified nanoemulsion system was found to
be the best 17-β-estradiol system management vehicle.
5.5 Biological and Medical Application

of Polyunsaturated Fatty Acids
Polyunsaturated fatty acids form various components of fats because of
their unique properties and function in the diet. Their therapeutic poten-
tial has been demonstrated in many inflammatory and autoimmune dis-
orders which include changes in lipid production, gene expression, and
signal transduction [21]. Aurantiochytrium sp. strain was used to remove
dissolved organic carbon and nitrogen in boiling bean sprouts and miso
processing during which PUFA was produced. This strain removed 52%
of dissolved organic carbon and 37% of dissolved nitrogen in boiling bean
contaminated water, thereby producing a biomass that contains 137 mg/g
of fatty acids, which also include 96.2 mg/g of docosahexaenoic acid [22].
The growth of this strain of microalgae in stagnant polluted water also
caused increase in biomass that contains 147.6 mg/g of fatty acids, which
include docosahexaenoic acids, as well as 47% removal of dissolved car-
bon and 55% removal of dissolved nitrogen. These results from numerous
findings showed that microalgae are capable of producing polyunsatu-
rated fatty acids when used in removing organic substances from polluted
wastewater. The applications of these polyunsaturated fatty acids have
widely been reported. Omega-3 fatty acids have been reported to influence
dopaminergic and serotonergic pathways in the central nervous system.
Omega-3 fatty acids are produced and used as treatment for many neuro-
logical disorders [23]. The application of omega-3 fatty acids in the man-
agement of schizophrenia, psychiatric disorder, anxiety disorder, major
depressive disorder, attention deficit hyperactivity disorder, psychiatric
disorders, obsessive-compulsive disorder, post-traumatic stress disorder,
autism spectrum disorders, and eating disorders was shown by data gen-
erated on the efficacy and tolerance of omega-3 fatty acids in psychiat-
ric disorders published between 1980 and 2019 [23]. Omega-3-fatty acids
have shown great effectiveness in the treatment of depressive symptoms in

patients with severe bipolar depression. During early stages of schizophre-
nia, in addition to antipsychotic treatment, some success was recorded, but
not in the chronic stages of psychosis following fatty acid administration.
Minimal beneficial effects of omega-3 fatty acids in attention deficit hyper-
activity disorder were seen, and positive effects on major BPD symptoms
were reported in a few trials. The anticancer properties of linolenic acid
and dihomo-linolenic acid have been investigated, including their alter-
ation of cell apoptotic changes and inhibition of cell proliferation [24].
Furthermore, human studies have revealed a relationship between high fish
oil consumption and a lower risk of colon, prostate, and breast cancer, even
though some other studies have not found a significant link. Despite this,
the available epidemiological evidence, when combined with the effects
caused by fatty acids on animal cancer and cell culture models, has encour-
aged the production of clinical therapeutic interventions that incorporate
n-3 PUFAs in cancer prevention and treatment, in addition to nutritional
support. Polyunsaturated fatty acids have resulted in loss of weight and
balance of immune system in the cancer patient. The biotransformation of
omega-3 and omega-6 PUFA produces a series of lipid metabolites that are
capable of bringing about cellular processes. The lipid metabolites present
in omega-6 PUFA have been linked to a variety of biological properties,
which include the development of a variety of clinically approved medi-
cations, including latanoprost, which is an essential medication [25]. In
addition, evidence suggests that omega-3 PUFA may simply act as compet-
ing substrates for enzyme biotransformation and reducing the production
of omega-6 PUFA-derived lipid metabolites [26]. The effects of different
dietary concentrations of omega-3 and omega-6 PUFAs on brown adipose
tissue in type 2-induced diabetic mice was investigated. At lower concen-
trations, these fatty acids significantly increased the mass of brown adipose
tissue by 67.55% and 60.49% respectively. In addition, they decreased total
cholesterol, low-density lipoprotein, fasting blood sugar, and triglyceride,
and increased sugar tolerance [27]. The assessment of qRT-PCR showed
that low omega-6 and omega-3 PUFA activated brown adipose tissue with
increased expression of Ucp1, PPAR-α, cAMP, GLU1, HSL, LPL, lipid and
glucose metabolism in diabetic mice. Many other applications of PUFAs,
particularly omega-3 and omega-6 PUFAs, have been reported in the liter-
ature. The aforementioned therapeutic potentials of PUFA were based on
research conducted on animal and human experimental models. Therefore,
incorporating them in the diet may have health benefits and help prevent
the development of many diseases.
5.6 Metabolism of Polyunsaturated Fatty Acid

Polyunsaturated fatty acid metabolism was analyzed using isolated cells
from cardiomyocytes, lymphocytes, fibroblast as well as hepatocyte of mice
[28]. Dietary and hormonal factors were shown to affect the activation of
fatty acids, which determines whether the fatty acids have been cleared,
chain-longated, directly esterified, or oxidized [29]. In both mice and
humans, short-term and long-term regulation of dietary fats have been
investigated. There are important differences in fatty acid esterification,
oxidation, and fatty acid formation in lipoproteins. This discrepancy is said
to be due to at least changes in protein concentrations that bind intracel-
lular fatty acids in the liver [30]. The modification of the peroxisomal ret-
roconversion of unsaturated fatty acids to its homologues is said to play a
role in regulating fatty acid formation in phospholipids bilayer membrane.
Many patients with various disorders of lipids do not have peroxisomes or
are deficient in peroxisomes. The beta-oxidation of very-long-chain acids
is affected in a few peroxisomal disorders. The strength of fibroblasts in
people with Zellweger disease, peroxisomal disorders, X-linked adreno-
leukodystrophy and adrenoleukodystrophy to degrade fatty acids varies.
In the brain, docosahexaenoic acid is rich in omega-3 fatty acids which
regulates very important functions and acts as precursor of bioactive
metabolites [31]. The presence of docosahexaenoic acid in the brain is reg-
ulated by a number of processes that leads to its utilization and metabo-
lism. Docosahexaenoic acid in the brain is absorbed and re-digested in the
membrane phospholipids, leading to the distribution in the brain. During
neurotransmission, docosahexaenoic acid is released from membrane
phospholipids and converted to bioactive metabolites that controls signal-
ing pathways that are important for synaptogenesis, neuroinflammation,
and cell survival, and also help in the treatment of neurological disorders.
In the liver of mice, metabolism of double bonds delta-3 fatty acids was
investigated [32]. Subcellular fractionation tests showed the presence of
peroxisomal and mitochondrial delta 3, the activity of delta-2-enoyl-CoA
isomerase following the introduction of delta-3-trans-dodecenoic acid
into the liver. These observation in line with previous finding of peroxiso-
mal 2, 4-dienoyl-CoA reductase, suggest that peroxisomes contain all nec-
essary beneficial enzymes needed for beta-oxidation of unsaturated fatty
acids. Peroxisomes can oxidize a variety of substrates, which include (poly)
estoy-free unsaturated estoy-CoA esters. Furthermore, in peroxisomes and
mitochondria, beta-oxidation of unfilled enoyl-CoA esters involves chain
shrinkage, and also the use of metabolizable double carbon-to-carbon
bonds [33]. Auxiliary enzymes such as delta 3, delta 2-enoyl-CoA isom-

erase, 2,4-dienoyl-CoA reductase, 2-enoyl-CoA hydratase 2 or 3-hydroxy-
acyl-CoA epimerase, and delta 3,5 delta 2,4-dienoyl CoA isomerase are
necessary for fatty acid metabolism in addition to beta-oxidation spiral
enzymes. There are different isoforms of these enzymes and they can be
found in various subcellular compartments that include mitochondria,
peroxisomes, and endoplasmic reticulum [34]. Subcellular distribution of
delta 3,5, delta 2,4-dienoylCoA isomerase was demonstrated in rat liver
peroxisomes. The peroxisomal and mitochondrial isomerase was shown
to have the same specificity and are homologous, as evidenced by the anti-
sera produced against the peroxisomal enzyme [35]. Peroxisomes con-
tain all the necessary enzymes required for beta oxidation of fatty acids
with unique numbers of bonds and NADPH-dependent 2,4-dienoyl-CoA
reductase which removes the double bonds by reduction process [49].
5.7 Challenges and Issues of Production

and Use of Polyunsaturated Fatty Acids
There has been remarkable progress over the past few decades in the pro-
duction and use of polyunsaturated fatty acids. However, new evidence has
emerged stating that there are challenges concerning the bioavailability
and use of PUFA in aquatic environments and humans [36]. The content
of PUFA in microalgae has become an important measure of the quality
of algae nutrients for consumers. Cryptophyceae and Dinophyceae have
been shown to have increased levels of eicosapentaenoic acid and doco-
sahexaenoic acid, making them ideal as food for zooplankton [37]. In
contrast, Chlorophyceae, a green algae and cyanobacteria, did not contain
long-chain PUFAs but high levels of ALA, a short-chained fatty acid with
low nutritional value [38]. This implies that not all algae serve as a source
of nutrients for aquatic organisms, so some of them are not a source of
high-quality food. Eicosapentaenoic acid and docosahexaenoic acid play
an important biochemical and physiological role in humans and many
animals. All vertebrates and most invertebrates require these long-chain
PUFAs. Most animals do not have the capacity to combine eicosapentae-
noic acid and docosahexaenoic acid in the short chain, so they have to
get these long-chain PUFAs into their diet. In addition, people who do
not eat fish cannot have their main source of eicosapentaenoic acid and
docosahexaenoic acid as fish. Other long-chain PUFA dietary sources that
provide eicosapentaenoic acid and docosahexaenoic acid with a limited or
near value should be available to such individuals [39]. Polyunsaturated

fatty acids have been shown to be more prone to oxidation during heating.
Therefore, in the literature, the breakdown of long-chain PUFAs in the diet
has been reported during cooking as well as other therapeutic modalities.
5.8 Conclusion
Polyunsaturated fatty acids are commonly found in a variety of dietary
sources with significant health benefits. Microalgae cultivation has con-
tinued to accumulate these compounds in many areas. In addition, these
polyunsaturated fatty acids have been used as part of the formulation for
the management of several diseases. Recent advances in the use of bio-
technologies in the cultivation of microalgae can improve the efficiency of
production and utilization of these compounds [40–48].
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6
Utilization of Algae and Their
Anti-Proliferative and
Anti-Inflammatory Activities
Olorunsola Adeyomoye1*, Olugbemi T. Olaniyan2 and Charles O. Adetunji3
1
2
3
Applied Microbiology, Biotechnology and Nanotechnology Laboratory,
Department of Microbiology, Edo State University Uzairue, Iyamho, Nigeria
Abstract
Algae are mostly aquatic, photosynthetic, and nucleus-bearing organisms with-
out the true roots, stems, leaves, and specialized multicellular reproductive sys-
tems found in plants. Many contain chemical constituents used in cosmetics,
pharmaceuticals, the food industry, manure, and different food supplements.
Their metabolites have been utilized to treat a variety of cancers due to their cyto-
toxic, antiproliferative, and apoptotic properties. They have been shown to pos-
sess anti-inflammatory phytochemicals that can be employed as treatments or in
the development of structural analogs with strong anti-inflammatory properties.
Algae also have additional uses, such as the development of algae-based nano-
composites for heavy metal removal and the formation of biopolymers for diverse
materials. This chapter introduces algae, its properties, and the possible health
benefits of algae biocomposites.
Keywords: Algae, nanocomposite, antiproliferative, anti-inflammatory,

biopolymers
139
6.1 Introduction
Algae are groups of photosynthetic organisms that range from unicellu-
lar microalgae, such as Chlorella, Prototheca and Diatoms, to multicellu-
lar forms such as giant kelp. They are found in aquatic environment and
can synthesize organic compounds such as carbohydrates, fats and pro-
teins. Many of them are devoid of stem, xylem and phloem seen in land
plants. Seaweeds are marine algae, such as Rhodophyta, Phaeophyta and
Chlorophyta macroalgae, which are multicellular in nature. Algae are also
found in freshwater, examples of which include Spirogyra and stonewort.
Other algae groups include Zygnematales, euglenoids, cryptomonads,
chrysophytes, dinoflagellates, and cyanobacteria [1]. Many of them have
the capacity to live in extreme weather conditions and acidic environ-
ments. They are primary producers with different colors and are mem-
bers of other eukaryotes such as the viruses, bacteria and fungi. They are
present in snow environment and help in melting of snow packs and for
the surveillance of climate change [2]. Algae have been shown to increase
the production of secondary metabolites such as astaxanthin and pur-
purogallin, which help protect chloroplast and nucleus from the cellular
damage from ultraviolet radiation. Algae have several applications in the
food industry due to their chemical composition [3]. Algae can act as food
supplements and can be added to meat product such as sausages, pasties
and frankfurters. It is also added to cereal products to improve their qual-
ity. Fermented dairy products such as milk, yogurt, cheese and cream have
all been reported to contain algae [4]. Evidence has shown that cosmetic
products produced from algae may act as an anti-aging agent used for skin
whitening and reducing pigmentation [5]. Some algae have also been used
in formulating cosmetic products that are used for skin thickening and
moisturizing. Marine algae, such as the seaweeds, have been reported to be
useful in producing novel antidiabetic agents due to their bioactive com-
position [6]. The brown and green algae have been shown to exhibit anti-
diabetic potentials by regulating blood glucose level through inhibition of
carbohydrate hydrolyzing enzymes, insulin sensitivity and glucose uptake.
Bioremediation and biodegradation of wastewater contaminants have
been studied extensively using microalgae with resultant increase in bio-
fuels production [4]. In addition to the aforementioned applications, algae
biofuels are being considered as third generation biofuels. Several studies
have investigated the use of macro- and microalgae in producing biofuels
for economic sustainability [7]. Some of these biofuels include biosyngas,
bio-oil, biodiesel, and biohydrogen.
Utilization of Algae 141
6.2 Physiology and Biochemistry of Algae

Algae have the ability to produce toxins that can harm humans and ani-
mals, but they also provide a lot of benefits. They support fisheries and
other aquatic habitats and are a source of marine food webs. They are pho-
tosynthetic, meaning they take in CO2 and produce oxygen. Eukaryotic
algae can be found in either a haploid or diploid form. The life cycle of most
multicellular eukaryotic algae includes a sexual component, sometimes
with two or even three phases [8]. Cell division and cell separation are
required for asexual reproduction in unicellular algae. Asexual or sexual
unicellular phases, as well as fragmentation, are used in the reproduction
of colonial and multicellular algae [9]. Many eukaryotic microalgae (for
example, many diatoms and green algae) are known to reproduce sexu-
ally. Blue-green algae have a high amount of metabolic complexity despite
their simplicity. Their photosynthetic system, for example, is similar to that
of higher plants. Although the mechanism of these algae’s respiration is
unknown, many studies have described the effect of light on this process
in vivo [10, 11]. Light reduces oxygen intake at low levels but stimulates
it at high intensities. Chlorophyll enhances this effect, while photosystem
II inhibitor 3,4-dichlorophenyldimethyl-urea inhibits the stimulation [12].
Algae develop a variety of metabolites to assist them in dealing with the
harsh conditions of the sea. These compounds have recently attracted a lot
of interest for the identification of medicinally beneficial drugs, especially
those with potential anticancer properties, due to their structural diversity
and distinctiveness [12]. Included among the beneficial activities of algae
are their selectivity in inhibiting cancer cell proliferation over normal cells,
ability to kill cancer cells via non-apoptotic signaling pathways, ability to
bypass MDR-related efflux pumps, and efficacy in vivo in relevant pre-
clinical studies [13].
6.3 Algae Biocomposites

Biocomposites are materials composed of at least two distinct constituent
materials, both natural and synthetic, that are combined to produce a new
material with superior performance to the individual constituent materi-
als. Because of the environmental crisis and the issue of sustainability, there
has been an increase in interest in using natural resources to reinforce other
materials in recent years [14]. Algae is one of these natural resources that
can be used to strengthen diverse materials [15]. A red algae (Gelidium
Elegance) fiber was investigated as a biocomposite reinforcement. The

extracting and bleaching of red algae fiber was effective for both removing
mucilage materials and fiberization of red algae fiber. With a maximum
thermal decomposition temperature of 359.3 °C, bleached red algae fiber
(BRAF) exhibited very similar crystallinity to cellulose as well as higher
thermal stability [16]. Poly(butylene succinate) (PBS) biocomposites rein-
forced with BRAF were fabricated using a compression molding method
with varying BRAF contents, and their mechanical and thermal proper-
ties were investigated. With increasing BRAF content, the storage modulus
of PBS matrix and thermomechanical stability improve noticeably, with a
maximum storage modulus and the lowest coefficient of thermal expan-
sion value at 50 wt% fiber loading. This suggests that red algae fiber can be
used effectively as a reinforcement for materials, contributing to the devel-
opment of environmentally friendly biocomposites. In a study to improve
the oxidative stability of docosahexaenoic acid (DHA) algae oil, various
antioxidants such as ascorbyl palmitate (AP), vitamin E (VE), phytic acid
(PA), and polyphenols (PH), were combined [17]. The oxidative stability
of DHA algae oil containing 80 mg/kg AP, 80 mg/kg VE, 40 mg/kg PA,
and 80 mg/kg PH was significantly improved. In addition, DHA algae oil
containing the optimal composite antioxidant had a longer shelf life than
the control sample. Chromium oxidation states are considered biologically
and environmentally relevant based on their stability in the presence of
water and oxygen. Chromium-containing compounds are mutagenic and
carcinogenic when inhaled and may be carcinogenic if consumed in large
quantities orally [18]. The high reductive Fe content and specific surface
area of algae-based Fe/C nanocomposite have been shown to have a high
capacity for hexavalent chromium (Cr(VI)) removal [19, 20]. Because of
the stabilizing property of EPS in algae, the use of extracellular polymeric
substances (EPS) has been shown to improve the product composition and
efficiency of Cr(VI) removal. As a result, Cr(VI) was efficiently removed
by an algae-based Fe/C nanocomposite, indicating its potential application
in environmental remediation. Evidence has shown that the development
of synthetic nanoparticles has several hazardous implications. In order to
produce a newer environmentally friendly nanoparticles, the use of green
methods is inevitable. Several novel approaches for nanoparticle synthesis
have been explored using natural resources such as the blue-green algae
[21]. Many of the bionanocomposites produced have several applications
in medicine, catalysis, sensors and bioremediation. Algae with hydroxyl,
amino, and peptide functional groups have also been employed to boost
the adsorption capability of a layered double hydroxyl material. The Cr(VI)
removal effectiveness of these algae-prepared composites was improved,
as well as the stability and reusability over multiple cycles. The creation of
a diatom-FeOx composite has been demonstrated to be a new sorbent for
the removal of arsenic from water [22]. The primary function of diatom
was to immobilize iron-oxide on the composite in order to achieve suc-
cessful bioremediation.
6.4 Techniques and Methods Involved in the

Production of Algae Biocomposites
Natural fiber composites have continued to be in high demand. Natural
fiber composites made from highly marketed fibers like flax, hemp, and
sisal have grown to represent a significant part of polymeric composites.
However, there has been minimal focus on expanding natural fiber com-
posites to accommodate new sources of emerging natural reinforcements,
such as recycled algal fibers, with a number of environmental advantages
[23]. Where traditional mineral and synthetic-based materials can be sub-
stituted with green composite materials, there are tremendous prospects.
It’s crucial to understand green composites’ production procedures and
optimize process parameters before they can be employed to make a vari-
ety of products. Injection molding, extrusion, thermoforming, and com-
pression molding are some of the most prevalent technologies. Cooling
is the most time-consuming part of the injection molding process which
can be improved on by using conformal cooling systems or copper molds
with high thermal conductivity [24]. Conformal cooling channels are often
aligned with the injection-molded product’s geometry, they tend to extract
more heat and remove it more uniformly than traditional cooling systems.
Cooling channels are created by drilling in copper mold inserts, and heat
removal is aided by copper’s high thermal conductivity coefficient, which
is many times that of steel. Designing optimal cooling systems is a dif-
ficult task; proper design necessitates injection molding simulations, but
the accuracy is determined by the precision of the input parameters and
boundary conditions. Extrusion is a process in which a substance is forced
to flow through an aperture or die, resulting in plastic deformation. The
material takes on the die’s cross-sectional profile, and if the material has
the right characteristics, that shape is preserved in the final extrudate [25].
Thermoforming procedure starts with an extruded sheet of plastic. The
procedure entails heating the plastic sheet to a soft or pliable temperature
range. The sheet is then stretched against a single-sided mold that is kept
cool. Compression molding is a technique in which the preheated molding
material is first placed in an open, heated mold cavity. The mold is closed
with a top force or plug member, and pressure is applied to force the mate-
rial into contact with all mold surfaces, while maintaining heat and pres-
sure until the molding material cures [26]. Some of the other methods that
could be employed include melt mixing, solvent casting and hot molding.
6.5 Antiproliferative Activities of Algae

Evidence suggests that marine algae have cytotoxic, antiproliferative, and
apoptotic effects, which help to manage cancer pathologies. Petalonia fas-
cia, Jania longifurca, and Halimeda tuna culture extracts were prepared
to test their effects on the mouse neuroblastoma cell line, NA2B [27, 28].
The survival and proliferation of NA2B cells were assessed using the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay after treatment with algae extracts. The neurotoxicity-screening test
(NST) showed significant neurite inhibition with moderate damage at IC50
dilutions of the extracts, implying that the algae tested may have potential
for use in cancer treatment. The effects of three macroalgae (Ulva reticu-
lata, Sargassum wightii, Gracilaria sp.) were determined against cervical
carcinoma cells using MTT bioassay method. At concentrations of 1–50
M, the extracts of U. reticulata exhibited antimicrobial activity against
Pseudomonas aeruginosa (6.00 mm) and potential antiproliferative activity
against HeLa cells (IC50 37 mol/L) [28]. Consumption of marine algae has
been linked to a lower incidence of cancer in countries that traditionally
consume marine products. The effects of water-soluble sulfated polysac-
charides (hydrocolloids) isolated from the red seaweed Laurencia papillosa
on the human breast cancer cell line MCF-7 were investigated in a study
[29]. For cells exposed to the polysaccharides for 24 hours, the results
showed a significant inhibition of MCF-7 cell viability in a dose-dependent
manner. This indicates that L. papillosa SPs could be a promising candidate
for breast cancer prevention and treatment.
6.6 Anti-Inflammatory Activities of Algae

Many physiological and pathological processes are characterized by infla
mmation. The pathological aspects of many types of inflammation, in con-
trast to the physiological processes, are well documented. Infection and
tissue injury are the most common causes of inflammation. These are both
adverse conditions that trigger inflammation and cause the recruitment of
leukocytes and plasma proteins to the affected tissue site [30]. Tissue stress
also causes an adaptive response known as para-inflammation, which
responds to tissue-macrophages and is an intermediate between a basal
homeostatic state and a classic inflammatory response. Para-inflammation
may be responsible for the chronic inflammatory conditions that are often
associated with human diseases [31]. Neuroinflammation plays a role in
the development and progression of neurodegenerative diseases such as
Alzheimer’s and Parkinson’s. Natural anti-inflammatory compounds, such
as algae, are promising candidates for developing effective therapeutic
strategies. These algae contain antioxidants, proteins, vitamins, minerals,
soluble dietary fibers, polyunsaturated fatty acids, polysaccharides, ste-
rols, carotenoids, tocopherols, terpenes, phycobilins, phycocolloids, and
phycocyanins. In a study involving a high-fat diet-induced obese mouse
model and bone marrow-derived macrophages, researchers looked into
the potential anti-obesity and anti-inflammatory effects of four types of
domestic brown seaweeds (BMDM) [32]. For 16 weeks, male C57BL/6N
mice were fed a low-fat diet (LFD), a high-fat diet (HFD), or an HFD con-
taining Undaria pinnatifida, Laminaria japonica (LJ), Sargassum fulvellum,
or Hizikia fusiformis (HF). When BMDM from mice fed HFDs with sea-
weeds were compared to BMDM from mice fed HFDs with LPS stimu-
lation, they showed differential regulation of pro-inflammatory cytokines
such as IL-1 and IL-6. Although seaweed consumption did not prevent
long-term HFD-induced obesity in C57BL/6N mice, it did reduce insu-
lin resistance (IR) and pro-inflammatory cytokine circulation. Brown
seaweeds Laminaria japonica (LJ) and Hizikia fusiformis (HF) are known
to have a variety of health-promoting properties. A study was conducted
using both in-vitro and in-vivo models to investigate the anti-inflammatory
activities of LJ and HF [33]. In vitro, C2C12 myotubes, mouse-derived
skeletal muscle cells, were treated with LF or HF extracts, and in vivo, mus-
cle tissues from C57BL/6N mice fed a high-fat diet supplemented with 5%
LF or HF for 16 weeks were used. LJ and HF induced phosphorylation of
protein kinase B and AMP-activated protein kinase in both in-vivo and
in-vitro skeletal muscle models. In lipopolysaccharide-stimulated C2C12
myotubes, LJ and HF significantly decreased tumor necrosis factor-alpha;
whereas both extracts increased interleukin (IL)-6 and (IL)-10 production,
which suggests that they could be useful therapeutic agents for reducing
associated inflammation. Ephedra nebrodensis (Ephedraceae) is a plant
with numerous biological functions. In traditional medicine, it is used to
treat respiratory problems and hepatic pathologies. In a study in mice, the
anti-inflammatory properties of two hydro-alcoholic extracts of E. nebro-
densis were evaluated in vitro and in vivo [34]. The anti-inflammatory
activity of the extracts was determined in vitro and in vivo using bovine
serum albumin denaturation and croton oil-induced ear edema, respec-
tively. In vivo, the extracts have strong anti-inflammatory effects and
reduce ear edema by 70.37% ± 2.00% and 72.22% ± 1.94%. This validates
the herb’s traditional use in the treatment of various diseases.
6.7 Potential Health Benefits of Algae Biocomposites

Macroalgae are a large type of photosynthetic algae that live in the ocean’s
intertidal zone. Recent research suggests that glycans generated from mac-
roalgae have a lot of potential for keeping the gut microbiome and immune
system healthy [35]. The human gut bacteria have developed unique arse-
nals for utilizing a wide range of macroalgal glycans and producing a wide
range of oligosaccharides. These oligosaccharides interact with immune
cell receptors and are also available for microbial fermentation, allowing
them to play an important role in gut homeostasis. The demand for marine
and freshwater algae and related products is growing over the world. Algae
may become one of the most important foods for nutritional purposes in
the near future. They include high-quality protein and other bioactive com-
pounds that could help with obesity and diabetes management. Algae con-
tain fiber, polyphenols, ω-3 PUFAs, and bioactive molecules with potential
antidiabetic activity. Carbohydrate digestion and absorption, blood glu-
cose, gastrointestinal neurohormone secretion, glycosylation products,
and insulin resistance have all been shown to be influenced by whole algae,
algal extracts, or its isolated compounds [36]. Seaweeds, for example, have
recently been discovered to be potential sources of beneficial metabolites
and bioactive components with a variety of physiological actions. Seaweed
polysaccharides, for example, have been shown to have anticoagulant,
anti-inflammatory, antioxidant, anticarcinogenic, and antiviral proper-
ties [37]. Sulfated polysaccharides, which interact with surfaces and cel-
lular proteins, are abundant in seaweeds and contribute to the majority of
their biological action. Consumption of seaweeds may be considered as a
means to boost immunological responses, according to several toxicolog-
ical assessments and clinical trials. Polysaccharides from marine microal-
gae and seaweeds have been demonstrated to have immunomodulatory
activities in humans and animals [38]. As a result, these polysaccharides
can act as immunosuppressive molecules in the treatment of inflammatory
disorders like autoimmune diseases and sepsis, as well as inducing immu-
nological responses to cancer and other infectious diseases. Marine algae
have recently been incorporated into synthetic polymers, which is being
investigated as an alternate approach for manufacturing grafts because they

are a plentiful and inexpensive supply of biopolymers. As an alternative to
porcine-derived membranes, a unique composite patch was developed by
combining Sargassum vulgare powders (SVP) with polylactide (PLA) [39].
A modified solvent casting process was used to create SVP-PLA compos-
ite patches. Human osteoblasts (HOBs) and osteosarcoma cells (SaOS-2)
were planted on tidy PLA and SVP-PLA patches after extensive material
characterization to test cytocompatibility. HOBs cultivated on SVP-PLA
composite had stronger cytocompatibility and proliferation than those cul-
tured on clean PLA, according to MTT and BrdU tests. Cell proliferation
was significantly reduced in SaOS-2 cells grown on SVP-PLA. These com-
posite patches have an antiproliferative effect on SaOS-2 cells while having
minimal influence on HOB adhesion or proliferation.
6.8 Challenges and Issues Related to Algae

Biocomposites Use
Researchers are interested in using algae-based biopolymers as one of the
alternative options to create a sustainable circular economy around the
world. Microalgae biopolymer has several advantages over other feed-
stocks, including its autotrophic complex, which reduces greenhouse gas
emissions, quick growth ability with flexibility in a variety of settings, and
the capacity to compost, which provides greenhouse gas credits [40]. The
challenges faced in the circular economy, issues regarding the scale-up and
operational cost of microalgae production, and the life cycle assessment of
algal-based biopolymer are all part of the algae bioeconomy’s future pros-
pects and challenges [41].
6.9 Conclusion
Algae have been shown to have several biological activities, some of which
include immunomodulatory, antitumor, antiviral, antioxidant, and hypo-
lipidemic activities. Their anti-inflammatory and antiproliferative potential
have made them useful in the protection against cancer cells. In addition,
they offer a wide range of health benefits, which makes them a vital biore-
source. These algae have important applications in producing biopolymers
which have a variety of applications such as environmental remediation,
adsorbents, and antioxidants [42–50]. Although there are conventional
methods of manufacturing these algae-biopolymers, efforts are ongoing

to develop novel approaches to improve the yield and efficiency of these
biopolymers.
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7
Natural Compounds of Algae Origin with
Potential Anticarcinogenic Benefits
Adewale Omowumi Oyeronke1*, Asowata-Ayodele Abiola Mojisola2†,
Akomolafe Seun Funmilola3† and Adetunji Juliana Bunmi1†
Department of Biochemistry, Faculty of Basic and Applied Sciences,

1
Osun State University, Osogbo, Osun State, Nigeria

2
Department of Biological Sciences, Faculty of Science, University of Medical
Sciences, Ondo, Ondo State, Nigeria
3
Department of Biochemistry, Faculty of Science, Ekiti State University, Ado Ekiti,
Ekiti State Nigeria
Abstract
Cancer continues to be a menace to public health, with the increasing rise in
cancer cases demanding effective therapies with minimal side effects. Generally,
typical treatment of various diseases started shifting towards natural products,
especially those of plant origin, several years back. The reason is not unrelated to
the fact that various conventional anticancer drugs, for example, kill rapidly divid-
ing cells otherwise regarded as cancer cells but the normal cells are also affected,
which eventually leads to the frequently reported side effects. Of the various plants
that have been utilized in treatment of numerous diseases, algae happen to be
the most underexplored for various medicinal properties. Recently, various bio-
active components have been isolated from different algae, especially microalgae,
for treatment of various diseases, including viral infections, diabetes, asthma,
inflammation and cancer to mention a few. Their anticarcinogenic properties are
the most striking features of these bioactive components found in microalgae.
This chapter focuses on natural compounds isolated from microalgae which are
engaged in the management of different cancers and also discusses the reported
principles of antiproliferative properties of these compounds.

†
These authors have the same contribution to this work.
153
Keywords: Microalgae, natural products, antioxidants, anticancer therapy,

oxidative stress, inflammation, proliferation, DNA mutation
7.1 Introduction
Algae are defined as an enormous, diverse group of photosynthetic
organisms that are not fundamentally strictly associated, but belonging
to varying evolutionary ancestors. They vary from unicellular microal-
gae, which include Chlorella and Diatoms, to multicellular types, includ-
ing giant kelp, which is enormous brown alga that can reach 50 m length.
Algae are mostly marine and autotrophic, and lack many of the distinct
cell and tissue types, such as stomata, xylem, and phloem, the features
which distinguish plants on the land [1]. Algae have ability to grow in
isolation or alongside other organisms, and can withstand a wide array of
contrary environmental conditions [2]. Algae could be categorized in two
ways: i) based on colors, they can be categorized mainly into green algae
(Chlorophyta), red algae (Rhodophyta) and brown algae (Phaeophyta);
and ii) based on size, they can be classified into macroalgae or microal-
gae. Macroalgae are large-sized multicellular algae known as seaweeds
and are evident to the bare eye, whereas microalgae are single-celled
microscopic algae, that can be either prokaryotic or eukaryotic [3].
Algae are special plants which are endowed with great varieties of
medicinal properties as a result of the general byproducts derived from
them. These byproducts have been reported to take care of many diseases
due to their medicinal effects, including anticoagulation [4], antiasthmatic
and anti-inflammatory activities [5], antidiabetic and antioxidant activi-
ties, antiviral activity [6], antiallergic activity [7], and anticancer activity
to mention a few.
Of the several diseases reported globally, cancer happens to be the most
common and serious one. Reports have it as the leading cause of death
which overwhelms the public [8]. It is established that one in every six
deaths are caused by cancer [3]. Death by cancer is increasing yearly with
the largest proportion being recorded in the low-income population [9].
Over 200 different types of cancer exist [8] that affect different parts of the
human body. The European Cancer Observatory reported the estimates
of four types of cancer that are most common in the European Union in
2012: colon cancer cases were 342,137, lung cancer (plus trachea with
bronchus cancer) cases were 309,589, breast cancer cases were 358,967 and
there were 82,075 cases of skin melanoma [10]. Some of these cancers have
Anticarcinogenic Compounds of Algae Origin 155
been discovered to eventually spread into other tissues through metastasis,

which is usually deadly [8].
As a result of this great threat, significant consideration has been given
toward elimination of cancer [11]. The first line of treatment to cure can-
cers has usually been chemotherapy, which encompasses utilization of
chemicals to constrain the growth or damage of cancerous cells [3]. While
several chemotherapeutic drugs can succeed in expanding the survival
time of patients, there are extensive side effects associated with them and
these frequently compromise the value of the lives of affected patients.
These side effects include vomiting, canker sores, baldness, nausea, diar-
rhea, loss of appetite and fatigue. Therefore, new anticancer agents are con-
stantly searched for from various resources. Exploration of natural agents
for their active anticancer components with minimal side effects has pro-
vided an impressive strategy for anticancer drug development [9]. Almost
60% of the drugs utilized in medical research, including oncology, have
been reported to have their foundation from natural bases, and about a
third of those frequently traded are either natural compounds or products
obtained from them. In recent times, there has been increased interest in
marine bioprospecting; and effective natural products, including terpenes,
steroids, alkaloids, polyketides, etc., are now being assessed from marine
sources. Presently, there are four anticancer agents obtained from seven
marine-derived drugs available on the market [8]. Moreover, 23 out of
close to 26 marine natural yields available in clinical trials are anticancer
agents [12]. Of all the aquatic organisms, algae have recently been explored
for various medicinal activities, especially anticarcinogenic activities. A
lot of natural antitumor combinations have been generally reported to
be produced by algae, which have now made them important targets in
cancer therapy in the last few decades [9]. The type of algae that is more
commonly reported for high anticarcinogenic constituents are microalgae.
Phytochemicals derived from microalgae have been reported to possess
additional prospective biological properties compared with the terrestrial
source (plant phytochemicals) [13, 14].
Microalgae contain a collection of phenolic compounds which are dis-
covered to be quite distinct compared to numerous plant classes, including
fruits, vegetables and pharmaceutical plants [15]. These unique constitu-
ents have actually been earlier reported for their anticarcinogenic activ-
ities which could at least in part justify the anticarcinogenic effects of
microalgae.
The mechanism through which microalgae elicit their effects of anti-
carcinogenic activity is multifaceted due to the fact that their substantial
mechanical multiplicity involves various connections. Microalgae act as
an excellent source of numerous beneficial derivatives, including carbon

compounds, which have application in medical, cosmetics, and pharma-
ceuticals industries [16]. Additionally, many other components which
exist in microalgae, including proteins, lipids, antioxidants, vitamins and
polysaccharides [9], perform diverse beneficial roles in living systems.
Microalgae also increase natural killer-cell activity, thereby improving
the host’s defense system, and enhance stimulation of the immune sys-
tem, which prevents growth of cancer cell [3]. Consequently, it is being
postulated that microalgae will be a significant causative feature in the
establishment of anticancer therapy. This chapter briefly discusses cancer
progression, predisposing factors and treatment. It also discusses fea-
tures of microalgae as new sources of products for cancer treatment and
attempts to elucidate different microalgae-derived natural products with
anticancer activities and various cancers that can be treated by them. In
addition, possible mechanisms for the activities of these products are
discussed.
7.2 Progression, Predisposing Factors and Treatment

of Cancer
7.2.1 Cancer Progression
Cancer happens to be the most common serious disease with a higher
mortality rate than malaria, HIV/AIDS, and tuberculosis combined [17].
Overall, cancer grew from 7.56 million of global deaths reported in 2008 to
10.21 million deaths in 2020 [18]. Developing countries had more cancer
cases compared to developed countries [19]. Development of cancer by a
normal cell have been linked to certain characteristics, including resistance
to the signals which control cell proliferation, resistance to apoptosis, abil-
ity to avoid replicative senescence and evade differentiation thereby over-
coming the limitations on proliferation, genetic instability, ability to invade
surrounding tissues and ability to metastasize [20, 21]. During develop-
ment of cancer, cancer cells overcome irreversible arrest of cell prolifer-
ation and altered cell function, which is replicative cell senescence, and
become “immortalized,” which implies continuous and indefinite cell divi-
sion [22]. Development of cancer takes many years to occur and comprise
numerous advancements. The initial abnormal cell first undergoes certain
modifications that allow it to propagate considerably more rapidly than
normal cells in similar tissue; this ability is then transmitted to succeeding
newer cells [19, 20, 23].
7.2.2 Predisposing Factors to Cancer

The vast majority of cancers occur by chance as a result of genetic muta-
tions in the genomes of cancer cells which can occur as a consequence of
inheritance and metabolic reactions. Other predisposing factors include
cigarette smoking, radiation, diet, environmental pollutants, alcohol, oxi-
dative stress, obesity and physical inactivity and infectious organisms such
as viruses. These factors might act sequentially or in combination to initi-
ate or activate cancer cells [20, 23, 19].
7.2.3 Treatment of Cancer

There are several treatment strategies for cancer, including radiation ther-
apy, surgery, targeted therapy, chemotherapy, hormone therapy, stem cell
transplant, immunotherapy, precision therapy, etc. Although these treat-
ment strategies can extend the lives of patients, the significant side effects
associated with them are numerous and there is usually a trade-off with
the quality of life of the affected individual [3]. Therefore, looking for more
alternative approaches to cure cancer with minimal or no side effects con-
tinues to be of great importance for establishing novel agents for cancer
therapy in the continuing war against this menacing disease [8].
The substantial number of numerous drugs of natural origin used in the
management of diseases, especially cancer, testify to the benefits derived
from marine organisms, especially algae. The type of algae that is more
commonly reported for high anticarcinogenic constituents are microalgae,
which contain a collection of phenolic compounds that are discovered to
be quite distinct compared to many other plant species [15]. Microalgae
are now being explored for their various natural compounds with anticar-
cinogenic properties.
7.3 Features of Microalgae

Microalgae are known to be photosynthetic and microscopic organisms,
that form the main component of phytoplankton in fresh and marine
water. They have the capacity to acclimatize to extremely adverse condi-
tions from mild to very harsh environments, including icy environments
and hydrothermal outlets [3]. They contribute approximately 40% of global
output [24]. They have short generation times and have populated nearly
all biotopes [25, 26]. Microalgae may be simply cultured in photobioreac-
tors (such as 100,000 L biodigesters) to acquire a large organic matter and
signify a renovatable reserve for drug detection. They utilize energy from
sun and carbon fixation, thereby moderating greenhouse gas properties
with the elimination of byproducts from phosphorous and nitrogen, which
may constitute pollution as determined by their quantities [27]. Microalgae
are useful in aquatic drug detection due to their anabolic plasticity and
this can activate the generation of numerous products with potential uses
in different biotechnology sectors, including health, energy, food, bioma-
terials and environment [25, 26]. Currently, research on the therapeutic
effects of microalgae has increased due to the efficacy of their intrinsic
active constituents against a number of pathogens [28–30]. Microalgae are
mostly composed of various amounts of lipids, carbohydrates, proteins,
and nucleic acids; the level of these compounds may differ depending on
vitamin, mineral, and polysaccharide constituents [8].
7.4 Sources of Microalgae

Microalgae are large clusters of autotrophic phytoplankton that can be cat-
egorized according to the source from which they are obtained as either
freshwater microalgae or maritime microalgae.
Freshwater microalgae are those found in freshwater environments;
they can be separated microscopically and majorly into 10 phyla [3].
Additionally, there are negligible phyla, which have minimal effect on
freshwater milieu, namely Haptophyta (five species), Prasinophyta (13
species), Eustigmatophyta (three species), Raphidophyta and Glaucophyta
(two species each) have also been reported [31]. Maritime microalgae are
regarded as an example of the significant primary bases for the newly dis-
covered beneficial genes and metabolites.
7.5 Fractions of Microalgae Species with Anticancer

Properties
As of now, over 30,000 deep-rooted microalgae species exist. Fractions of sev-
eral of these species were recounted for their capacity to prompt cell growth
arrest in various cancer cell lines, thereby eliciting anticarcinogenicity.
7.5.1 Carotenoid-Rich Extracts of Chlorella Species

Carotenoid-rich extracts of Chlorella species, including C. ellipsoidea
and C. vulgaris, were assessed for their antiproliferative abilities against
a human colon carcinoma cell line (HCT116). The species generally are
known to be a rich salable basis of carotenoids such as lutein, astaxan-
thin, zeaxanthin and β-carotene. The result of this study showed anti-
proliferation and pro-apoptotic abilities of the two Chlorella species
[32].
7.5.2 Chaetoceros Calcitrans Ethyl Acetate

and Ethanol Extracts
Nigjeh et al. and Goh et al. worked on ethanol extract and ethyl ace-
tate extract respectively from Chaetoceros calcitrans (the planktonic dia-
tom). They used various breast cancer cell models, including MCF-7;
MDA-MB-231 (adenocarcinoma); MCF-10A (breast epithelial cancer
cells); and mouse breast carcinoma (4T1). They also used peripheral
blood mononuclear cells (PMBC), cervix epithelial carcinoma (HeLa),
liver HCC (HepG2), human lung adenocarcinoma (A549), human pros-
tate carcinoma (PC-3), human ovarian adenocarcinoma (Caov3) and
human colon adenocarcinoma (HT-29). Nigjeh et al. observed interest-
ing antiproliferative outcome of Chaetoceros calcitrans ethanol extract
which was comparable to tamoxifen and also observed a significant rise
in the Bax, with the caspases 3 and 7 transcripts which are proapoptotic
protein. Goh et al., who tested some other extracts (like hexane, dichloro-
methane and methanol), found C. calcitrans crude ethyl acetate extract to
have cytotoxic properties against the MDA-MB-231 cancer cell line. The
lethal effect was found to be precise against cancer cells as an assessment
on fibroblasts, which are nontumorigenic cell line and showed no cyto-
toxic ability [33–35].
7.5.3 Amphidinium Carterae Organic Fractions
Samarakoon et al. confirmed several portions from the dinoflagellate

Amphidinium carterae extract to have antiproliferative efficacy in cells such
as HL-60 (human promyelocytic leukemia cells), B16F10 (mouse mela-
noma tumor cells), with A549 (adenocarcinomic human alveolar basal
epithelial cells). The authors also used a mouse monocyte macrophage cell
line to perform cytotoxicity tests (RAW 264.7). The chloroform fraction of
A. carterae had the strongest activity and caused a considerable decrease in
the HL-60 cells viability [33].
7.5.4 Methanolic Extracts from Amphidinium carterae,

Prorocentrum rhathymum, Symbiodinium sp., Coolia
malayensis, Ostreopsis ovata, Amphidinium operculatum,
and Heterocapsa psammophila
Eleven different benthic dinoflagellate strains (Prorocentrum rhathymum,
Coolia malayensis strain 1, Amphidinium carterae, Symbiodinium sp.,
Ostreopsis ovata strain 1, Amphidinium operculatum strain 1, Ostreopsis
ovata strain 2, Coolia malayensis strain 2, Coolia malayensis strain 3,
Heterocapsa psammophila and Amphidinium operculatum strain 2) were
obtained from Jeju Island off the coast of Korea in 2011, and then cultured
to monitor RAW264.7 and HL-60 cells. In the study, Ostreopsis ovata 1 and
Amphidinium operculatum 1 were the only extracts found to hinder the
growth of HL-60 cells significantly [36].
7.5.5 Skeletonema marinoi Hydrophobic Fraction

Lauritano et al. studied the role of several species of microalgae (32 in
number) obtained with water-acetone (1:1) mixture and additionally sepa-
rated with Amberlite RXAD16N resin using acetone as the resin eluent to
attain a non-polar fraction. The results showed that the non-polar portions
from Skeletonema marinoi, Alexandrium minutum, Alexandrium tamutum
and Alexandrium andersoni repressed the progression of melanoma cell
line (A2058) significantly. Further study showed that Alexandrium spe-
cies were lethal on a normal lung fibroblast (MRC-5) cell line. Strains of
Skeletonema marinoi (FE6 and FE60 strains from the Adriatic Sea) were
verified on an A2058 cell line, assay was carried out in normal and cancer
cells to check cytotoxicity. The outcome revealed that the FE60 strain was
the only one active against A2058 and this occurred solely after cultured in
nitrogen-starvation conditions [25].
7.5.6 Canadian Marine Microalgal Pool Aqueous Extract

Antiproliferative and anti-colony-forming activities of a fresh aquatic
microalgal material (dried powder) from Canada was investigated on pro-
liferation of different cancer cells, virtually all of which were significantly
repressed at a measure of 5 mg/mL. The anti-colony activity of the extract
revealed successful inhibition of colony creating capacity of all the tested
cancer cells tested with the extract at the most minimal measure (0.5 mg/
mL) tested [37].
7.5.7 Chlorella sorokiniana Aqueous Extract

In many countries, Chlorella sp. biomass, which is mainly produced in Asia,
is listed among the widely used dietary supplements. A study on the role of
diatom Chlorella sorokiniana (marine strain) extracted with hot water, was
carried out on lung adenocarcinoma cell lines (A549 and CL1-5). Results
of cell viability revealed a dose-related suppression on the two cell lines
tested. The authors also verified the principle of function of C. sorokini-
ana extract by employing analysis by flow cytometry to ascertain a proba-
ble process of cell apoptotic/cycle arrest. It was found that cell cycle arrest
was not involved during the period of the study but a significant upsurge
in population of sub-G1 phase was detected, an indication of significant
apoptosis. Protein expression of different types of caspase-9, caspase-3 and
poly (ADP-ribose) polymerase (PARP) was elevated from the two cell lines
beyond 24 hours introduction to the extract of microalgal. Caspases 3 and
9 activation indicated mitochondrial pathway as the main apoptotic path-
way involved. Furthermore, the ratio of Bax/Bcl-2 was elevated beyond 24
hours of exposure, confirming increased apoptosis [38].
7.6 Compounds with Anticarcinogenic Activities

Isolated from Marine Microalgae
In the last section outstanding and exciting anticarcinogenic activities were
displayed by various fractions obtained from several species of microalgae.
However, the activities of these fraction character may not be unrelated to
their constituent bioactive molecules. Active compounds with anticancer
capabilities are one main group of highlighted compounds from microal-
gae; therefore, some of the natural bioactive compounds with anticancer
activities extracted from microalgae are discussed below.
7.6.1 Polysaccharides
Polysaccharides are complex carbohydrate structures which are made
from several monosaccharide molecules joined by diverse glucosidic link-
ages [39]. Polysaccharides are organic bioactive compounds possessed by
plants but they generally appear in microalgae and also in animals, micro-
organisms and other different plants [40, 41]. Unique functional properties
of polysaccharides have been linked to their structure organized by the
building blocks [70].
Polysaccharides obtained from Spirulina species and Ecklonia cava were

asserted to enhance excision, unscheduled DNA synthesis, radiation-dam-
aged DNA repair activity and also significantly exhibited enhanced activ-
ity of endonuclease, DNA production of sarcoma 180, ascetic hepatoma
cells, and inhibited propagation of ascitic hepatoma cells of mice [42, 43].
Polysaccharide from Spirulina platensis prevented tumor attack and spread
[44]. It was detected that the mechanism of anticarcinogenic ability of this
acidic polysaccharides in S. platensis included tumoricidal property asso-
ciated with macrophage-tumor necrosis factor (TNF). It was also found
that polysaccharides from Spirulina reduced growth of glioma cell (murine
RSV-M) past partial modulation of interleukin-17 generation and sup-
pression of angiogenesis [45]. Polysaccharides which were extracted from
Japanese kelp, such as Hijikia fusiforme, Undaria pinnatifida, Laminaria
japonica and Eisenia bicyclis, have been documented as future antigeno-
toxic compounds [46]. Fucoidans (Figure 7.1) (sulfated polysaccharides
rich in fucose obtained mostly in brown seaweeds) were reported for their
antiproliferative activities in Lewis lung adenocarcinoma affected mice
through a yet unknown mechanism [47]. Anticancer activity of these sub-
stances on human HS-Sultan cells also included ERK and caspase path-
ways [48]. Fucoidans are also reported to enhance immunomodulatory
capacity that confines tumor cells diffusion and growth by facilitating the
damage of the tumors past responses of NK cell and type 1 T helper (Th1)
cells [49]. This polysaccharide consists of fucose and a few galactose units.
The anticancer activities of fucoidans were confirmed to be associated with
their molar masses and sulfate contents. It is documented that the antican-
cer ability of fucoidans is increased when they are hydrolyzed under gen-
tle conditions [50]. Fucoidans are confirmed to enhance Smac/Diablo and
cytochrome c discharge by mitochondria as well as enhance mitochondrial
membrane permeability [51].
H3C
HO
O H3C
-O SO
3
O
OSO3-
O
OSO3-
Figure 7.1 The structure of Fucoidan.

7.6.2 Phycocyanin
Phycocyanin is a pigment-protein complex from the light-harvesting phy-
cobiliprotein family, along with phycoerythrin and allophycocyanin [52].
It is consistently used as a color-enhancing agent in dairy and dietary prod-
ucts, including beverages, candies, gums, jellies; and also in maquillages,
including eyeliners, eye shadows and lipsticks in Japan and China [53].
Phycocyanin (Figure 7.2) isolated from algae has been reported for its anti-
carcinogenic activities against different types of cancers [54]. The phyco-
cyanin isolated from S. platensis is said to possess radical scavenging and
antioxidant properties and exhibits anticancer activity against squamous
cell carcinoma. It exhibits inflammatory and anticancer properties and also
prompts in-vitro apoptosis in HeLa cells by stimulating cell death enzymes,
caspases 2, 3, 4, 6, 8, 9, and caspase 10 [55]. The selenium-enriched phy-
cocyanin isolated from Spirulina platensis also showed strong anticarcino-
genic properties against MCF-7 and A375 cancer cells where it stimulated
apoptosis via nuclear compression and buildup of sub-G1 cells and DNA
disintegration in both cells [56]. Phycocyanin also improves immune
response by stimulating function of macrophage, interleukin-I assembly
and phagocytosis. This ability is what contributes to its importance in
treatment and prevention of all types of cancers [57].
COOH COOH
H 3C H3C
H3C CH3 H3C

H3C
O N O
N N N
H H H
Figure 7.2 The structure of phycocyanin.
7.6.3 Chlorophyll
Chlorophyll and related compounds like carotene and lutein isolated
from different strains of algae have accounted for antiproliferative bioac-
tivity both in vitro and in vivo. Tumor preventive impacts of chlorophyll
(Figure 7.3) with subordinates is widely focused on, particularly their in-
vitro anticarcinogenic impact on several ecological and dietary mutagens.
Chlorophyll-a and chlorophyllin have displayed huge importance in the
O
H CH3
H3C
N N CH3
MGII
N N
H3C CH3
CH3 CH3 CH3

O O
H3C O O OCH3
2
Figure 7.3 The structure of chlorophyll.
instigation of ornithine decarboxylase in fibroblasts on mouse skin created

via a tumor enhancer with in-vitro cell culture tests [26, 58].
7.6.4 Polyunsaturated Aldehydes (PUAs)

Three polyunsaturated aldehydes were isolated in the aquatic diatoms
Thalassiosira rotula, S. costatum and P. delicatissima. These compounds,
2-trans-4-trans-7-cis-decatrienal, 2-trans-4-cis-7-cisdecatrienal and 2-trans-
4-trans-decadienal (Figure 7.4), were found to have anticarcinogenic activity
on the human colon adenocarcinoma (Caco-2) cell line [59] and on A549 and
COLO 205 [60]. They showed anticarcinogenicity through apoptosis and were
found to be nontoxic in normal cell lines.
CHO
CHO CHO
2E,4Z,7E-decatrienal 2E,4E,7Z-decatrienal 2E,4E-decadienal

CHO CHO CHO
2E,4Z-octadienal 2E,4Z,7-octatrienal 2E,4Z-heptatrienal
Figure 7.4 The structure of polyunsaturated aldehydes.
7.6.5 Violaxanthin
Anticancer monitoring of the extracts obtained in Dunaliella tertiolecta
was performed in diverse lines of cancer cells: MDA-MB-231, A549,
MCF-7 and LNCaP. The extracts preparation was by several solvents with
H 3C OH
H3C CH3 CH3 CH3
O
O
CH3 CH3 H3C CH3
HO CH3
Figure 7.5 The structure of violaxanthin.
different polarities; these include ultrapure water, ethanol and dichloro-

methane. Dichloromethane extract was the only one that revealed remark-
able action on MCF-7 cells. A subfraction of this extract was then made
using RP-HPLC examination and separation, the subfraction was later rec-
ognized to be violaxanthin (Figure 7.5) with 95% purity. Further analysis
with violaxanthin indicated early apoptosis. Cytotoxicity tests are yet to be
achieved in regular human cell lines [61].
7.6.6 Eicosapentaenoic Acid (EPA)

Marine diatom Cocconeis scutellum extracts were screened on MB-MDA468,
BT20, COR, LNCaP, JVM2 and BRG-M [62]. The results, though not
entirely published, showed extract from C. scutellum had extra activity on
BT20. The fractionation of the most active cell line (diethyl ether extract)
from C. scutellum formed three portions having different capabilities. Out
of the three portions, only one significantly reduced the viability of the
treated cell line. Fragmentation of DNA was further determined on this
portion. Results of its composition indicated 4-methylcholesterol (2.3%)
and fatty acids (81.7%). It was eventually decided that the activity of this
OH
Figure 7.6 The structure of Eicosapentaenoic Acid (EPA).

portion was specifically due to its fatty acid subfractions, these fatty acids
were identified to be eicosapentaenoic acid (EPA, Figure 7.6) [62]. This is
because EPA was the only compound in the fraction that was established for
its ability to stimulate apoptosis [63]. The fraction also activated caspases
3 and 8 by Western blot analysis. It has not been established whether EPA
is the individual influence associated with death of BT20 cells or if cordial
relationship exists among different compounds within the same portion
[62].
7.6.7 Stigmasterol
Stigmasterol (Figure 7.7) is one of the major sterols in plasma membranes
of plant cells, and plays a major role in sustaining the structure and physi-
ology of cell membranes [64].
Stigmasterol was isolated from Navicula incerta extracts via chromato-
graphic techniques [65]. The antiproliferative role of this compound was
assessed on HepG2. A dose-dependent trend was observed in the cytotox-
icity induced by this compound on HepG2 cells, though this has not been
confirmed on normal human cells. Another compound, having structures
like phytosterol and double bonds between C-5 and C-22 positions, which
is also found in stigmasterol, was confirmed to induce apoptosis [66].
Generally, all results of the assays carried out specified that stigmasterol
has an enormous apoptotic induction ability, which is probably through
mitochondrial intrinsic apoptotic signaling pathway [8].
H
H
H H
HO
Figure 7.7 The structure of stigmasterol.
7.6.8 Fucoxanthin
Fucoxanthin (Figure 7.8), a xanthophyll having molecular formula C₄₂H₅₈O₆,
is established as an accessory pigment in aquatic micro- and macroalgae.
Fucoxanthin is one of the most observed substances in these organisms, and
is a key carotenoid from brown algae [67]. The fucoxanthin lethality was
C
O O
O
HO
O
HO
Figure 7.8 The structure of fucoxanthin.
evaluated in rats but no obvious toxicity was shown within the 28-day period;
therefore, it is considered as a safe pharmaceutical ingredient. Fucoxanthin
exhibited a solid anticarcinogenic role in HL-60 cells and apoptotic induc-
tion in these cells. Cell viability of this compound was also assessed in cell
lines of colon cancer, including DLD-1, Caco-2, and HT-29, and fucoxanthin
produced significant reduction in tested cell lines viability; however, there is
no report on normal human cells [68]. It is also established that fucoxanthin
is part of the best active antiproliferative compounds among the 15 types of
carotenoids tested.
7.6.9 Nonyl 8-Acetoxy-6-Methyloctanoate (NAMO)

The anticarcinogenicity of NAMO (Figure 7.9) isolated in Phaeodactylum
tricornutum was tested on some cell lines: HL-60, A549 and B16F10 [33].
In this study, NAMO was reported to be solely active on HL-60 cells at the
doses tested. These authors did not test the toxic action of this compound
on normal human cells. Mechanism of action of NAMO was reported to
include induction of DNA lesion and enhanced apoptotic body devel-
opment. Arrest of cell cycle and sub-G1 phase cell compilation was also
detected to arise with NAMO in a dose-related way [8]. Regression of
Bcl-x, an anti-apoptotic, activation of Bax, a pro-apoptotic protein, and an
enhancement in the appearance of p53 proteins and caspase-3 were also
reported to complement the mechanism of action of NAMO [8, 33].
OH
O
O
HO
Figure 7.9 The structure of nonyl 8-acetoxy-6-methyloctanoate.

7.6.10 Monogalactosyl Glycerols

Monogalactosyl glycerols (Figure 7.10) are forms of glycerol isolated from
Phaeodactylum tricornutum. Two different monogalactosyl glycerols were iso-
lated from diatom Phaeodactylum tricornutum in the genus Phaeodactylum
[69]. These authors tested the isolated monogalactosyl glycerols on W2 and
D3 (immortal mouse epithelial cells). W2 is a wild-type cell line, whereas, the
apoptotic ability has been inactivated via gene manipulation in D3 cells. In
the present study, the monogalactosyl glycerols significantly induced apopto-
sis in the wild-type cell as the treatment enhanced cell death rate, while in the
D3 cells, since the gene responsible for apoptotic function has been deleted in
these cells, the growth rate increased significantly. The results proved that the
isolated compounds induced apoptosis in the W2 cell line [69].
O
OH
HO O
O O
HO O
OH O
Figure 7.10 The structure of monogalactosyl glycerols.
7.6.11 Other Active Compounds from Microalgae

with Anticarcinogenic Activities
There are other active compounds isolated from microalgae which show
significant anticarcinogenic capacities, including pheophytin [70, 71], carot-
enoids, siphonaxanthin [68, 72], stypodiol diacetate [73], glycoprotein [73,
74], meroditerpenoids [75], stypotriol triacetate [76], yessotoxins [77], elatol
[78], cannabinoids [79], and monoterpenes [80], both in vitro and in vivo.
7.7 Conclusion and Recommendation

Plants remain an important part of health maintenance. Traditional plant-
based remedies are still very important to people in impoverished nations,
and they are also leading to the development of new medication candidates.
However, scientific testing of therapeutic herbs is required to justify their
usage. The high mortality rate among cancer patients continues to indi-
cate the present low efficacy of medicines in cancer treatment. Substances
formed chemically continued to be the focus of cancer research for many
years. Natural products or a combination of diverse phytochemicals have

only begun being studied for cancer treatment in the last few decades.
This chapter emphasized the promising and effective function of regu-
lar algae-derived products in the fight against cancer. These products are
cytotoxic to both common and uncommon cancer cells and even in some
animal models. Most of their cytotoxic activities involve the mechanism of
apoptotic induction by regression of anti-apoptotic Bcl-x protein, activation
of pro-apoptotic Bax protein, and enhancement in function of caspase-3
and p53 proteins; the major apoptotic pathway involved is intrinsic with
the employment of mitochondria in the process. Mechanisms of initiation
for damage of DNA and arrest of cell cycle via gathering of sub-G1 phase
cells also complement the mechanism of action of these products. The lim-
itation of most of the reported studies lack sufficient data from normal cells
to ascertain non-cytotoxic effects of these compounds on normal tissues.
However, this work shows the potential capacity of microalgae-derived
natural products to combat the public menace known as cancer.
It is recommended that these compounds be studied on normal cells
to determine their safety for use. Further in-vivo studies are also recom-
mended to be carried out on these impressive compounds.
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8
Current Research on Algal-Derived
Sulfated Polysaccharides and
Their Antiulcer Bioactivities
Abiola Mojisola Asowata-Ayodele1*, Adewale Omowumi Oyeronke2,
Akomolafe Seun Funmilola3† and Adetunji Juliana Bunmi2†
Department of Biosciences and Biotechnology, Faculty of Science, University of

1
Medical Sciences, Ondo, Ondo State, Nigeria

2
Department of Biochemistry, Faculty of Basic Medical Science,
Osun State University, Osogbo, Nigeria
3
Department of Biochemistry, Ekiti State University, Ado Ekiti, Nigeria
Abstract
Peptic ulcer disease has been characterized as a stomach ulcer that affects almost
the entire thickness of the mucous membrane. Natural therapies for the treatment
of gastrointestinal ulcers have been developed using medicinal plants and animals.
Due to the presence of its metabolites with high amounts of bioactive compounds,
phytoplankton has been shown to be beneficial in drug development. Seaweeds
are one of the roots from which botanical extracts are made, which make them
highly useful as a natural product in daily life. More nutritional compositions of
the aforesaid organisms especially need to be researched for the total eradication
of Helicobacter pylori so that peptic ulcers no longer afflict the population.
Keywords: Alginates, antiulcer, natural products, algae, peptic ulcer,

polysaccharides, seaweeds

†
This authors contributed equally to this work.
177
8.1 Introduction
The term “gastritis” refers to an inflammation or abscess that begins in
the mucous membrane of the stomach and extends across the muscularis
mucosae, generally characterized by various phases of coagulation [1].
Falco [2] defined duodenal ulcer (DU), pyloric canal ulcer (PCU), gastro-
intestinal ulcer (GU), and postoperative ulcer at the surgical anastomosis
site as a spectrum of illnesses.
Helicobacter pylori, a bacterium that lives in the acidic environment
of the stomach and colonizes the gastric mucosa, has been blamed for all
ulcer-related disorders since its discovery. The bacterium has a spiral-like
form and flagella, allowing it to travel continuously across the stomach’s
acid and mucous membranes [2].
H. pylori may attach epithelial cells to the plasma membrane of stomach
epithelial cells, destroying their cytoskeleton components. Without urease,
colonizing the mucosa with this substance and protecting the germs from
hydrochloric acid would be impossible [1]. Urease, a cytoplasmic enzyme
that acts intracellularly and is affine to gastric mucin, is abundant in micro-
bial cells. This enzyme activates neutrophils and monocytes, causing the
generation of various pro-inflammatory cytokines as well as the formation
of nitric oxide and oxygen radicals [2–5].
The majority of ulcer sufferers have abdominal discomfort. The pain
which usually does not radiate is localized in the epigastrium. The signs,
in reality, are neither unusual nor uncommon. Back pain might indicate
that an ulcer has migrated rearward or that the discomfort is pancreatic
in nature. Patients may feel a burning or hunger discomfort that builds
up over one to two hours, then gradually subsides. Certain drugs, such
as antacids, may provide brief relief. Meals, according to some, aggravate
the discomfort of stomach ulcers while alleviating the agony of duodenal
ulcers [6]. As a result, people with stomach ulcers avoid eating and lose
a lot of weight, but those with duodenal ulcers are unaffected. Although
these tendencies are prevalent, it is crucial to recognized that they are not
specifically characteristic of a disease condition. The nature of the symp-
toms makes distinguishing between helpful ulcers and stomach neoplasms
difficult.
Despite the fact that H. pylori is a documented cause of a variety of gas-
tric disorders, there is much controversy regarding whether it performs any
function in the pathogenesis of non-stomach infections (Figure 8.1) [3].
Others argue that H. pylori does not cause ulcers in sick people, but that the
bacteria disturb the stomach and duodenum’s safe secretions, causing the
Algal-Derived Sulfated Polysaccharides 179
H. pylori
Gastric acid
Pepsin
NSAIDS
Mucosa
Peptic ulcer Submucosa

Necrotic (Microscopic view)
cells Muscularis
externa
Blood vessel
Figure 8.1 Pathogenesis of peptic ulcer disease [7].
acid to leak out [8]. However, given the use of various traditional therapies,
this virus offers a severe challenge for medical study; it seems doubtful
that this pathogen can be killed in the human body system [4]. Due to the
intricacies of peptic ulcer disease, a new strategy for removing the causal
factor is always needed. The purpose of this chapter is to evaluate current
breakthroughs in the work of sulfate polysaccharides in marine species, as
well as their potential antiulcer bioactivities.
8.1.1 Symptoms of Peptic Ulcer Disease

The disease’s clinical manifestations are categorized as minor, moderate, or
severe [5], as described below:
• Mild: Not more than three stools in a day, with or without

blood stain, and a regular erythrocyte sedimentation rate
(ESR).
• Moderate: More than four stools in a day with minor sys-
tematic interruption.
• Severe: Bloody bowel movements more than six times a day
with more than 30 symptoms of systemic interruption such
as tachycardia, fever, anemia, or an elevated erythrocyte sed-
imentation rate [5].
In addition to the above-mentioned symptoms, peptic ulcer disease may

be exacerbated by the following factors.
a) Hypercalcemia
Hypercalcemia is a state of elevated body calcium levels. The hypersecre-
tory condition of stomach acid reported in Zollinger-Ellison syndrome
patients is directly related to hypercalcemia. Intravenous calcium infusion
causes stomach acid hypersecretion in healthy participants, according
to [9]. Calcium has also been demonstrated to induce gastrin secretion
directly from gastrinomas in vivo and in vitro [5].
b) Genetic Variables
The etiology of infectious disorders is heavily influenced by genetic differ-
ences. First-degree relatives of ulcer patients should have a greater rate of
improving ulcer infection than the general population. Duodenal ulcers
affect about 20% to 50% of individuals with a good family history; sufferers
of ulceration in the stomach frequently identify clusters of afflicted rela-
tives [7].
c) Smoking
The development of ulcer disease, complications, mortality, recurrences
and delayed healing are all strongly linked to cigarette smoking. Ulcer dis-
ease is two times more common in smokers than it is in non-smokers.
Peptic ulcer disease is caused by a combination of causes such as the close
link between H. pylori and smoking cigarettes. This is because cigarettes
may make people more vulnerable, reduce protective components in the
gastrointestinal mucosa, or create a more favorable environment in which
bacteria can thrive [1].
d) Anxiety
Because psychology’s place in the world isn’t well understood, several stud-
ies have shown conflicting results on the relevance of psychological ele-
ments in peptic ulcer disease pathophysiology and natural history. Acute
stress causes a rise in anxiety, blood pressure and heart rate; only individu-
als with ulcers in the duodenum have shown substantial increases in basal
acid production as a consequence of acute stress [7]. Ryan said the disease
doesn’t have a distinct “ulcer type” personality. Mentally, ulcer patients
are no different from the normal population, but their levels of stress are
higher. There is also no indication that the likelihood of developing an
ulcer is related to a person’s work and lifestyle [10].
e) Diet and Alcohol
Animal studies have shown that alcohol damages the stomach mucosa, the
amount of absolute ethanol administered seems to be one of the determin-
ing factors. Pure ethanol is lipid-soluble and causes severe, open mucosal
injury. Mucosal damage may occur at doses of less than 10% ethanol since
most individuals do not consume complete ethanol. Low quantities of
ethanol (5%), on the other hand, may increase stomach acid output while
greater concentrations inhibit it. While this is intriguing from a physiolog-

ical standpoint, it has no bearing on the cause of ulcers [5].
f) Gastrinoma (Zollinger-Ellison Syndrome)
Irritable bowel syndrome has been linked to certain foods and beverages.
No conclusive assertion has been made on the link between a specific diet
and ulcer disease. Cola, decaffeinated, caffeinated beverages or milk and
beer have not been linked to an increased risk of ulceration in epidemio-
logical research. Other than avoiding items that cause discomfort, dietary
changes are unnecessary [5].
Gastrinoma is a kind of cancer that affects the intestines (Zollinger-
Ellison syndrome). Abnormally located peptic ulcers, such as in the jeju-
num, severe oversecretion of stomach acid, and a pancreatic gastrinoma
are all symptoms of Zollinger-Ellison syndrome. Gastrinoma affects the
pancreas in around half of all individuals. Another 20% of patients have
it in the peri-pancreatic lymph nodes, stomach, ovary, liver, or small
bowel mesentery [5]. Only 0.1% of all duodenal ulcer illnesses are caused
by Zollinger-Ellison syndrome. As part of multiple neoplasia syndromes,
one-fourth of the patients have this disorder. Because gastrin is trophic
to the gastrointestinal mucosa, people with gastrinoma may have intrac-
table ulcer disease. Endoscopy or X-ray may reveal gastric hypertrophy.
Sufferers may present with diarrhea (with accompanied constipation) as
well. Diarrhea as a result of lipase inactivation by acid and reflux in the
gastroesophageal region are possible side effects. In 75% of patients, these
symptoms are episodic [7]. H. pylori affects roughly 20% of those under the
age of 40 and 50% of those over the age of 60 in general. It is not recorded
in young children; but is predicted for those of poor socio-economic posi-
tion. Immigration is to blame in certain western nations for the isolated,
densely populated places where it is more likely to occur.
8.2 Treatment Using Synthetic Medicines

Inhibiting stomach acid production, increasing gastro-protection to scav-
enge reactive oxygen species and eliminating H. pylori are all part of the
contemporary strategy for gastroduodenal ulcer treatment. Although
proton pump inhibitors (lansoprazole, omeprazole), receptor blockers
(famotidine, ranitidine, etc.), and antibiotics (amoxillin, clarithromycin,
tetracycline, and others) are currently used for efficient management of
the condition [11], there is currently no cure for it. However, the standard
treatment relies on reducing aberrant inflammation in the colon lining,
which reduces symptoms such as diarrhea, rectal bleeding, and stomach

discomfort. Therapy is tailored to the severity of the condition; as a result,
treatment is tailored to each person [5]. To decrease inflammation and
improve symptoms, most people with early stage or severe inflammatory
bowel disease are given corticosteroids such as dexamethasone [5]. After
one year, over a quarter of patients with ulcerative colitis who need steroid
treatment become steroid-dependent, and nearly all experience steroid-
related side effects [5]. Other immunomodulators (azathioprine and
6-mercaptopurine) that impact the immune system and amino-salicylates
to reduce inflammation are available.
Various classes of pharmacological drugs have been shown to be ben-
eficial in the treatment of acid-induced peptic diseases: Acid-suppressive
agents such as lanzoprazole and omeprazole; antacids such as magnesium
trisilicate and aluminum hydroxide; antagonist of histamine H2-receptor
such as ranitidine and cimetidine; cytoprotective agents such as sucralfate
and analogs of prostaglandin such as misoprostol; anticholinergic agents
such as pirenzepine; and antimicrobials (H. pylori eradication).
Ranitidine is a reversible antagonist of H2 receptor known to be highly
competitive and usually used for the treatment of peptic ulcers, Zollinger-
Ellison syndrome, gastroesophageal reflux disease, and other conditions.
Mahmoud found a link between oral and intravenous ranitidine infusion
and severe allergic responses such as toxic epidermal necrolysis, broncho-
spastic reaction, and exanthematous pustulosis [10].
The acute form of ranitidine responses involves mechanisms that are
both non-immunological and immunological, according to the literature.
Ranitidine-induced anaphylaxis is a multi-organ clinical condition marked
by the fast development of cardiovascular and respiratory symptoms as the
first life-threatening recognized signs in the majority of patients [10].
Scientists have highlighted the urgent need for a novel antiulcer medica-
tion derived from natural sources to replace the presently utilized pharma-
ceuticals of questionable safety and effectiveness. Medicinal plants, herbs,
spices, fruits and other natural products are considered potential sources
of supply to regulate and manage various inflammatory bowel diseases [5].
A large number of functional foods, secondary metabolites and medicinal
plants with antiulcer properties have been documented [10, 12].
Between natural sources, red algal components have a complicated
method for protecting against gastrointestinal ulcers that require therapy.
Overcoming treatment resistance to H. pylori is a critical healthcare prob-
lem, since eradication of the agent is difficult in 15–20% of instances. In
actuality, after 3–5 years, the effectively treated individuals were re-infected
with H. pylori. As a result, finding innovative strategies to combat this ill-

ness is critical.
The current materials indicate that research into the use of marine algal
polysaccharides for treating Helicobacter infections is promising since these
substances have bidirectional activity and are non-adhesive, non-toxic,
immunomodulatory, non-oxidant and non-inflammatory. Polysaccharides
derived from algae have a significant bactericidal action and may remove
biofilms generated by microorganisms because of the potency of polysac-
charides produced from algae, the products now accessible in the literature
are primarily synthetic. Since obtaining specimens with a standard struc-
ture is still a difficulty, there are no recognized medications based on such
substances [5].
Seaweed extracts and polysaccharides are frequently utilized in other
nations. Several authors recommend adding algae-related sulfated poly-
saccharides to useable food items for patients with Helicobacter pylori
infection. Polysaccharides, like sulfate, offer a number of advantages,
including a large supply of raw materials, a lower level of technological
expertise in separation and purification operations, high pharmacological
activity, and low toxicity rates [4]. Brown algae fucoidans from sulfated
polysaccharides have also been identified as the source of novel drugs with
similar actions, demonstrating sufficient potential when combined with
biomedical schemes for the treatment of infection caused by H. pylori [4].
8.3 Natural Products Used in the Treatment

of Peptic Ulcer
A wide range of medicinal herbs are used to cure ulcer-related disorders,
following are a few of them:
• Centella asiatica is a highly popular medicinal plant used

in Asia. It is known as gotu kola in China, and it is said to
have existed over 2,000 years ago as “wonder elixirs of cre-
ation.” In rats, C. asiatica leaf extracts of about 50 to 250 mg/
kg dose demonstrated a good gastroprotective effect against
indometacin-induced ulcers [1].
• Baccharis dracunculifolia, sometimes known as green prop-
olis, is a Brazilian plant. Its essential oil is high in both
oxygenated and non-oxygenated terpenes, and it has been
shown to have antiulcer effects in rats; lowering total area of
lesion, the index of lesion, and lesion percentage. It also low-

ers the quantity of gastric juice and overall acidity of lesion
as well as the volume of total acidity and gastric juice [1].
• Baccharis trimera: The anti-secretory and antiulcer action
of B. trimera is known as carqueja in Brazil. The aqueous
extract has previously been tested in a pylorus tourniquet
and stress-induced ulcer model.
• Helichrysum gymnocephalum blooms at 25 to 200 mg/kg in
Wistar rats with indomethacin-induced severe ulceration
reveals the extracts’ gastro-protective and anti-inflammatory
properties, despite its lack of antioxidant activity. It is argued
that triterpene alcohols should be present based on these
findings.
• Tanacetum larvatum is an endangered annual plant that
grows in unstable regions of Montenegro, Croatia, and
Albania. The phenolic extracts generated from T. larvatum
blooming aerial parts showed anti-inflammatory effective-
ness dose-dependently, with somewhat fewer gastrointestinal
lesions in ulcerated Wistar rats treated with indomethacin at
200 mg/kg. These effects might be due to different compo-
nents of the plant extracts inhibiting the transcription factor
NF-B from binding to DNA [2].
The maritime ecosystem, which spans around 70% of the entire surface
of the Earth, is home to half of the world’s biodiversity. Many pharmaco-
logically active compounds, such as phytochemicals, sulfated polysaccha-
rides, polyunsaturated fatty acids, proteins, bioactive peptides, sterols, etc.,
are abundant in the aquatic environment due to its vast abundance [9].
These marine bioactive compounds come from a variety of places, such as
seaweed, algae, champignons, and other aquatic plants.
8.4 Antiulcer Products Developed from Algae

Many aquatic species are important in phytomedicine because they contain
significant bioactive secondary metabolites that may aid in the creation of
novel pharmacological drugs. Algae are a diverse category of autotrophic
organisms that range from single to multicellular. They are main producers
and nutritional sources for a large number of people. Microalgae, such as
blue-green algae, dinoflagellates and bacillariophyta, and macroalgae, such
as seaweeds, are the two primary varieties [13].
Gamal is a green, brown, and red alga that grows in the water. Brown
(Phaeophyceae), red (Rhodophyceae), and green (Chlorophyceae) algae
are classified as seaweeds based on their pigmentation [14]. Both biodi-
versity and chemical diversity abound in the marine environment. Marine
organisms have identified a large number of new metabolites with powerful
pharmacological effects in recent years. Seaweeds, also known as microal-
gae, are thought to be a rich source of biologically active compounds that
are used for therapeutic and medical purposes. The rising number of novel
compounds produced by macroalgae is promoting marine science as a via-
ble study topic for medication development [11, 15]. Seaweeds are used
for a variety of purposes such as for animal and human consumption.
Potential anti-ulcerogenic and anti-inflammatory drug development has
lately focused on investigating the efficacy of extracts isolated from medic-
inal plants that are more active and safer to use.
Because they are regarded to be the true producers of biologically active
chemicals from marine resources, algae have been acknowledged in phar-
macology as bringing chemical and pharmacological novelty and variety
[9]. Natural chemicals obtained from edible algae may be hygienic to use
as anti-ulcerogenic and anti-inflammatory therapy in the stomach. This
is because algae contain physiologically active chemicals such as phloro-
tannins, polyunsaturated fatty acids, carotenoids, flavonoids, and phenolic
acids, as well as sterols and polysaccharides.
Polymers composed of monosaccharide units are known as polysac-
charides, which are joined together by glycosidic linkages. Hot water
extraction, alkaline extraction, and fermentation have all been used to
remove and produce polysaccharides [16]. A significantly larger field of
polysaccharide formation is also ensured by readily accessible resource
reports. These polymers are found in macroalgae cell walls and vary in
terms of the composition of the monomeric units, degree of polymeriza-
tion, glycosidic linkages and sequence of the sugar residue. Sulfate esters
are connected to polymeric units of fucose, rhamnose, galactose, and glu-
cose in some of the polysaccharides. Polysaccharides of this kind have a
variety of functional and structural activities, as well as defense roles in
plants. Polysaccharide bioactivities and pharmacological characteristics
are said to be intimately connected to their molecular configurations [16].
Alginate, fucoidans, agar, ulvans, laminaran and carrageenans are among
the polysaccharides found in brown and green macroalgae [17, 18].
By comparison with other algal groups, red algae are the most signif-
icant source of a variety of physiologically active metabolites. They are
abundant in many sections of the world’s coastal locations, providing a
great and unexplored prospect for novel therapeutic supplies. Red algae
have been found to contain active compounds that can help to increase
food inflammation and ameliorate food tract inflammation, avoid or treat
oxidative stress-induced stomach ulcers and cancers, reduce inflammatory
activity by blocking the development of inflammatory mediators, and trig-
ger stomach and colon cancer cell apoptosis [9].
8.4.1 Phycocolloids
The name phycocolloid refers to three primary compounds recovered from
brown and red seaweeds (alginate, carrageenan, and agar, respectively) [6].
Phycocolloids like alginic acid, agar, and carrageenan are the major com-
ponents of red and brown algal cell walls. They are found in many kinds
of seaweed cell walls and may be removed using hot water. Polymers com-
prising chemically modified sugar molecules, like agar and carrageenan
galactose or organic acids like mannuronic acid and algal glucuronic acid
in alginates, are examples of such phycocolloids. Humans and other ani-
mals may safely ingest most phycocolloids, as they are usually used to pre-
pare meals, including puddings, ready-mix cakes, and dairy toppings.
a) Alginates
Alginates (Figure 8.2) are a kind of sugar that may be found in brown
seaweed that is used to make alginates, whereas red seaweed is used to
make agar and carrageenan. Both acid and salt forms of algins/alginates
are accessible. An alginic acid or linear polyuronic is usually the acid form,
while the salt form is a major composition of the cell wall in brown sea-
weed, accounting for nearly 40–47% of the dry weight of algal biomass [6].
Anionic polysaccharides are alginates. They combine covalently (1–4)
linked -D-mannuronate with the C5 epimer-L-guluronate to form linear
blocks. The most common commercial alginate phaeophytes are Laminaria,
O-
OH O
O OH
O O O
HO HO O
O O-
m n
Figure 8.2 Chemical structure of Alginates.

Mycrocystis, and Ascophyllum. Other small sources may include Durvillaea,

Sargassum, Lessonia, Turbinaria, and Ecklonia [19].
Alginates or alginic acids which are usually collected from brown sea-
weeds are used in ice cream to prevent the formation of ice crystals (pro-
duce a smooth texture). Alginates have been used in folklore medicine to
heal wounds and stomach ulcers [20]. Alginate also lowers cholesterol lev-
els in the blood. Alginic acid has been shown to block mast cell degranula-
tion and hyaluronidase, both of which are implicated in allergic responses
[8].
In various countries, including Germany, United States, Japan, Canada,
Belgium, etc., patents protect the treatment of gastroduodenal ulcers and
gastritis with the use of alginic acid and other compounds derived from it,
as well as the use of alginates as antiulcer treatments [6].
In humans, certain medicines containing alginate have proven to be
efficiently able to prevent acid reflux after eating, duodenal ulcers and bile
acid aggregation. Examples of such medicine include “Gaviscon” made of
sodium alginate, sodium bicarbonate, and calcium carbonate; “Algitec”
made of sodium alginate H2 antagonist, and “Gastralgin” made of sodium
alginate, alginic acid, and aluminum hydroxide [20].
In children aged 4 to 15, clinical trials demonstrated that sodium algi-
nate lowers inflammation, improves stomach mucous membrane regen-
eration, eradicates mucous membrane Helicobacter pylori colonies, and
normalizes resistance in nonspecific mucous membrane [6]. A “suspension
of polaprezinc-sodium alginate” as a high-performance combination for
treating severe gingivostomatitis (cold sores) aggravated by hemorrhagic
erosions and ulcers. In functional gastroenterology, mixtures of alginates,
alginic acid and antacids are used to treat epigastric burning and gastro-
esophageal reflux [6].
b) Carrageenans
Carrageenans (Figure 8.3) are often employed as a food additive, but
they’ve also been utilized in animal clinical trials to develop pleurisy and
colon ulcers. Carrageenans function in the formation of colonic ulcers is
controversial, and it seems to be highly reliant on the chemical properties
of the carrageenan [6]. Carrageenan from red algae is a linear SP made up
of 3,6-anhydro-D-galactose and D-galactose [23].
c) Agar
Agar (Figure 8.4) is a polysaccharide combination made up of agarose and
agropectin that has structural and functional characteristics that are com-
parable with carrageenans. It’s made from red sea algae like Gelidium spp.
and the species Gracilaria [6].
HO OH
OSO3-
O
O
O
OSO3- O
HO
OSO3
Figure 8.3 Chemical structure of Carrageenan.
OH
HO O
O
O
OH
O
O
H OH HO
Figure 8.4 Chemical structure of Agar.
8.4.2 Fucoidan
Fucoidan (Figure 8.5) is a sulfated polysaccharide that is usually found in
marine brown algae, sea urchin jelly coat shells and sea cucumber body
walls. It’s most typically found in the brown seaweed cell walls, but not in
other higher plants or algae and is mostly made up of sulphated L-fucose,
with less than 10% other monosaccharides.
Fucus vesiculosus, a type of brown algae fucoidan, was the focus of much
of the study on its biological activities [8]. It was discovered that fucoidan
from Fucus vesiculosus has substantial biological effects on mammalian
cells. Turbinaria conoides, Cladosiphono kamuranus, Fucus vesiculosus,
Undaria pinnatifida and Laminaria japonica have all been shown to con-
tain fucoidan [21].
Another researcher found that algal fucoidans had either alternat-
ing (13)- and (14)-linked-L-fucopyranosyl residues or repetitive (13)-
linked-L-fucopyranosyl residues in their homofucose backbone chains.
In addition to sulfonate- and acetyl-groups, as well as L-fucopyranosyl,
D-glucuronopyranosyl, and algal polysaccharides, some additional sugar
H3C HO
O H3C
-O SO
3
OSO3- O
O
OSO3-
Figure 8.5 Chemical structure of Fucoidan.
residues of the backbone’s L-fucose units occur in O-2 and/or O-4 [22].
Seaweeds were the first kind used to isolate fucoidans with backbones.
Fucoidans from Fucus evanescens, Fucus distichus, and Ascophyllum nodo-
sum have a second backbone type.
Cladosiphon okamuranus from fucoidan was shown to be more effec-
tive than F. vesiculosus in curing ulcers. The pathogen Helicobacter pylori
is only found in humans. It infects human stomach epithelial cells and
has been associated with significant upper gastrointestinal illnesses.
According to a research study, fucoidan (1.5–4.5 mg/kg•day) alleviated
non-ulcer dyspepsia symptoms, as judged by a structured review. During
this investigation, no major side effects from fucoidan were identified.
The authors claim that taking fucoidan on a regular basis helps with
non-ulcer dyspepsia [8].
Ex-vivo experiments with mice with H. pylori-induced gastritis revealed
that the brown algae fucoidans, F. evanescens, Cladosiphon okamuranus,
and F. vesiculosus, relieved the condition in people. Besednova found that
fucoidans significantly reduced H. pylori cycle adherence to the mucous
membrane in the stomach mucosa. At pH 2.0 and pH 4.0, brown algae
fucoidan from C. okamuranus decreased H. pylori adhesion to the gastric
mucosa in pigs, but the other two fucoidans utilized in these trials only
inhibited attachment at pH 2.0. H. pylori adherence to the head was not
inhibited by non-sulfated polysaccharides (dextran and mannan) or car-
boxylated polysaccharides [4].
8.4.3 Ulvans
The term “ulvan” is derived from the original terms ulvin and/or ulvacin,
which were introduced by Kylin to describe various fractions of water-
soluble sulfated polysaccharides Ulva lactuca. Ulvans are highly charged
COONa H3C
O O
O
HO
HO OH
OH
Figure 8.6 Chemical structure of Ulvan.
sulphated polyelectrolytes containing a common disaccharide ingredient;

the aldobiuronic acid, [4)-D-glucuronic acid-(14)-L-rhamnose3-sulfate-(1].
Iduronic acid is also a sugar component. Ulvans have a molecular weight
ranging from 189–8,200 KDa [6].
Ulvans (Figure 8.6) are sulfated polysaccharides that are highly branched
and water soluble, with uronic acid, rhamnose, and xylose as their pri-
mary sugar monomers. Ulva rigida, Monostroma sp. and Ulva lactuca
are all probable sources of marine ulvans [21]. Ulvans are also sources of
iduronic acid, which is utilized to make heparin component analogues for
antithrombotic procedures. Ulvan has been reported to be used for treat-
ing stomach ulcers and as an anti-influenza medication [21]. Due to its
anti-thrombotic properties, it is used to diagnose gastric ulcers, stomach
ulcers, and as an anti-influenza agent [8].
Another study found that seaweeds had strong wound healing, antiulcer
and hepatoprotective properties. In investigations [12, 13], it was discov-
ered that L. papillosa provided the most protection against stomach ulcers
(81%) followed by Gracilaria crassa (76%) when compared to the usual
medicine ranitidine (90%).
8.4.4 Laminaran
Laminaran (Figure 8.7) is a linear polysaccharide glucan that is made up
of 13- and 16-glucose residues, with a ratio of 13:16 of roughly 3:1. It is
usually found in the fronds of the Laminaria saccharina plant, and to a
lesser extent in the plants Ascophyllum, Fucus, and Undaria. The amount
of material varies according to the season and environment, but it may
account for up to 32% of the dry weight. Laminaran does not bind or mold
other laminarans, nor does it produce a viscous solution. Its principal use
seems to be in medical and pharmaceutical applications [6].
HOH2C
HO O O H2C
HO HO O O
HO
O
n
OH
Beta-1,3 m
Beta-1,6
Figure 8.7 Chemical structure of Laminaran.
8.4.5 Xylan and Porphyran

Xylan has not yet been shown to be economically viable and just a few uses
have been identified. One of the 3- and 4-linked-d-galactosyl residues in
its disaccharide units, porphyran, is comparable to agarose; however, some
of the residues in porphyran are 6-sulfate [23]. Porphyra species have a
sulphated polysaccharide known as porphyran (Figure 8.8), which is part
of the galactan complex. Porphyran is a high-quality dietary fiber that is
chemically related to agar [6].
Porphyran is a sulfated polysaccharide found in the red algae Porphyra
vietnamensis, which may also be found in the red seaweeds. Porphyran
includes numerous major components that have a significant impact,
mostly through inhibiting Helicobacter pylori development [11]. To extract
and identify bioactive molecules that may have benefits in the inflammatory
(a)
HO OMe OH SO3–
O
O
O
OH O
OH
n
(b) O
HO OR
O
O
O O
OH OR
n
Figure 8.8 Chemical structure of Porphyran.

O O
OH OH
H H H H
HO HO
Taondiol
Isoepitaondiol
OH O
O
HO O
O
HO
Stypodiol
Stypoldione
O Sargaquinone
HO
Sagaol
Figure 8.9 Chemical structure of isolated secondary metabolites from marine alga
T. atomaria [21].
and therapeutic domains, further chemical study on the P. vietnamenis

aqueous and alcoholic fractions is necessary.
Among natural sources, red algal components have a complicated
mechanism that demands attention for protecting against stomach ulcers.
Porphyra is one of these algae that contains several important compo-
nents, especially via controlling H. pylori, which has a significant impact
on pathogen proliferation [11].
In MS/MS analysis of the methanolic extract of Gracilaria changii
(MeOHGCM), red algae extracts revealed the presence of methyl-
10-hydroxyphaeophorbide and 10-hydroxypheophytinea, recognized
chlorophyll proteins, and a number of unknown molecules [9]. During
U937 cell differentiation, treatment with 10 g/ml MeOHGCM6 extract sig-
nificantly reduced the degree of IL-6 gene expression and TNF-α reaction
with inhibitory activity that is comparable to that of a standard drug (beta-
methasone). No cytotoxic effects have been detected in cells treated with
the 10 g/ml MeOHGCM6 extract. When MeOHGCM6 extract was sup-
plied to rats at a rate of 500 mg/kg bw, the entire ethanol-induced stomach
lesions scale was reduced by > 99 percent (p 0.05). This shielding effect was
the same as that produced by OMP. The pH of the stomach mucus fell in a
dose-dependent manner from 5.51 to 3.82, with substantial increases.
The authors of various studies claimed that the mass spectrometric stan-
dardized methanolic extract of Gracilaria changii had gastroprotective,
anti-inflammatory, and anti-ulcerogenic effects [6, 9, 11, 12]. In the future,
more research into the extract’s active constituent and mode of action is
required.
According to a recent study on algae antiulcer activity, the aqueous extract
of Turbinaria conoides reduced gastric ulceration to 50.98 from 99.85% at a
dosage of 500 mg.kg-1 [24]. Seaweed acetone extracts from Gracilaria crassa,
Laurencia papillosa, and Turbinaria ornata showed antiulcer, wound-heal-
ing and hepatoprotective properties. Chemical structure of isolated sec-
ondary metabolites from marine alga of Turbinaria species include sagaol,
Sargaquinone, stypoldione, Stypodiol which showed in Figure 8.9. In com-
parison to Laurencia papillosa, G. crassa was notable since it displayed
noticeable and remarkable wound-healing and hepatoprotective activity, as
well as strong antiulcer activity. G. crassa has the potential to be of biomed-
ical significance.
8.5 Conclusion
Algae are a diverse category of aquatic photosynthetic creatures that make
up around 10% of the plant kingdom. Based on their biological structure,
they are classified as macroalgae (red, green, and brown seaweed) and
microalgae (tiny seaweed) (blue-green algae; normally unicellular organ-
ism). The three major forms of photosynthetic algae mentioned in this
work are generally fat-soluble producing organisms, which from ancient
times have been used for treating different ailments in humans. Since algae
are scientifically proven for the antibiotics activities they exhibit, scientists
have highlighted the urgent need for a novel antiulcer medication derived
from natural sources to replace the presently utilized pharmaceuticals of
questionable safety and effectiveness.
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pharmajournal.com
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673, 2013.
9
Pharmacological and Antioxidant
Attributes of Significant Bioactives
Constituents Derived from Algae
Juliana Bunmi Adetunji1*, Abigail Omotayo Agbolade1,
Omowumi Oyeronke Adewale1, Ikechukwu P. Ejidike2,
Charles Oluwaseun Adetunji3 and Isreal Olu Oyewole1

1

2
Department of Chemical Sciences, Faculty of Science and Science Education,
Anchor University, Lagos, Nigeria
3
Department of Microbiology, Biotechnology and Nanotechnology Laboratory,
Edo University Iyamho, Edo State, Nigeria
Abstract
Algae are marine or freshwater phytosynthetic microscopic organisms with fast
growing rate. Moreover, reports have revealed that they have diverse bioactive
substances which have proven potent in enhancing nutrients in food and feed,
promote good health, and serve to maintain economic sustainability in industries
over the coming years. Algae have been documented to be a reservoir for sev-
eral secondary metabolites such as terpenoid, taondiol, stypodiol, isoepitaondiol;
and hydroxycinnamic and cinnamic acids. In this chapter, the chemical structure
of some bioactive constituents used in the formulation of high-valued therapeu-
tic drugs and their benefit are documented. Also, some natural bioactives like
fucoidan, phycocyanin, phycocyanobilin, laminarin, fucosterol, saccharides, phlo-
rotannins, dieckol, D-isofloridoside and phycoerythrin from algae were revealed.
Applications of these bioactive constituents as immune booster, neuroprotective,
anti-inflammatory, antioxidants, anticancer, wound healing, antimicrobial, etc.,
were also stated.
Keywords: Algae, natural bioactives, pharmacological, antioxidant, health
197
9.1 Introduction
As a potent nutrient source of food and feed and a health-promoting sub-
stance, algae will continue to be a part of sustainable industrial development
with economic benefits in coming years. For instance, the commercially avail-
able, naturally rich antioxidant astaxanthin, which is derived from microalgae
(Haematococcus pluvialis), has diverse applications in industries like nutra-
ceuticals, cosmetics, food, and aquaculture. Also, astaxanthin has been doc-
umented to be significant in decreasing oxidative stress, thereby maintaining
the state of a person’s health. Therefore, astaxanthin will continue to play a part
in potent microalgal products in high demand for future use [1].
Furthermore, a complex polysaccharide called fucoidan (FUC) pro-
duced by brown marine algae has L-fucose and sulfate functional constit-
uents with therapeutic benefits in the management and treatment of many
human disorders. Due to its numerous chemical structures and antioxi-
dant potentials, it is used to formulate substances with high pharmacolog-
ical properties to manage and treat inflammation, cancer, diabetes, viral
and neurodegenerative situations [2]. Meanwhile, fucoidan involvement in
alterations of intracellular signaling pathways, ROS generation regulation,
and cell survival and death processes maintenance contributes to disease
prevention via the immunomodulatory and antioxidant capability of FUC
[2]. It was documented that FUC medicinal potential is due to the abun-
dant bioactive constituents with an enhanced confirmational structure that
contributes to the therapeutic potency of drugs synthesized from FUC [2].
Fucoidan is mostly sourced from brown algae and it is an extremely
hygroscopic negatively charged polysaccharide. Reports by Salehi et al.
documented that A. nodosum, M. pyrifera, L. digitata, and F. vesiculosus
leaves are high in FUC [3]. It was gathered that FUC could be soluble in
water and acids and advantageous in hepatocytes damage and urinary sys-
tem failure protection [4]. Fucoidan was reported to be a multifunctional
marine polymer by Huang et al., which is often extracted from seaweed
through solvent, acid, and high-temperature extraction [5]. This extracted
bioactive is strategically deployed in the prevention, management, and
therapeutic intervention of diseases [2].
9.1.1 Brown Algae

9.1.1.1 Fucoidan and Its Bioactivity
Huang et al. reported that fucoidan (FUC) derived from algae has lots of
biological activities that can serve as an antioxidant, anti-inflammatory,
Antioxidant and Pharmacological Capability of Algae 199
anticoagulant, immunomodulatory, etc. [6]. The authors demonstrated the

efficacy of fucoidan on microbiome and inflammation in high-fat-diet-
induced obese mice. FUC0.5(50mg/(kg.d) and FUC2.5(250mg/(mg.d)
of FUC were fed to mice for 35 days and it was revealed that the bio-
active substance in FUC suppressed the obesity in mice and restored tissue
damage via decline in the body mass index and weight, enhanced organ
index, liver steatosis, decreased body weight, and small intestine structure
enhancement.
Huang and colleagues also observed that FUC treatment caused a
decline in tumor necrosis factor-α, triacylglycerol, LDL-c, lipopolysac-
charides, cholesterol, and bile acid; but stimulated high-density lipopro-
tein cholesterol [6]. The authors revealed that it enhanced gut microbiota
structure and caused an abundance increase in Shannon diversity index,
Faecalibacterium prausnitzii, and evenness as examined via PCR and gra-
dient gel electrophoresis denaturation. Used as a functional food, FUC
could protect against obesity and modulate the microbiota of the gut [6].
9.1.1.1.1 Fucoidan Structure

An active substance derived from brown algae extracellular matrix is a
fucose-enriched sulphated polysaccharide referred to as fucoidan (FUC).
Moreover, FUC derived from diverse brown algae species consists of sul-
phate and L-fucose groups with small mannose, xylose, rhamnose, glucu-
ronic acid, galactose, glucose, and arabinose [7]. The synthesized fucoidan
is named after the composition of the monosaccharides, such as galacto-
fucan (galactose and fucose), rhamnogalactofucan (rhamnose, galactose,
and fucose) and rhamnofucan (rhamnose and fucose), and therefore
determines the variation in the structure of the seaweeds. Coronado-Reyes
et al. found that there are two forms of fucoidan: one with repeated units of
L-fucopyranose with 1→3 linkage and one with alternating and recurring
units of L-fucopyranose with 1→3 and 1→4 linkage [8].
The fucoidan obtained from brown alga (Sargassum thunbergia) was
used as a source of glucuronomannan oligosaccharides (Gs) and the
sulfated molecule was derived by sulfation to give sulphated glucurono-
mannan oligosaccharides (SGs). The authors found that the sulfation
process as observed through NMR techniques revealed in this increasing
order Man-C6 > Man-C4 > Man-C1R > GlcA-C3 > Man-C3 > GlcA-C2.
Furthermore, there was an assessment of superoxide and OH radical
scavenging activity, DPPH as well as the reducing power, but all have
higher degree of polymerization which enhanced their reactivity with
the exception of the hydroxyl radical quenching activity [9]. Their result
also revealed an increased sulfate content, low reducing power activity

and DPPH quenching power, while the opposite was seen in superoxide
radical quenching activity. In all, Gs and SGs antioxidant contents are
higher when compared with fucoidan and as such could be a key source
of antioxidants [9].
Also, Sargassum horneri serves as a fucoidan source and the products derived
from enzymatic transformation was over 20 kDa. Fucoidan was hydrolyzed by
recombinant fucoidanase FFA1, and its fraction of higher molecular weight was
fractionated with anion-exchange chromatography. Meanwhile, three diverse
molecular weights (63−138 kDa) of sulfated polysaccharides were obtained
[10] while NMR spectroscopy was used to analyze the structures resulting
in branched polysaccharide with repeating →3-alpha-L-Fucp(2SO3−)-1→4-
alpha-L-Fucp(2,3SO3−)-1→ fragment backbone and alpha-L-Fucp-1→2-
alpha-L-Fucp-1→ or alpha-L-Fucp-1→3-alpha-L-Fucp(4SO3−)-1→ units
side chains linked to the Carbon 4.
Interestingly, the F3 fragment differs in its side chain and molecular
weight from other FUC fragments with radiosensitizing and antican-
cer activities [10]. The interaction existing between chitosan/fucoidan
nanoparticles (CTS-FUC-NP) was established using Fucus evanescens algae.
The structure of the nanonized compound was ascertained by NMR spec-
troscopy. Moreover, about 55% of other fucoidan structures were contained
therein, which include a long-sulfated sequence of α-L-fucopyranose frag-
ments at Carbon 2. Furthermore, the influence of the FUC/CTS ratio on
the nanoparticles’ zeta potential and size was examined. The 3D model
structure of the FUC and CTS regular section was then carried out using
molecular docking to show whether the polymer occupies the complex
exterior depending on their ratio [11]. The authors also reported that the
thermodynamic parameters of the fucoidan-chitosan binding process indi-
cate that changes in FUC and CTS molecules conformation were observed
during the effective binding interaction [11].
9.1.1.2 Benefits Derived from Fucoidan

9.1.1.2.1 Neuroprotective
Kim et al. reported on the neuroprotective role of sulfated fucoidan derived
from brown algae on cerebral ischemia (CI) and its mechanism of action
via gerbil model of CI, which revealed that after 5 min, CI caused the
removal of pyramidal neurons in the hippocampal cornu ammonis 1
(CA1) [12]. Treatment with 25 and 50 mgkg-1 FUC was done via i.p./day
Antioxidant and Pharmacological Capability of Algae
.
201
for a period of 5 days prior to tGCI. The result showed that 50 mg/kg FUC
pretreatment decreased hyperactivity of CI-induction and guide CA1
pyramidal neurons against CI [12]. There was also inhibition of astrocytes
activations and microglia in the ischemic CA1 region by 50 mgkg-1 FUC
pretreatment. Consequently, a significant reduction of superoxide anion
radical and 4-hydroxy-2-noneal produced by 50 mg/kg FUC was seen in
the ischemic CA1 region with corresponding increase in superoxide dis-
mutase 1 and 2 (SOD1 and SOD2) expressions prior and after CI in the CA1
pyramidal neurons. Interestingly, treatment with SODs inhibitor (dieth-
yldithiocarbamate) with the FUC-treated gerbils, however, suppressed the
FUC-mediated neuroprotection. It was concluded that protective role of
FUC from CI is via the decrease in oxidative stress with corresponding
increase of SODs and activated glial cells attenuation by FUC results in
protection of CI [12].
9.1.1.2.2 Immune Booster

In another study, Jiang and colleagues isolated fucoidan from Stichopus
chloronotus (Sc), known as sea cucumber, and used it as a traditional tonic
food in southern China because of its high nutritive value [13]. It is the key
bioactive polysaccharide in the plant which has proven to be effective in
immune activation when studied on RAW264.7 cells. The authors observed
that Fucoidan isolated from Sc could activate RAW264.7 cells through
stimulation of TNF-alpha, Interleukins-6, NO, and Interleukins-10 pro-
duction. Toll-like receptors 4 and 2 (TLR4 and TLR2) were observed from
the RT-PCR analysis, which assist fucoidan-Sc enhancement in the down-
stream NF-κB signal pathway [13].
More so, the observed molecular weight and chemical structure revealed
Fucoidan-Sc’s major role in NO production enhancement. The study found
that FUC-Sc degraded product with molecular mass 113.1 × 104 Da activ-
ities were more than of the intact FUC-Sc resulting from the peak chain
length. Jiang et al. therefore found that the immunostimulating activity of
FUC-Sc could be through activation of TLR2/4 in the NF-κB pathway [13].
The pharmaceutical and food industries have seen polysaccharide derived
from marine algae as a potent therapeutic source. The substance consists
of a sulfate group and L-fucose that contributes to its excellent bioactive
function as anticoagulant, antitumor, antithrombotic, anti-inflammatory,
immunoregulatory, and antiviral [14]. Fucoidan has been established to
be protective to gastrointestinal tract, bone health, angiogenesis, and eases
metabolic syndrome.
9.1.1.2.3 Anti-Inflammatory
Zhu et al. isolated different Mw fucoidan from Holothuria tubulosa (Ht-FUC)
and then investigated Ht1/2/3/4 chain conformation in metabolic inflam-
mation via a co-cultured medium of macrophages and adipocytes in vitro
[15]. The authors confirm the efficacy of Ht-FUC in vivo using obese mice
maintained on a high-fat with sucrose diet (HFD w/Suc). However, the
result revealed Ht-FUC’s capability in enhancing co-cultured macrophage
M2 phenotypic polarization via the activation of PPARγ. Ht-FUC also
degrades lipids present in the adipocytes of the co-culture through TLR4/
NF-κB-dependent pathway inhibition [15]. In-vivo study of Ht-FUC estab-
lished the reduction in serum inflammation concentration lessened liver
Kupffer cells M1/M2 polarization as well as inflammatory infiltration of
adipose tissue epididymal. Ht-FUC was documented to have an amelio-
rative metabolic function on macrophage polarization and lipid catabo-
lism lysis through improving FFA-induction in the co-cultured system and
obese mice [15].
9.1.1.2.4 Antidiabetic
Another potential source of fucoidan bioactive is Ecklonia maxima. The
compound FUC which is sulfated polysaccharides was documented to
have several health benefits like in diabetes. In 2020, Daub et al. worked on
hot water extraction of FUC from Ecklonia maxima and obtained 6.89%
FUC containing L-fucose and sulfate (4.45 ± 0.25% and 6.01 ± 0.53%) with
about 10 kDa molecular weight obtained from the water extraction [16].
The authors also reported that the integrity and structure of the obtained
FUC are analogous to the previously reported one. The activities of car-
bohydrate digestive enzymes (alpha-amylase and α-glucosidase) were also
investigated, and the result revealed that FUC at 0.27–0.31 mg.ml-1 IC50
range is a strong mixed-type inhibitor of α-glucosidase and a stronger anti-
diabetic than acarbose in managing type 2 diabetes [16].
9.1.1.3 Laminarin
The brown marine algae dispersed among numerous seas in the world was
observed to contain a high level of bioactive constituents which include ώ-3
fatty acids (FAs), polysaccharides, polyphenols, and carotenoids. Reports
have shown that laminarin (LAM) formed through glucose monomers
linkage byα-1→3 and β-1→6-glucosidic bonds is the stored form of car-
bohydrate mainly present in brown algae. LAM and LAM oligosaccharides
are made up of 2–10 monomers and they have various biological activities
and prebiotic properties [17]. Also, LAM and LAM oligosaccharides are
important precursors for the production of bioethanol, which consists
of lots of glucose monomers. It could be documented that brown-algae-
derived LAM and LAM oligosaccharides have numerous uses in medicine,
cosmetics, food, and bioenergy fields [17].
9.1.1.3.1 Laminarin Quantification

Becker et al. documented that marine alga releases several glycans with
enormous biological functions as carbon and energy requirement for het-
erotrophic microbes [18]. The glycan organic matter was analyzed after
being hydrolyzed to measurable monosaccharides. Also, to quantify the
laminarin in the organic matter, glycan was digested via the use of selective
enzymes. The data gathered from environmental metaproteome showed
that the active enzymes carbohydrate derived from marine flavobacteria
as substrates for algal-glucan laminarin hydrolysis, which yielded glucose
and oligosaccharides as a product of digestion. The cloning of new gly-
coside hydrolases (GHs) from Formosa bacteria, two of which are endo-
-1→3-glucanases from GH16 and GH17 families, with that from GH30
an exo--1→6-glucanase, were then expressed, purified, and characterized
[18]. The significant strain of Hel1_33_131 GH30 derived from Formosa
sp. hydrolyzes the 1,6-glucose side chains, while -1,3-glucose of the lam-
inarin was hydrolyzed by Formosa agariphila GH17A and GH16A strain.
The authors observed that specificity profiling of FaGH17A and FbGH30
with the glucan oligosaccharides and polysaccharides library revealed
the enzyme high specificity but FaGH16A caused complex glucans and
-1,4-glucose hydrolysis. It was then resolved that the two strain above are
more specific for laminarin quantification.
9.1.1.3.2 Benefit Derived from Laminarin

9.1.1.3.2.1 Antioxidant
Brown alga (Sargassum thunbergia) was exploited by Hu et al. and was
claimed to have an oligosaccharides compound having high proportion of
bioactives. Beta-1,3-glucanase derived from bacteria around marine water
can serve as a tool that degrades LAM present in brown algae cell wall
[19]. Beta-1,3-glucanase (laminarinase), MaLamNA was cloned, expressed
and characterized by the authors from Microbulbifer sp. ALW1 in marine
bacterium. Phylogenetically, ALW1 shows a clear difference of glycoside
hydrolase families of a characterized laminarinase. However, expression
and purification of 57.3 kDa recombinant laminarinase was heterolo-
gously done on Pichia pastoris GS115 cells [19]. The hydrolytic function
of MaLamNA was exerted against LAM and its highest activity revealed at
pH 4.5–5.5 and 45 °C respectively, while it has extreme adaptability against
high acidic and alkaline pH upon exposure. It was found that dithiothreitol
(reducing agent) addition could boost MaLamNA activity significantly.
The product obtained from MaLamNA hydrolysis of laminarin exhibited
great antioxidant activities when compared with the undigested LAM. The
above activity of MaLamNA support it use as industrial resources in LAM
bioresource development [19].
9.1.1.4 Fucosterol
Fucosterol derived from the brown algae Eisenia bicyclis has various benefits
such as anticancer, antioxidant, and antidiabetic potentials. Interestingly,
Mo et al. examined the protective functions of derived fucosterol pre-
treatment on acute liver necrosis induced in mice by Concanavalin A
(ConA) with its molecular mechanisms of action [20]. Acute liver necrosis
in BALB/c mice was induced with ConA (25 mgkg-1) while doses of 25,
50, and 100 mgkg-1 of fucosterol prepared with 2% DMSO were admin-
istered daily orally. The authors measured apoptosis, liver necrosis, and
autophagy linked inflammatory cytokines at 2, 8, and 24 h. Fucosterol was
found to have reduced liver marker enzymes, necrosis of the hepatic and
interleukins-6, TNF-α, and interleukins-1β induced apoptosis. However,
fucosterol was also noticed to suppress apoptosis as well as autoph-
agy through Bcl-2 by upregulation, and reduced the level of functional
Beclin-1 and Bax. In addition, NF-κB and P38 MAPK signaling reduc-
tion was accompanied by activation of PPARγ. All the authors observed
that attenuation of injury of the liver caused by ConA is via P38 MAPK/
PPARγ/NF-κB signaling suppression, which contributed to its potency as
therapeutic agent in liver injury management or treatment [20].
9.1.1.5 Saccharides
9.1.1.5.1 Alginate Oligosaccharides
In another experiment, Li et al. studied the beneficial potentials of
extracted alginate oligosaccharides from Sargassum species on β-glucan
isolated from Sparassis latifolia and was characterized via nuclear mag-
netic resonance spectroscopy [21]. It was used to refine sodium alginate
from three species of brown marine algae, S. fusiforme, S. fulvellum, and S.
horneri, and it was found that mannuronate produces guluronate (M/G)
ratio (0.64 to 1.38). The fractions of oligosaccharides derived were solid
fraction (SF), ethanol fraction (EF), and liquid fraction (LF), which were
obtained from acid hydrolysis but analyzed through high-performance
anion exchange chromatography using a pulsed amperometric detector
and spectra of Fourier transform infrared (FTIR) spectroscopy. The S. fusi-
forme solid fraction gave the highest hydrolysate but low LF, while the M/G
ratio was consistently on the high side [21]. The SF of S. fusiforme and LF of
S. horneri were chosen for elicitation on S. latifolia, resulting in high yield
of β-glucan ranging from 56.01 ± 3.45% to 59.74 ± 4.49%, respectively, in
the stalk. Also, S. latifolia aqueous extract had antioxidant activities. Total
polyphenol content, superoxide dismutase activity and 2,2’-Azino-bis(3-
ethylbenzthiazoline-6-sulfonate) radical quenching were triggered by algi-
nate. Therefore, the extracted alginate oligosaccharides from brown algae
could serve to improve mushroom nutritional value [21].
9.1.1.5.2 Polysaccharides
Polysaccharides possess anti-inflammatory, antioxidant and immuno-
modulatory potential. However, sulfated polysaccharide (PS) derived
from the brown algae Turbinaria ornata was obtained at doses of 2.5,
5, 10 mgkg-1bw for 7 days prior to systemic inflammation induction
with 10 mgkg-1 i.p. lipopolysaccharide (LPS). Thereafter, samples were
subjected to molecular, biochemical and histopathological assessment.
Some biochemical as well as molecular parameters, like AST, γGT, GSH,
CK-MB, SOD, Grx, NFκB, LPO, IL1β, PI3k, IL6, IL10, iNOS, and Akt,
were identified to determine PS mode of actions. The pretreatment with
PS caused a significant suppression of the activities of CK-MB, AST and
γGT raised by LPS in serum, while the level of mRNA, LPO, Grx, and
IL6 were also reduced in the heart [22]. Upon induction with LPS a sig-
nificant decline was seen in the activities of GSH and SOD. The PS also
reduced IL6, thioredoxin (Trx), and elevated IL10 mRNA measurement
in the heart, which supports its antioxidant and anti-inflammatory role.
The PS also modulate the proinflammatory markers (IL1β and NFκB),
oxidative marker (iNOS), and pPI3k/pAkt expressions majorly in the
cardiac region, hence contribute to the immunomodulatory potency.
Furthermore, an improvement was seen in the inflammatory pathology
of the heart tissue when compared with the LPS control, as observed
in histopathology analysis. Bhardwaj et al. documented that Turbinaria
ornata macroalgae PS prevented LPS-induced inflammation systemati-
cally in the cardiac tissue, which could be attributed to the presence of
glucopyranose and fucopyranose subunits [22].
9.1.1.5.3 Heteropolysaccharide
In 2019, Zhang and colleagues reported that an upsurge in oxidative stress
aggravates the aging process, hence the need to work on potential ways to
reverse oxidative damage to cells in order to promote longevity [23]. The
authors conducted their study on isolated Sargassum fusiforme heteropoly-
saccharide (SFPS) from brown algae in mice to suppress oxidative dam-
age in their aging process. However, it was claimed that no report exists
demonstrating the ability of SFPS to extend organism lifespan. Also, the
SFPS component that enhanced the antioxidant activity responsible for
the mechanism action was also not documented. The in-vitro radical scav-
enging assays carried out in this study revealed that fractions II of SFPS
(SP2) exhibit strong antioxidant potentials [23]. Also, the survival rate of
D. melanogaster exposed to stress was enhanced by a diet containing SP2
through significant improvement and reduced deposit of triacylglycerol at
older age. The activities of some antioxidant enzymes like SOD, glutathi-
one peroxidase (GSH-Px), and CAT were boosted by SP2 with a decline
in oxidized glutathione (GSSG) and malondialdehyde (MDA) level in old
flies. In addition, nuclear factor erythroid-2 like 2 expression levels and its
downstream target genes was upregulated by SP2 while revealing a decline
in Kelch-like ECH-associated protein 1 expression in old flies [23]. The
high rate of survival of D. melanogaster treated with SP2 supplement under
heat stress depends on the Nrf2/ARE route and the antioxidant potentials
of SP2, though this process was inhibited by the addition of Nrf2/ARE
pathway-specific inhibitors. It was concluded that SP2 derived from SFPs
could improve aging in D. melanogaster through the Nrf2-mediated anti-
oxidant signaling route [23].
9.1.1.6 Phlorotannins
Phlorotannins were isolated from a species of brown algae called Ishige foli-
acea, which has anticancer, antioxidant, and anti-inflammatory potentials.
Um et al. established the protective potential of phlorotannin-rich fraction
derived from I. foliacea (PFRI) for neurons in mice induced with memory
impairment using scopolamine. The authors administered supplementa-
tion containing 50 or 100 mgkg-1 PRFI for 42 days to scopolamine-induced
memory impaired mice. The PRFI supplemented diets suppressed the
activity of acetylcholinesterase and decreased lipid peroxidation levels with
a corresponding increase in SOD activity and glutathione concentrations
in the brains of mice [24]. PRFI triggers the regulation of brain-derived
neurotrophic factor and tropomyosin receptor kinase B expression level,
and extracellular cyclic AMP-response element-binding protein (CREB)

and signal-regulated kinase (ERK) phosphorylation of hippocampus and
the cerebral cortex involved in neuroplasticity. Consequently, PRFI is sug-
gested to hinder memory impairment induced by scopolamine via ERK-
CREB-BDNF pathway regulation and oxidative scavenging [24].
9.1.1.7 Dieckol
A phlorotannin called dieckol, which is extracted from the brown algae
Ecklonia cava, has antioxidant potential. Kang et al. described the antiox-
idant thermostability of dieckol at different temperatures of 30, 60, and 90
°C for a week with DPPH and OH radical quenching activities with respect
to its standard (ascorbic acid) [25]. The authors investigated apoptotic
body formation and reactive oxygen species quenching activity of dieckol
with DCF-DA assay, flow cytometry, propidium iodide and nuclear stain-
ing. Exposure of dieckol for a week revealed the stability of radical quench-
ing activities of DPPH and OH- radicals. Dieckol also showed its protective
potential against H2O2-induced apoptosis in Vero cells. Meanwhile, ascor-
bate revealed a decline in intracellular ROS and radical scavenging activi-
ties at 60 and 90 °C for the 4th and 3rd days, respectively [25].
9.1.2 Red Algae

9.1.2.1 D-Isofloridoside
Yang et al. studied the biologically active constituents of Laurencia undu-
lata, an edible red alga [26]. D-isofloridoside (DIF), an active compound
with matrix metalloproteinases (MMP) and antioxidant inhibitory prop-
erties having molecular weight 940.68Da, was derived from L. undulata.
The authors examined the processes used by DIF in the effective manage-
ment of tumor metastasis and angiogenesis in human vascular endothe-
lial cell (HUVEC) and HT1080 cell. DIF decreased the MMP-2/9 activity
with inhibition of hypoxia-inducible factor-1α (HIF-1α) gene through
mitogen-activated protein kinases and PI3K/AKT downstream regulation
routes. In turn, vascular endothelial growth factor (VEGF) was downreg-
ulated in CoCl2-induced HT1080 cell [26]. The bioactive component DIF
also suppressed VEGF receptor-2 expression, activated apoptosis, regulated
PI3K/AKT, MAPK, NF-κB signal downstream routes, and platelet-derived
growth factor (PDGF) production in VEGF-induced HUVEC was down-
regulated. It was then suggested that DIF could be a potent antitumor
functional food utilized for suppressing tumor angiogenesis [26].
9.1.2.2 Phycoerythrin
Phycobiliproteins (e.g., phycoerythrin) are a group of important pigments
isolated from red and blue-green algae. Reports revealed that food-derived
bioactive constituents have the capability of antagonizing dysregulated tar-
gets in cellular signaling routes, hence exhibiting antineoplastic capabil-
ities. Therefore, extraction of biologically active components from algae
and the pharmaceutical activity determination will assist in deducing and
predicting their specific molecular targets and also establish their safety or
toxicity in normal tissues.
Phycoerythrin (R-PE)-rich protein with hepatoprotective potential
was isolated from Portieria hornemannii and examined in vitro on HepG2
cells using H2O2 as inducing agent and in vivo on Wistar hepatocellular
carcinoma (HCC) rats. However, a dose-dependent decline was notice in
cell viability of HepG2 after H2O2 induction but its effect was reverse with
R-PE-rich extract treatment [27]. The enzymatic, non-enzymatic antioxi-
dants and the liver marker enzymes studied in the in-vivo experiment were
greatly suppressed in the induced HCC male Wistar rats after exposure to
a carcinogen (N-diethylnitrosamine (DEN)). Interestingly, R-PE-rich pro-
tein extract treatment caused reversal of the parameters in the carcinoma
rats. Moreover, alternative food supplements are beneficial in nutritional
therapy because of their chemo-preventive effects against the development
of cancer [27].
Phycoerythrin is a pigment protein extracted from Grateloupia filicina
a red alga which is a potent target that could be used in the management
and treatment of neurological disorders. In this experiment, astrocytes
were treated with phycoerythrin extracted from G. filicina (PEGf), it was
thereafter assessed for its antioxidative ability with H2O2. Hence, PEGf was
suggested to be effective on astrocytes’ viability and proliferation downreg-
ulated under oxidative stress, which in turn stimulate H2O2 [28].
9.1.2.2.1 Anticancer Potential

Gracilaria pygmaea serves as a potent source of antioxidants in the south-
west of Iran. In 2019, Hashkavayi et al. determined its antioxidant content
using phenolic content, and DPPH radical scavenging ability with the vol-
tammetric method [29]. The authors also carried out alteration of surface
carbon screen-printed electrode and electrochemical sensors production
with gold nanoparticles synthesis. The ability of the red algae extract to
suppress oxidizing agent was carried out with the use of ferrocene as the
target species. The phenolic and antioxidant content was evaluated by
electrochemical sensor to be 2.24 and 0.8 mgg-1. The extract was shown
to suppress radical and oxidizing compounds, while its anticancer activity
and effect were determined on MCF-7, HT-29, SKMES-1 and SKOV3 cell
lines with MTT assay [29].
9.1.3 Blue-Green Algae

9.1.3.1 Phycocyanin and Phycocyanobilin
Zheng et al. studied the antioxidative and renal protective potentials of
phycocyanin derived from blue-green algae (Spirulina platensis), and its
chromophore phycocyanobilin, whose structure looks like that of biliver-
din, was examined on type 2 induced diabetes in mice and rodents [30].
The experiment was carried out by pretreatment with 300 mg/kg phycocy-
anin for 10 weeks through oral route to guard against nephron mesangial
expansion and albuminuria in diabetes mice and rodents, and a normalized
fibronectin and tumor growth factor expression was seen. The bioactive
compound phycocyanin also ameliorated NAD(P)H oxidase expression,
and urinary and nephritic oxidative stress markers. Furthermore, admin-
istration of 15 mg/kg phycocyanobilin for 14 days through oral route
caused a suppression of NADPH-dependent superoxide release in nephritic
mesangial cultured cells. It was concluded that phycocyanin and phyco-
cyanobilin supplement could be a potent therapeutic approach in diabetic
nephropathy prevention [30].
A dietary inclusion capable of reducing the cholesterol level is Spirulina
platensis. The alga is also a rich in constituents of tetrapyrrolic compounds,
a key antioxidant and antiproliferative agent like bilirubin molecule. A
study done by Koníčková et al. evaluated the potency of tetrapyrroles
derived from S. platensis as an anticancer agent [31]. The antiproliferative
efficacy of phycocyanobilin (PCB) and chlorophyllin were also examined
on numerous cancer cell lines of human and xenotransplanted exposed
mice. S. platensis therapeutics efficacy was examined on mitochondrial
production of free radicals and glutathione redox status. The experimental
therapeutics in a dose-dependent manner triggered a significant decrease
in pancreatic cancer cell lines proliferation in vitro [31].
Blue-green algae are key constituents in the production of nutritional
supplements because they contain active and non-protein substances with
biological activity. Spirulina was documented to have numerous antiox-
idants like ascorbic acid, carotenoids and flavonoids, which exert a pro-
tective role against oxidative damage to cells. However, polyphenolic
compounds identified in blue-green algae were established to protect and
Table 9.1 Antioxidant compounds derived from algae.

S/N Class of algae Species of algae Antioxidant derived Function/uses References
1. Rhodophyta Osmunda spectabilis sp. Beta-carotene Antioxidants, anticancer, [33]
(Red algae) Porphyra perforate sp. antitumor use as
pharmaceutical additives and
food supplements
Stenogramme Carrageenans isolated Antiherpetic activity [34]
interrupta sp. from cystocarpic
and tetrasporophytic
plants
Carraguard, a Restricts in-vitro expression [35]
carrageenan-based of HIV and all sexually
microbiocide transmitted diseases
Chondrus crispus sp. Ascorbic acid Wound healing and aids [36]
collagen production, supports
immune system; Use in
food supplements
Mastocarpus stellatus Ascorbic acid Wound healing and aids collagen [36]
sp. production; supports immune
system
(Continued)
Table 9.1 Antioxidant compounds derived from algae. (Continued)

Kappaphycus alvarezii Vitamin A Cell growth and development [37]
sp. (wound healing properties),
supports vision, supports
immune system
Corallina sp. Polysaccharides Strong antiviral activity against [38]
possessing antiviral herpes simplex virus 1 and 2
activities
2. Phaeophyta Taonia atomaria sp. Terpenoids Antimicrobial, anticonvulsant, [39]
(Brown algae) Taondiol antioxidant, anesthetic, anti-
Stypodiol inflammatory, antiseptic,
Isoepitaondiol anticancer, antitubercular;
Hydroxycinnamic and disinfecticide; and anti-
cinnamic acids Parkinson’s activity
Sargassum sp. Ascorbate Antioxidant to protect cellular [40]
components from free radical
damage
(Continued)

Padina arborescens sp. Fucoidan-derived Strong antiviral activity towards [38,
Sargassum patens sp. polysaccharide from herpes simplex virus 1 and 2 41–43]
brown algae (HSV type 1 & 2)
Antiviral activity towards RSV
Anti-inflammatory compounds
Laminaria sp. Phlorotannins Anticancer, antitumor activities [44–46]
3. Chlorophyta Halimeda sp. Catechin Polyphenols with anti- [47]
(Green algae) Caulerpa sp. Epicatechin cardiovascular and anticancer
Gallate properties; Promotes brain
Flavonoids function; improves digestion
Dunaliella salina sp. Beta-carotene Antioxidants, anticancer, [48]
antitumor use as
food supplements
(Continued)

Chlorella vulgaris sp. Ascorbic acid; source The algae contain Chlorella [49]
of potential vitamins Growth Factor derived from
like water and fat- Chlorella RNA/DNA. It
soluble, e.g., A, B1, B2, triggers cellular regeneration/
B6, C, E, nicotinate, repair, aids collagen
biotin, folic acid and production, and supports
pantothenic acid immune system
Has preventive action on [50]
disorders like gastric
ulcers, atherosclerosis,
hypercholesterolemia, tumor
development and constipation
Haematococcus Carotenoids, Powerful antioxidant properties [51]
pluvialis sp. astaxanthin against free radicals and
oxidative stress; antiulcer
activities
Bryopsis sp. Kahalalide F (KF) Anticancer and antitumor [52–54]
properties
(Continued)

4. Blue-green algae Spirulina (Arthrospira) High protein content Anti-hyperlipidemia, [49, 55]
nephroprotective,
antihypertensive, growth
of intestinal Lactobacillus,
and elevated serum glucose
suppression
Suppresses HIV progression in [56, 57]
human T-cells, Langerhans
cells in the lymphatic systems
and other organs, peripheral
blood mononuclear cells; and
boosts immune system
Mucopolysaccharides Cardioprotective and cholesterol [58]
lowering potentials
recover neuronal cells’ functions via brain-derived neurotrophic factor

(BDNF) production in the brain glial cells [32]. In preparing Spirulina plat-
ensis aqueous extract, all the protein component was removed to have a
protein-free extract, whose effect was investigated on C6 glioma cells in the
BDNF gene transcription. It was noticed that the protein-free extract stim-
ulates the levels of BDNF mRNA via heme oxygenase-1 expression in the
glioma cells. The observed results then suggest that protein-free Spirulina
extract could control the brain function indirectly via glial cell activity
[32]. The antioxidant potential of algae is shown in Table 9.1.
9.1.4 Other Potential Applications of Algae

9.1.4.1 Antioxidant and Anti-Tyrosine Capabilities
Baek et al. evaluated 11 Sargassum species inhabiting the coasts of Korea to
determine their antioxidant and anti-tyrosine capabilities [59]. The author
found that the flavonoid content was from 2208–8233 × 10-2 mg querce-
tin equivalent/g dw, total phenolic content ranges from 2057–8897 × 10-2
mg gallic acid equivalent/g dry weight (dw), and anti-tyrosinase activity
between 1330-12630 × 10 -2 mg kojic acid equivalent/dw. However, S. hemi-
phyllum and S. miyabei Yendo had high total antioxidant content, though
S. miyabei Yendo contain tangible amounts of total flavonoid and phenolic
contents. Moreover, S. fillicinum and S. miyabei Yendo revealed the highest
anti-tyrosinase activity. Strong antioxidant capability was noticed in two
derived meroterpenoid compounds from S. miyabei Yendo and S. serrati-
folium, and so it could be mobilized for commercial usage [59].
In another study carried out on Halopteris scoparia biological activities
and the in-vivo toxicity of the various solvent extractions was carried out,
along with phytochemical screening and antioxidant determination of the
fractions. The cytotoxic activities of the extracts were tested on cell lines of
breast adenocarcinoma (MCF7), colon colorectal adenocarcinoma (CaCo-
2), and cervical adenocarcinoma (HeLa) using MTT assay method. The
total RNAs obtained for the gene expression analysis of the cell lines were
evaluated by high-tech equipment (Real Time Ready Human Apoptosis
Panel 96). Halopteris scoparia methanol extract toxicity and irritation
effects were determined by the acute lethal dose (LD50) test and hen’s egg
test using chorioallantoic membrane (HET-CAM) assessment respectively.
It was revealed from the results that the extract had 3320 ± 1.41 × 10-2
mg GAE/g and 126 ± 0.95 × 10-2 mg QE/g total phenolic and flavonoid
contents. The n-hexane extract in DPPH and methanol extract in ABTS+
showed high antioxidant activity while the MTT assay of the three extracts
resulted in a significant reduction in cell viability, especially in HeLa [60].

After treatment with the three extracts, the authors examined the apop-
totic gene expressions; pro-apoptotic genes in both caspase-independent
and caspase-dependent intrinsic and extrinsic pathways increased. In all,
edible H. scoparia showed no irritation and toxicity in vivo, and could be
used as a natural antioxidant for apoptotic/cytotoxic activities in human
cancers [60].
9.2 Conclusion
Algae as a reservoir of bioactive substances with numerous health bene-
fits could serve as an alternative source of bioactive in the development of
potent therapeutics that can be used to manage and treat numerous disor-
ders and enhance the function of the immune system.
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10
Utilization of Pharmacologically Relevant
Compounds Derived from Algae for
Effective Management of Diverse Diseases
Olulope Olufemi Ajayi *
Department of Biochemistry, Edo State University Uzairue, Edo State, Nigeria
Abstract
Algae are a diverse group of organisms containing various pharmacological com-
pounds. These compounds include pigments, such as phycobilins, chlorophylls
and carotenoids; polysaccharides, such as galactans, fucoidans and alginic acids;
proteins and fatty acids among others. These pharmacological compounds exert
anti-inflammatory, antioxidant, antiviral, antibacterial effects. etc., which are the
basis of their exploration as alternatives in the treatment of diseases. This is con-
tingent on the adverse side effects of conventional chemotherapeutic agents. In
this study, the pharmacological potentials of compounds derived from algae in
the treatment of certain diseases are discussed. There is evidence that these com-
pounds provide safer and more effective alternatives to the conventional drugs in
managing diseases.
Keywords: Algae, fucoidan, alginic acids, astaxanthin, fucoxanthin
10.1 Introduction
Algae are an assorted group of organisms that possess numerous bioac-
tive components. Their significance is based on their pigments, which
are categorized into carotenoids, phycobilins and chlorophylls, to which
their numerous biological benefits are attributed [1]. The following algae
have been reported to possess antioxidant properties: Macrocystis pyrifera,
*Email: [email protected]
223
Porphyra haitanensis, Bryopsis plumose, Laminaria ochroleuca, Bifurcaria

bifurcata, Rhodella reticulata, Ecklonia cava among others [2]. Among oth-
ers, the following algae were reported to possess anti-inflammatory prop-
erties: Ulva lactuca, Chlamydomonas hedleyi, Ishige okamurae, Undaria
pinnatifida and Eisenia bicyclis [2].
Oxidative stress and inflammation are connected and are linked with
diseases [3]. Oxidative stress induces transcription factors which could
enhance the expression of genes related to inflammation [4]. Evidence
indicates that oxidative stress-induced inflammation is related to the patho-
biology of chronic ailments [4].
Algal polysaccharides have been reported for their antioxidative and
anti-inflammatory properties, which enhance their therapeutic effects.
The most common brown algal polysaccharides are fucoidans and alginic
acids. Laminarans are also reportedly present in brown algae. Fucoidans
are sulphated branched polysaccharides usually found in brown algal cell
wall. They are biodegradable with highly minimal toxicity. Alginic acids
are linear copolymers made up of β-D-mannuronic and α-L-guluronic
acid residues [5]. They account for between 18 and 40% of brown algae
mass [6]. Laminarans are made up of β1-3-linked–D-glucose residues.
They account for between 10 and 35% of certain brown algae [7].
Red algae contain structural polysaccharides, including galactans such
as carrageenans, agars, porphyrin and xylan. Carrageenans are sulphated
polysaccharides containing galactose moieties and its derivatives. They are
the most researched algal polysaccharides [7]. The most prominent green
algal polysaccharide is the ulvan, which contains xylose, glucuronic acid,
rhamnose and sulphate [7].
Apo-9-fucoxanthionone extracted from Sargassum muticum brown algae
showed anti-inflammatory effect via mechanisms involving suppress-
ing nitric oxide and prostaglandin E2 production, as well as suppressing
IkB-α in macrophages [8]. This could be a potent therapy for inflammatory
illnesses.
Antineoplastic effect Sargassum muticum methanolic extract has been
reported [9]. Reduction in angiogenesis coupled with hindered breast can-
cer growth was observed in the study.
The antiproliferative and antioxidative effects of chlorophyta loaded on
albumin nanoparticle on MCF7 and HepG2 cell lines have been reported
[10]. This was evidenced by elevated levels of caspases 8 and 9 that sug-
gest apoptosis with the possible involvement of the granzyme pathway. The
principal bioactive constituent of this algae are phytocyanins. The study
suggested chlorophyta could be a potent anticancer therapy specific for
breast and liver cancers [10].
Algae-Derived Compounds for Disease Management 225
Phlorotannins are phenolic compounds derived from brown algae.

Major sources include Ascophyllum nodosum and Fucus vesiculosus. Their
antioxidant as well as anti-inflammatory properties are contributory to
their significant therapeutic outcomes. In a study, phlorotannins inhibited
benzo(α)pyrene-induced toxicity by inhibiting P2X7 receptor [11]. This is
suggestive of its cancer chemopreventive potentials.
10.2 Algae in the Management of Some Diseases

10.2.1 Cancer
Algae exhibit antioxidant mechanisms which have also been attributed to
their antineoplastic effects; including activation of apoptosis, triggering
nonspecific immune system, enhancement of the activity of natural killer
cell, halting of angiogenesis and cell growth, particularly at G1 phase [12].
Evidence showed that consumption of seaweed enhanced the activities of
superoxide dismutase and glutathione peroxidase enzymes [12]. Ethanolic
extract of Gracillaria corticata inhibited breast cancer growth via apoptotic
induction [12].
Certain studies have attributed algal anticancer effects to fucoidan.
Fucoidan exerts its antineoplastic effects via the following mechanisms:
suppression of neoplastic cells’ proliferation by altering mitosis, activation
of apoptosis, inhibition of VEGF expression, thereby inhibiting angiogen-
esis and activation of immune system, hence, boosting the efficacy of nat-
ural killer and T cells [13].
Fucoidan elicited apoptosis in colon cancer cells which is controlled via
both receptor-dependent apoptotic and mitochondrial death-dependent
pathways [14].
The stimulation of apoptosis in HT-29 cancer cells by fucoidan was also
reported in a different study. This was by mechanisms involving down-
regulation of IGF-IR, a major component of IRS-1/P13K/AKT pathway
[15]. Apoptosis was induced in MCF-7 cells by fucoidan via the induc-
tion of chromatin condensation as well as fragmentation of nuclear inter-
stitial DNA. Apoptosis could also be induced in MCF-7 cells via caspase
8-reliant pathway [16]. Inhibiting the expression of apoptosis-related
gene by fucoidan could also be a means of inducing apoptosis [17]. It also
reduces the transcriptional repressors, including Snail, Slug and Twit. This
also suggests the anti-metastatic potentials of fucoidan. Apoptotic initia-
tion in cancer cell can be via reactive oxygen species’ production. A report
showed apoptotic induction in hepatocellular carcinoma cells by reactive

oxygen species-mediated mitochondrial pathway [13].
There is evidence indicating the ability of fucoidan to inhibit cancer cell
proliferation. The proliferation of hepatoma cell lines BEL-7402 and LM3
treated with fucoidan was inhibited via the p38MAPK/ERK pathway. The
activation of P13K was inhibited by fucoidan, this led to the activation
of MAPK and the inhibition of ERK [13]. Report also showed the anti-
leukemic effect of fucoidan via inhibition of the cell cycle. The treatment
of NB4, a human acute myeloid leukemia cell, with fucoidan resulted in
the activation of CIP1, P21 and WAF1, which led to cell cycle arrest [13].
Bladder cancer (T24) cells were inhibited by fucoidan in a reported study.
Cancer cells’ viability was reduced via mechanisms involving triggering of
G1 cell cycle arrest [13]. In a study in which bladder cancerous cells were
treated with fucoidan, tumor growth was suppressed as evidenced by ele-
vated level of cyclin-dependent kinase inhibitor1 (p21WAF1) [13].
Fucoidan effectively suppressed the growth of melanoma B16 cell trans-
planted mice. Fucoidan suppressed VEGF expression; hence, inhibiting
angiogenesis [18].
10.2.2 Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is typified as a group of chronic state
of inflammation of the intestines without a known cause. Dysbiosis and
oxidative stress have been associated with IBD. It is a complex disorder in
which about 160 genes have been implicated [7].
Marine algae have been exploited for their therapeutic effects, particu-
larly in the management of IBD. Of importance is the anti-inflammatory
effect as well as the ability of algal polysaccharides to protect the gastroin-
testinal tract (GIT). This is because of their non-absorption in the upper
part of the GIT, resistance to gastric fluid and the activities of the digestive
enzyme [7].
Reports showed interleukin-17 (IL-17) has the primary pathogenetic
factor of IBD. IL-17 promotes both pro-inflammatory cytokines, IL-11,
IL-12, IL-23, IL-6, and anti-inflammatory cytokines IL-10 and TGF-β
[7, 19, 20].
Immune modulation potential of brown algae polysaccharides makes
them suitable as an alternative to conventional therapies in the manage-
ment of IBD [6].
10.2.3 Osteoarthritis
Osteoarthritis (OA) describes a progressive degenerative disorder of the
joints. The pain experienced by individuals with OA is due to inflamma-
tion of the joints. Mediators of pro-inflammation, including IL-1β, reactive
oxygen species and nitric oxide, are characteristic of OA [21].
Actinotrichia fragilis neutralized free radicals generated in OA in a
report. This is attributed to sulfated algal polysaccharides, antioxidant
amino acids (including glutamic acid, methionine, glycine and cysteine)
and histidine, an anti-inflammatory compound [21]. This is the basis of the
anti-inflammatory effects of A. fragilis [21].
Fucoidan extracted from Undaria pinnatifida significantly diminishes
degeneration of cartilage and bones in rheumatoid arthritic mice [22].
10.2.4 Gastric Ulcers

The gastroprotective and anti-inflammatory potentials of methanolic
extract of Gracilaria changii were reported. These properties were attributed
to pheophytin, as this extract contains methyl 10-hydroxyphaeophorbide a
and 10-hydroxypheophytin. Reduction of gastric acidity and alteration of
overproduction of macrophage-mediated pro-inflammatory cytokines are
plausible mechanisms [23].
10.2.5 Neurodegenerative Diseases

Neuroinflammation is implicated in the pathobiology of neurodegenerative
diseases. Ideally, neuroinflammation of neuro-immune cells (astrocytes
and microglia) is a mechanism of defense aimed at protecting the cen-
tral nervous system from trauma, injuries and infections. Conversely, pro-
tracted neuroinflammation has a potential of damaging the neurons [24].
Glial toll-like receptor (TLR) stimulation sustains neuroinflammation in
neurodegenerative disorders. The activation of TLR4 has been linked with
Alzheimer’s disease [24].
Algal bioactive components are being explored to target pathways of
neuroinflammation in the management of neurodegenerative diseases
[24]. Impediment of pro-inflammatory enzymes, mitogen-activated pro-
tein kinase (MAPK) pathway modulation and activation of NK-κB are
some anti-inflammatory mechanisms of marine algae [24].
In a report, astaxanthin ameliorated neuronal dysfunctions and

degeneration consequent on subarachnoid hemorrhage induced in mice.
Furthermore, the expressions of NF-κB, IL-1β, TNF-α were downregulated
[25]. In another study, astaxathin reduced the activities of neuronal nitric
oxide synthase (nNOS), cyclooxygenase-2 (COX-2) and inducible nitric
oxide synthase (iNOS) [26].
Floridoside extracted from Laurencia undulata impeded nitric oxide
and reactive oxygen species’ generation as well as reduced the activities of
iNOS mRNA and protein as well as COX-2 [27]. Phlorofucofuroeckol B
obtained from Ecklonia stolonifera impeded IκB-α/NF-κB and Akt/ERK/
JNK pathways [28]. Glycoprotein isolated from Undaria pinnatifida inhib-
ited Beta-secretase 1, AChE and BChE activities as well as enhances neur-
ite extension [29].
Dieckol obtained from Ecklonia cava downregulated p-38/NFκB path-
way [30]. Also, 8,8’-bieckol, dieckol and eckol from Ecklonia cava in another
study exhibited antioxidant and antiapoptotic effects [31]. Fucosterol iso-
lated from Padina australis inhibited Acetylcholinesterase (AChE) and
Butyrylcholinesterase (BChE) activities. It also impeded pro-inflammatory
cytokines’ expression [32]. Isolates from Sargassum polycystum, Padina
australis and Caulerpa racemosa also diminished the expression of pro-
inflammatory mediators [33].
10.2.6 Diabetes Mellitus

A high proportion of water and dietary fiber in algae makes them ideal
for diabetics. Furthermore, the colonic fermentation of undigested fiber
enhances the production of short-chained fatty acids that are of immense
benefit to health. Additionally, the ease of digestibility of algal starches to
disaccharides is beneficial [34].
Diabetic complications were reduced in mice administered fucoidan
from Saccharina japonica. This was via the hypoglycemic effect of fucoidan.
Furthermore, levels of TNF-α and IL-6 were also reduced in the animal
model [35]. In another study, IL-6 and TNF-α levels were lessened in dia-
betic mice treated with fucoidan and fucoxanthin [36].
10.2.7 Hypertension
Oxidative stress is involved in the pathogenesis of hypertension. Pro-
inflammatory effects of hypertension boost free radical production,
which may eventually reduce endothelial nitric oxide production [37].
Inflammation is the basis of endothelial disorder and ensuing endothelial

damage [38].
Reports have shown the antioxidant effects of some algae which also
exhibit antihypertensive effects. IQP, an angiotensin converting enzyme
inhibitor isolated from Spirulina platensis, showed a high free radical scav-
enging potential [39]. Furthermore, peptide isolated from Chlorella. vulgaris
effectively moped-up superoxide [40]. In another study, Chlamydomonas
reinhardtii lowered systolic blood pressure in hypertensive rats [41].
In another study, Phe-Glu-lle-His-Cys-Cys (FEIHCC) isolated from
Isochrysis zhanjiangensis impeded NF-κB, Akt and MAPK pathways, hence
inhibiting inflammation as well as inducing Nrf2 pathway upon angioten-
sin II application [42]. Activation of Nrf2 minimized the expression of
mediators of inflammation, including COX-2 and NO [43].
10.2.8 Atherosclerosis
The pathogenesis of atherosclerosis starts with vascular endothelial cell

dysfunction and, thereafter, the development of atherosclerotic lesions
[44]. Dyslipidemia is an aetiologic factor of atherosclerosis. Fucoidan
inhibited hypertriglyceridemia and hypercholesterolemia in apolipopro-
tein E-deficient mice while elevating the plasma concentration of HDL
cholesterol [45].
The elevation of plasma HDL level was by repressing the gene that codes
for fatty acid synthase and acetyl-CoA carboxylase in liver fat biosynthe-
sis [46]. Fucoidan also inhibited liver 3-hydroxy-3-methyl-glutaryl CoA
reductase activity [44].
Mediators of pro-inflammation were reduced while anti-inflammation
mediators were increased by fucoidan. The level of IL-6 was reduced in
apoE-knockout mice while the level of IL-10 was increased in mice fed
with fucoidan [44].
Fucoidan has also been reported to dissolve thrombus; hence, protect-
ing against atherosclerosis. Formation of thrombus has been implicated
in vascular diseases, including stroke [47]. Fucoxanthin inhibited the pro-
duction of oxidized LDL-induced endothelial damage [44]. Fucoxanthin
derived from Sargassum inhibited angiotensin-converting enzyme activity
[48].
In another study, seaweed phloroglucinol inhibited arachidonic acid-
mediated platelet aggregation as well as the formation of thromboxane B2
[49]. This is another antithrombotic effect of algae.
10.2.9 Kidney and Liver Diseases

Extract of Galaxaura oblongata was reported to exert a protective effect
against liver and kidney injuries in mice. This was via reduction of oxidative
stress and proinflammatory cytokines, including NF-kB [50]. Sargassum
polycystum extract assuaged hepatic and renal damages in diabetic rats at
150 mg/kg [51].
Dunaliella salina reduced liver inflammation and fibrosis in study ani-
mals. This was attributed to matrix metalloproteinase-9 stimulation and
concomitant reduction of tissue inhibitors of metalloproteinase [52]. A
report showed lower hepatic fat accumulation in rats fed with Spirulina
maxima-supplemented diet. Reduced LDL cholesterol was also observed
in these animals contrasted with animals in the control group [53].
Blue-green algae also inhibited nonalcoholic fatty liver disease (NAFLD)
development via mechanisms involving reduction in liver lipogenesis,
inhibition of lipid peroxidation and enhancing antioxidant enzymes’ activ-
ities [54].
A study on human subjects illustrated a converse relationship between
the consumption of algae and NAFLD [55].
10.2.10 Skin Diseases/Disorders

Phlorotannins extracted from Corallina pilulifera and administered to
human dermal fibroblast cells reduced ultraviolet (UV)-stimulated oxida-
tive stress in addition to the expression of gelatinases. Phlorotannins are
matrix metalloproteinase (MMP) inhibitors [56].
The anti-inflammatory potential of Nannochloropsis oculata on RAW
264.7 cells was characterized with reduction of iNOS in addition to COX-2
expression [57]. In another study, sulfated polysaccharides isolated from
Porphyridium impeded polymorphonuclear leucocyte migration and ery-
thema development [58, 59].
Reactive oxygen species (ROS) are implicated in skin’s aging. They acti-
vate MAPK that elicits transcription factor activator protein-1 phosphor-
ylation that leads to the upregulation of MMP, which ultimately results in
skin collagen degradation and its attendant skin aging [60]. Collagen is
essential for the sustenance of structural integrity of tissues. Wrinkling of
the skin is a consequence of deficit of type 1 collagen as well as expres-
sion of MMP-1 and elastase. This leads to the degradation of collagen and
elastin.
Inflammation occurs upon skin exposure to UV radiation. This causes alter-
ation in microvascular structure, vasodilation, leucocyte transendothelial
movement and loss of plasma protein [61]. Usually, elevated ROS gen-
eration in skin inflammation is protective of host cells and is aimed at
destroying the infective microbe [62]. Inflammatory response is a func-
tion of exposure to light’s specific wavelength. For instance, exposure to
UVB light elicits inflammatory responses in the keratinocytes via media-
tors; prostaglandin E2, nitric oxide, iNOS, TNF-α, COX-2 and cytokines.
There is now evidence that algal extracts exhibit anti-inflammatory effects.
Extracts from Ecklonia (E) kurome and E. cava inhibited nitric oxide stim-
ulation [30, 63]. Pro-inflammatory cytokines were inhibited by extracts of
Porphyridium spp. [2].
Extended exposure to UV radiation can initiate DNA mutations which
alter oncogenic functions, i.e., activating the oncogenes and inactivating
the tumor suppressor genes. This eventually results in cancer. Furthermore,
UV radiation alters DNA repair mechanisms by reducing DNA repair time
frame as well as inhibiting the activities of DNA repair enzymes [64].
10.2.11 Uterine Leiomyomas
Uterine leiomyomas (ULs) are nonmalignant tumors of the uterine tis-

sues that affect about 25% of reproducing women [65]. They are usually
symptom-free in a majority of women; there are, however, indications
that about 20% with UL have symptoms, including pelvic pain, recur-
rent urination and extreme uterine bleeding, thus reducing their qual-
ity of life [65]. Altered fertility was reported in some individuals with
ULs [66].
Hormonal, genetic and immunological factors have been implicated in
ULs growth. Uterine leiomyomas are characterized by an enormous pileup
of extracellular matrix (ECM), particularly transforming growth factor-β,
which enhances the accumulation of ECM components [67].
Recent studies have focused on the preventive and anti-inflammatory
potentials of certain polyphenolic compounds in the management of
ULs. This is considered a safer alternative to conventional therapies. In a
study, significant reduction was observed in UL cells treated with 0.5 mg/
ml of fucoidan. Cell cycle arrest at the subG1 phase was also observed.
Downregulation of proteins associated with ECM, including vimentin and
fibronectin, were also observed [68]. In another study, fucoidans impeded
TGF-B1-dependent epithelial mesenchymal transition (EMT) via ERK
pathway [69, 70]. Levels of connective tissue growth factor and fibronectin
were also reduced by fucoidans [70].
10.2.12 Obesity
Obesity is a global health challenge and a significant risk factor of cardio-
vascular diseases. It is defined as BMI ≥ 30.00kg/m2. The annual mortality
is about 2.8 million adults [71]. Sedentary lifestyle, genetic vulnerability,
and high-caloric diet consumption are factors implicated in its etiology
[72]. Therefore, therapies, including consistent reduction in caloric diet
intake and physical activity, appear to be effective in enhancing weight
reduction. However, consistency in maintaining a healthy lifestyle can be
quite challenging for a lot of people; hence, the need for effective chemo-
therapies with minimal adverse effects. Currently, phytochemicals are at
the center of research focus for affordable and safe alternatives to conven-
tional anti-obesity drugs [72].
Seaweeds are known sources of dietary fiber which are recognized for
delaying the rate of gastric emptying as well as plummeting rate of food
consumption. There is evidence of the anti-obesity potential of some algae.
There was a reduction in energy expenditure in a population of overweight
and obese females after being fed a diet supplemented with drinks rich in
alginate-pectin. This was attributed to the mechanism involving enhanced
satiety [73].
The appetizing effect of alginate was examined among study partici-
pants of various BMI categories. When sodium alginate was administered
to participants for 7 days, the study outcome showed a significant reduc-
tion in caloric intake. This suggests its anti-obesity potential [74].
There is evidence that fucoxanthin has the potential for weight reduc-
tion. In a study using rats and mice, weight reduction was observed in
animals fed fucoxanthin in comparison to the controls [75]. In a separate
study, fucoxanthin and its derivative fucoxanthinol inhibited the activity
of pancreatic lipase and reduced plasma triglyceride level [76]. Another
metabolite of fucoxanthin, amarouciaxanthin A, was observed to effec-
tively restrain the growth of white adipose tissue [77]. Xanthigen reduced
adipocyte lipid accumulation by the downregulation of principal proteins
of transcription factors in adipogenesis [78]. This also suggests its antican-
cer potential.
Spirulina is a cyanobacterium known for its numerous health benefits,
including maintenance of caloric homeostasis. It is rich in the antioxidants
phycocyanin, beta-carotene and the tocopherols. Gamma-linolenic acid is
the principal polyunsaturated fatty acid it contains [71]. There is evidence of
weight loss potential of Spirulina, which is attributed to its phytochemicals,
including phycocyanin. Phycocyanobilin present in phycocyanin inhibits
NADPH oxidase, an enzyme associated with induction of oxidative stress
in the cells of adipose tissues. The inhibition of this enzyme results in the
anti-inflammatory effects of Spirulina [71].
In a study involving 52 individuals that were obese, considerable weight
loss was observed after they were fed 2 g of spirulina/day along with a
low caloric diet for 3 months. In the study, low levels of a high-sensitivity
C-reactive protein and triglycerides were also observed [79]. In another
study of 62 obese individuals, reduced level of total cholesterol and ele-
vated level of HDL cholesterol were observed after been fed a diet contain-
ing 1 g of spirulina for 3 months [80].
In a study of 50 obese individuals placed on antihypertensive therapy,
the administration of 2 g of spirulina for 84 days led to a reduction in
their BMI and waist circumference [81]. Inhibition of infiltration of mac-
rophages to adipocytes, oxidative stress and fat accumulation in the liver
are plausible anti-obesity mechanisms of spirulina. Due to its high content
of gamma-linolenic acid, Spirulina inhibits accumulation of cholesterol.
The presence of niacin also enhances dyslipidemic conditions [71]. There
was a considerable diminution in blood pressure in hypertensive patients
that took 2 g spirulina within 12 weeks [82].
The anti-obesity potentials of macroalgae have been reported. In a study,
obese mice were administered Codium cylindricum, a green microalga with
high concentration of siphonaxanthin. A considerable reduction in body
weight and mRNA levels of lipogenic pathway genes were outcomes of the
study [83]. Reported obesity-reducing mechanisms of green microalgae
include reduction in adipogenesis and GIT absorption as well as enhanced
oxidation of fatty acid in the adipose tissue, particularly the white type.
For red microalgae, additional mechanism is enhanced thermogenesis in
brown adipose tissue [84]. In brown algae, enhanced lipid mobilization
within adipose tissue as well as an increase in oxidation of fatty acids in the
skeletal muscle are the reported mechanisms [84].
Phlorotannins are polyphenolic compounds found in brown seaweeds
[85]. They have also been reported to possess anti-obesity capacity via the
mechanisms described above, i.e., prohibition of differentiation of adipo-
cytes and pancreatic lipase inhibition. A report showed the ability of phlo-
rotannins to inhibit peptidyl prolyl cis/trans isomerase Pin1, which boosts
triglyceride uptake [86]. Therefore, inhibition of Pin1 can be targeted while
treating obesity-dependent ailments [85]. Phlorotannins can also inhibit
protein tyrosine phosphatase 1B, which relates to adverse insulin signal
transduction [87]. Eckol has also been reported to be a potent anti-obesity
compound.
Algal docosahexaenoic acid has been reported to exert a favorable effect
on the lipid profile of overweight and obese individuals. Its potency at a
lower concentration (2g/day) is equivalent to conventional DHA supple-

mentation at 4g/day for 42 days [88]. Momentous increase was observed
in the levels of particle sizes of HDL and large LDL and, conversely, reduc-
tion was observed in the levels of VLDL and IDL, which indicates positive
effects on cardiovascular health [88].
10.2.13 Tuberculosis
Tuberculosis is a bacterial infection which adversely affects the lungs and
other body organs. As of 2018, about 10 million people had tuberculosis,
out of which about 1.5 million people passed away [89]. Delayed diagno-
sis and noncompliance with therapies have been reported to exacerbate
the infection [90]. The principal challenge in the treatment of tuberculo-
sis is multidrug-resistant strains which often contributes significantly to
its mortality [91]. Antibacterial-resistant infections account for almost
700,000 annual deaths [92].
Antibacterial effects of algae have been described. Extracts of two
microalgae, Chaetoceros pseudocurvisetus and Skeletonema costatum, were
reported to possess anti-tuberculosis capacity [93]. The antibacterial effects
of fucoidans derived from Fucus vesiculosus L. have been eported.
This is via plausible mechanisms, including the binding of sulphated
polysaccharide to the surface of bacteria, hence resulting in bacterial cell
damage and nutrients leakage. Another mechanism is fucoidan’s ability to
trap nutrients, thereby hindering bacterial cells access to nutrients [92].
Nanotechnology has greatly enhanced the effectiveness of disease treat-
ment. This is because of its many merits, including improved drug bio-
availability, minimal side effects, and reduction in the frequency of drug
administration due to regulated and consistent drug release to target site
[89].
Anti-tuberculosis drug loaded on polypeptide micelles and alginate
nanocarrier was reported to be effective against Mtb H37Rv in compar-
ison with unloaded drug. In another report, amikacin and moxifloxacin
co-loaded on poly(lactic-co-glycolic acid and alginate significantly ham-
pered the growth of Mtb h37Ra cells as compared to individual drug.
Alginate-dependent nanoparticles significantly enhanced the antibacterial
effects of some drugs with minimal toxicity to key organs in another report
[89].
Anti-tuberculosis pulmonary drug delivery shows the potential of effec-
tive pulmonary tuberculosis treatment. Reduction in systemic drug toxic-
ity and specific site targeting of the drug are possible merits of this route
of drug administration. In a study, inhalable microparticles dependent on
fucoidan alongside isoniazid and rifabutin significantly impeded myco-

bacterial cell growth. This suggests fucoidan as a potential drug vehicle for
effective TB treatment [90].
10.2.14 Asthma
Asthma is a widespread respiratory inflammatory ailment worldwide with
a growing prevalence due to increased environmental pollution attributed
to industrialization. Asthmatic patients are allergic to pollutants, pollens,
mites and cold [94]. Shortness of breath, wheezing, tightness of the chest
and dry cough are frequent symptoms. Allergens further increase the sen-
sitivity and stimulation of the epithelial cells of the trachea, thus enhancing
secretion of mucous which could block the airway.
The levels of inflammation mediators, including TNF-alpha and IL-4,
are elevated in asthmatic patients, which are produced by swollen mac-
rophages and activated T cells of the lungs. The release of these cytokines
further enhances the inflammation of the epithelial cells of the trachea
as well as the production of mediators of inflammation, including eotax-
ins, cytokines and additional chemokines, that culminate in cell damage,
inflammation and alteration of the airway, which is the basis of worsening
breathing inconveniences experienced by asthmatic patients [94].
It is also pertinent to note that Th2 and ILC2 play a significant role in the
pathobiology of asthma as their activation and excessive production have
been implicated in massive production of IL-13, IL-4 and IL-5 [95], which
aid lung infiltration of eosinophils and mast cell induction. Production of
tracheal goblet cell by Th2 also aggravates mucous production capable of
blocking the airways [96]. Deposition of collagen in the lungs contingent
on sustained inflammation coupled with oxidative damage also caused a
breathing challenge in asthmatic patients [97].
Mechanisms targeting reduction of free radicals’ generation, inflamma-
tion and expression of Th2 are currently being explored in the manage-
ment of asthma. Current conventional therapies appear ineffective, hence
the need for more effective alternative treatments.
Extract of Eucheuma cottonii exerted anti-inflammatory, reduction in
mucin synthesis and pro-inflammatory cytokine production according to
a study [98]. Another alga, Eisenia arborea rich in phlorotannins, has been
reported to exert anti-allergic effects [99]. A report showed the initiation of
ERK1/2 and NF kB as well as suppression of Akt in platelet-derived growth
factor-activated airway smooth muscle cells by oligo-fucoidan [100].
Inhibitory effects of fucoxanthin on pro-inflammatory cytokines
have been reported [101, 102]. In another study, fucoxanthin inhibited
production of inflammatory cytokines with reduction in histamine and

IgE levels in asthmatic lab animals [31, 103]. There is evidence that fucox-
anthin ameliorated oxidative stress in asthmatic mice [94].
In a study, oligo-fucoidan boosted the levels of IL-10 and interferon–y
and also ameliorated the Treg/Th17 and Th1/Th2 imbalance [31]. It there-
fore provides an alternative adjuvant in the treatment of asthma.
10.2.15 Hepatitis
Lectin extracted from blue-green and red algae inhibited the growth of
hepatitis C virus. This antiviral property was attributed to scytovirin and
griffithsin, proteins with exceptional ability to bind several carbohydrate
moieties concurrently [104].
10.3 Xanthophylls
Xanthophylls consist of zeaxanthin, astaxanthin, fucoxanthin and
β-cryptoxanthin [1].
10.3.1 Astaxanthin
Chlorella zofingiensis, Haematococcus pluvialis and Chlorococcum sp. are
principal sources of astaxanthin [1]. The antineoplastic effects of astax-
anthin are reported. They include anti-proliferation, anti-oxidative, anti-
inflammatory, anti-metastatic and induction of apoptosis [105]. The
selective anti-proliferative impact of astaxanthin on cancerous cells and
not on normal cells has been reported [106].
The comparison of the astaxanthin with capsanthin, bixin and beta-
carotene showed that astaxanthin was more effective than other carot-
enoids [107]. Astaxanthin reduced cyclin D1 and proliferating cell nuclear
antigen expression in oral cancer cells [108].
Astaxanthin induced mitochondrial-apoptosis via hampering of anti-
apoptotic mediators; p-Bcl-2-associated death promoter and pro-survival
Bcl-2 [109]. Astaxanthin inhibited free radical production by augmenting
the activities of superoxide dismutase and catalase [110].
In a study, astaxanthin impeded NF-ΚB level, which led to inhibition
of pro-inflammatory cytokines’ production [105]. Astaxanthin reduced
mRNA and protein of MMP-2 and MMP-9, indicating its anti-invasion,
anti-migration and anti-metastatic properties [108]. Astaxanthin also
upregulated gap junctional intracellular communication while enhancing
the expression Cx43 protein [105].
10.3.2 Fucoxanthin
Fucoxanthin is a carotenoid found in marine algae with potent antioxi-
dant properties. Its peculiar structure consisting of an allenic bond and
5,6-monoepoxide distinguishes it from other carotenoids [111]. In a report,
fucoxanthin boosted nuclear factor erythroid 2-related factor 2 (Nfr2)
expression in ocular tissues. This was evidenced in/by the elevated activity
of SOD as well as reduction in the level of malondialdehyde contingent on
pathogen-associated molecular pattern (PAMP)-induced uveitis sugges-
tive of inhibition of oxidative stress [111]. Upon the liberation of Nrf2 into
the nucleus of cells, it fastens to the antioxidant response elements of DNA
to boost the activities of antioxidant enzymes [111].
The ability of fucoxanthin to protect against hyperglycemic-induced
diabetic retinopathy and the deleterious effects of 4-hydroxynonenal has
also been reported. The report illustrated that fucoxanthin enhanced cata-
lase activity, hence, reducing oxidative stress [112].
10.3.3 Lutein and Zeaxanthin

The primary source of lutein is microalgae [113]. It is a potent antioxi-
dant. Lutein as well as zeaxanthin are primarily found in Scenedesmus spp.,
Spirulina spp. and Chlorella spp. [1]. Galdieria sulphuraria and Dunaliella
salina are also rich sources of lutein [114]. Lutein impeded the high prolif-
eration rate of cells induced by ultraviolet radiation [115].
The antioxidant and anti-inflammatory potentials of zeaxanthin have
been reported [1]. Of note are reports of its photoprotection abilities [116,
117]. The antineoplastic mechanism of zeaxanthin in uveal melanoma
(UM) includes induction of apoptosis, inhibition of incursion and cancer-
ous cells migration via reduction in MMP-2 level [118].
Lutein and zeaxanthin inhibited oxidative stress in retina. Hence, it has
the potential of inhibiting diabetic retinopathy. Additionally, neuroprotec-
tion in diabetic retina by lutein has been reported [119]. Lutein and zea-
xanthin also inhibited lipid peroxidation in epithelial cell [119].
10.3.4 Beta-Cryptoxanthin
Beta-cryptoxanthin is an oxygenated carotenoid with similar structure to
beta-carotene. Its potent pro-vitamin A effect, antioxidant, anti-obesity
and anti-inflammatory effects are well known [1, 120].
Intake of β-cryptoxanthin reduced the risk of having type 2 diabetes
mellitus, according to a reported study conducted in Finland [121]. A study
carried out in Japan showed a considerably lower level of β-cryptoxanthin

in participants NAFLD. Administration of β-cryptoxanthin to these
participants lowered serum levels of markers of hepatic damage [122].
β-cryptoxanthin enhanced insulin sensitivity in non-alcoholic steatohep-
atitis (NASH)-induced mice. It also prevented hepatic fat accumulation as
well as inhibiting non-alcoholic fatty liver (NAFL) via improving insulin
resistance [123]. It also reduced inflammation and the production of mac-
rophages [123].
10.3.5 Siphonaxanthin
Siphonaxanthin is a carotenoid found in Codium fragile, Umbraulva
japonica and Caulerpa lentillifera. There is evidence of its potent antican-
cer effects on leukemia in comparison with fucoxanthin [124]. This was
attributed to the presence of an extra OH group on carbon-19 and absence
of epoxide in its structure. In a report, siphonaxanthin reduced the degran-
ulation of mast cell via the modulation of lipid rafts, thus showing its anti-
inflammatory effect [125].
10.3.6 Saproxanthin and Myxol

These carotenoids are known for their antioxidant potential. Additionally,
myxol enhanced biomembranes by inhibiting oxygen permeation [1].
Saproxanthin and myxol have been reported to possess potent antioxi-
dant potentials, which are attributed to their ability to inhibit lipid perox-
idation [120]. Saproxanthin can be converted to myxol by 2’-hydroxylase
[120].
A report showed higher antioxidant activities of saproxanthin and
myxol than zeaxanthin and beta-carotene [126]. The neurotoxicity effect
of 1-glutamate was impeded by these carotenoids [127].
10.4 Alga Diterpenes

There is evidence that diterpenes obtained from algae exert antiviral effects
on viruses, including hepatitis virus and HIV among others [128]. Certain
microalgae have been reported to contain phytofurans and phytopros-
tanes, which are derived from alpha linolenic acid. Gracilaria longissima is
such a typical alga. In a report, phytofurans and phytoprostanes extracted
from Gracilaria longissima exerted anti-inflammatory effect in endothelial
cells by inhibiting IL-6 and ICAM levels [129].
The biologic effects of diterpenes have been reported [68]. As at 2017,

about 233 diterpenes were detected in Dictyota spp., the majority of which
came from Dictyota dichotoma. Compound 204, a bicyclic diterpene, was
reported to exhibit anti-inflammatory effects via mechanisms involving
inhibition of nitric oxide production [130].
10.5 Conclusion
Evidence from this study indicates the numerous health-boosting effects of
pharmacological compounds derived from algae. Furthermore, these com-
pounds appear to be more effective and safer in comparison with conven-
tional drugs. Therefore, they are better alternatives to conventional drugs
in the management of diseases.
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11
Application of Algae in Wound Healing
Ebenezer I. O. Ajayi1*, Johnson O. Oladele2 and Abraham O. Nkumah3
1
DC&ONID, Department of Biochemistry, Faculty of Basic and Applied Sciences,
College of Science, Engineering and Technology, Osun State University, Osogbo,
Osun State, Nigeria
2
Biochemistry Unit, Department of Chemical Sciences, Faculty of Sciences,
Kings University, Ode Omu, Osun State, Nigeria
3
Phytochemistry & Phytomedicine (molecular unit), Phytomedicine Research
Group, Department of Pharmacognosy, Faculty of Pharmacy,
University of Ibadan, Ibadan, Nigeria
Abstract
Wounds in living tissues, such as pressure ulcers or chronic skin wounds, pose a
major threat to the healthcare system, especially in the treatment or management
of some pathological conditions, including spinal cord injury, diabetes, etc. Such
wounds have a significant recurrence rate and are only partly successfully treated
with the present medical approaches and technologies. Invasive wound infections
pose a more serious threat to open wounds and can result in amputation and
additional impairment. It takes a multidisciplinary approach to create novel, non-
toxic, noninvasive, and more potent treatments. Thus, there is a growing global
interest in finding natural products that promote skin regeneration. A natural
source of intriguing bioactive chemicals with potential for use in applications for
wound healing is algae. Due to their many biological activities, such as the ability
to inhibit secretion of inflammatory cytokines, antioxidant properties, and anti
microbial activities which are vital in the wound healing process, algae and other
products, including polysaccharides, polyunsaturated fatty acids, and microalgal
carotenoids, may be beneficial in wound management and healing applications.
This chapter presents comprehensive information on wound healing processes,
possible beneficial effects of algae as wound-healing agents, and mechanisms
underpinning the therapeutic wound-healing effects of algae.
251
Keywords: Algae, wound healing, natural products, biomaterials
11.1 Introduction
Wound cicatrization is a dynamic and complex process involving inflam-
mation, proliferation, and remodeling, which are a set of important bio-
chemical and physiological phenomena [1]. Wounds and scarring can arise
from accidents, injuries, hazards, burns, ulcers (such as the diabetic foot
ulcer, Buruli ulcer), lesions (such as the cutaneous leishmaniasis lesions),
bumps, cancer, among many others.
In recent years, algae polysaccharides (PS) have drawn attention for
diverse uses due to their distinct structure similar to the extracellular
matrix of humans, including their biological activity, high biocompatibil-
ity, biodegradability, low toxicity, reproducibility, considerable moisturiz-
ing and swelling ability, and colloidal properties. Algae PS have found a
wide range of applications in regenerative medicine technologies, includ-
ing the composition and technique of wound dressings. Hydrogel-forming
polysaccharides fall into this category, so have other polysaccharide gels,
such as agarose, alginate, carrageenan, ulvan, starch, porphyran, and native
(nano-)cellulose. Natural anionic polysaccharides can also be used, and
their gelation mechanisms make them suitable.
A wide range of wound dressings with many possible applications
have been developed from PS. Impressively clever generation of PS-based
materials for drug delivery systems (DDS), implantable medical devices,
organ and tissue transplant modulation are now developed using the latest
advances in polymer manufacturing technology, including intelligent PS
hydrogels that respond to changes in temperature, pH, pressure, bioelec-
tricity and biomagnetism that promote wound healing [2]. The new inno-
vative approach appreciates the physicochemical and biological properties
required for PS and synthetic polymers. It also offers the opportunity to
employ tissue engineering techniques in reconstructive and transplant sur-
gery. These smart materials can modulate their conformation in the wound
environment without causing biological harm, thus rendering them very
attractive to biosensor monitoring, target-specific molecular recognition,
metabolic control mechanisms, diagnosis, and theranostics, apart from
drug delivery. The purpose of tissue engineering is to grow viable cell pop-
ulations with the desired spatial arrangement by three-dimensional (3D)
bioprinting based on biocompatible materials (combination of different
biopolymers and synthetic polymers) that can contain living cells.
Application of Algae in Wound Healing 253
Three-dimensional bioprinting is a rapidly developing trend in mod-

ern biomedicine used to create viable biological structures in fascinating
and useful spatial configurations. The final product of 3D bioprinting is
implanted in the body and fully dissolves and renovates the host tissue
within a few months. This technology represents an advanced break-
through in the medical field in areas such as reconstruction and transplant
surgery, implantable medical devices, and controlled drug delivery [3]. The
most studied and advantageous compounds that can be used in these sys-
tems are sulfated PS from a wide variety of algae (brown algae alginate and
fucoidan, red algae carrageenan, and ulvans from green algae).
11.1.1 Current Trends in the Design of Wound Dressings

An injury is damage to tissues and/or organs characterized by the destruc-
tion of the integrity of the system (skin and mucous membrane, for instance)
[4]. There is no universal classification system for wounds. However, var-
ious approaches to wound classification (by etiology, localization, type of
damage, depth, degree of complexity, degree of infection, etc.) characterize
wounds to provide their adequate treatment. The following factors are of
greatest importance in the evaluation of wounds: the circumstance (nature
and etiology) of the injury, the time of its occurrence, whether the injury
is acute or chronic, and the depth of damage to the skin and underlying
tissues [5]. Understanding the fundamental mechanisms of wound heal-
ing, as well as knowledge of the type and function of the available dressing
materials, allows a systemic strategy for the choice of dressings to be put
together in the individual patient`s treatment plan. Wound repair or heal-
ing is a complicated process involving multiple overlapping stages that lead
to the repair and restoration of damaged skin anatomy and function [6].
This biological process is highly organized and consists of various forms
of cell renewal such as collagen formation, epithelialization, and tissue
remodeling.
The majority of authors distinguish four stages of wound healing:
hemostasis (exudate coagulation and blood coagulation) which occurs
immediately after injury, inflammation (proteas 1–5 days after trauma,
release of reactive oxygen species (ROS), cytokines, and growth factors,
proliferation (granulation and angiogenesis, days 6–14) and remodeling
(contraction, epithelialization, and scar tissue formation, days 15–16).
Since the inflammatory stage coincides with the hemostasis stage, some
of the authors combine inflammation and hemostasis in the early stages
[7]. Hemostasis, necrotic tissue rejection, wound drainage, tissue nutrition
improvement, and infection control are the goals of Phase 1-2 treatment.
Wound dressings with hemostatic, protective, and absorbent properties are

used to ensure that wound exudate is drained scientifically.
Wound dressings with appropriate agents (anti-inflammatory agents,
antibiotics, preservatives, anesthetics, proteolytic enzymes, and more) are
used to regulate the inflammatory response [8]. The main objectives of pro-
liferative therapy are the protection of granules, the stimulation of repar-
ative processes by growth factors and the prevention of infections. At the
granulation stage, non-traumatic moisturizing dressings containing anti-
biotics can be used. At the remodeling stage, treatment should be aimed at
stimulating the repair process and epithelialization and preventing the for-
mation of hypertrophic, keloid, and atrophic scars. Non-traumatic mois-
turizing dressings, ointments, and gels with low osmotic activity are used
for this purpose. Wound dressings with regenerative properties are used to
stimulate epithelial growth. Bandages that allow delivery of growth factors
and bioactive substances (BAS) are used to promote tissue regeneration
at the site of the local wound. It is also important to adhere to the core
requirements of wound dressings at all stages of treatment. Optimal gas
exchange, moist wound environment, biocompatibility, and avoidance of
allergic reactions, irritation, and burning pain are to be ensured.
There are a wide variety of materials for wound care (healing).
Appropriate wound dressings and patient management plans should be
selected taking into account several factors, including the patient’s general
health, wound complexity and its etiology, and the stage of wound heal-
ing [9]. Except for predominantly closed surgical wounds, a single type
of wound care is rarely used to treat chronic or non-healing open acute
wounds. Complex (with damage to internal organs, large blood vessels,
large nerve stems or bones) and compound wounds (with simultaneous
damage to various organs in several anatomical areas, such as wounds in
the thoracoabdominal region) are complex and need treatment. In this
regard, according to Intisar et al. [10], modern applied wound dressings
must be multifunctional.
Analysis of many studies has made it possible to summarize the basic
requirements for modern wound dressings, viz. adsorption, helps remove
excess wound exudate and related toxic compounds; hemostatic effect as
needed, they are involved in gas exchange and need to ensure high mois-
ture on the wound surface; elasticity and vapor permeability while imper-
meable to microorganisms; insulation, possibility of application without
additional fixation; biocompatibility, they must be sterilized and easily
decomposed after use; they should also be strong and essential, but concise
and cheap.
The use of bio- and synthetic polymers in the form of hydrogels, thin
films (membranes), nanofibers, wafers, foams, and sponges is currently
trending in wound dressing design. Hydrogel coatings are one of the struc-
tural types of wound dressings that deserve special attention. Hydrogels
are a promising biomaterial for biomedical applications. They’ve been used
in a variety of medical applications, including hemostatic wound dress-
ings, drug delivery, tissue engineering, and biosensors. Hydrogel dressings
are believed to have the properties of a complete wound dressing mate-
rial. Hydrogels are 3D structures (scaffolds) made of hydrophilic polymer
chains with corresponding structures and properties. The presence of a 3D
polymer skeleton gives the hydrogel the mechanical properties of a solid,
including lack of fluidity, shape, strength, and the ability to retain proper-
ties such as plasticity and elasticity.
Hydrogels resemble the extracellular matrix of the skin, including col-
lagen and elastin fibers, glucose aminoglycans and proteoglycans, non-
collagen structural proteins, and mineral constituents, allowing them
to perform various functions characteristic of the extracellular matrix.
Because hydrogels are usually transparent, they can be used to monitor
the wound’s condition without having to remove the bandage. The use
of hydrogel dressing helps maintain a moist environment for clean and
healthy granulation tissue, facilitating self-digestive wound resection of
wounds with necrotic tissue such as eschars. Hydrogels can be applied to
pressure ulcers, skin lacerations, surgical wounds, and burns. These dress-
ings are suitable for wounds with minimal to moderate exudate production
[10, 11].
Over the last 15 years, many studies have focused on the development
of topical drug delivery materials using multifunctional compounds that
not only promote stabilization and controlled drug delivery to the target
but also provide biocompatibility. As a drug delivery system (DDS, e.g.,
antibacterial or anti-inflammatory agents, proteolytic enzymes, growth
factors, BAS), hydrogels have received a lot of attention, primarily due to
their highly porous structure and gradual release [11]. Hydrogel-based
DDS includes nano- or micro-sized particles, nanofibers, microspheres,
and microneedles. Nano and microparticles have numerous advantages,
including the ability to deliver drugs via various routes of administration,
the ability to adjust particle size and surface properties, and the ability to
deliver drugs to the desired target in a controlled and long-term manner.
The development of carriers in the form of particulates has created new
opportunities for the development of DDS with improved pharmacoki-
netic and pharmacodynamic properties [8].
Nanofibers have a high surface-area-to-volume ratio and are considered

suitable substrates when highly porous structures are required. Unlike tra-
ditional rigid porous structures, nanofibers are a dynamic system that can
change the size and shape of pores to form flexible or rigid crosslinked
structures. Nanofibers are typically used for drug encapsulation and sus-
tained release, Top of Form as well as in tissue-engineering technologies
such as, in particular, 3D bioprinting [12]. New strategies, such as the use
of new polymer materials that combine the desired physicochemical and
biological properties, represent the current advancements in the advance-
ment of new-generation materials to design wound dressings, DDS, and
implantable structures. Natural biopolymers derived from marine organ-
isms that are biocompatible and biodegradable could be developed using
this method. The most noteworthy of them are algae PS (alginates, fucoid-
ans from brown algae, carrageenans from red algae, and ulvans from green
algae).
11.2 Brown Seaweed Polysaccharides

The brown algae comprising the class Phaeophyceae, are a widespread
group of large algae that abundantly grow in cold seawater at northern
latitudes, although some species grow naturally in freshwater and brackish
water [13]. Brown algae contain fucoxanthin, a carotenoid pigment, which
suppresses other pigments to give plants their characteristic brown color.
Brown algae plants range in size from a few millimeters to about 70 m,
demonstrating a variety of structures and compositions among species
within the same algae class. Large brown algae are composed of complex
and dynamic cell walls rich in polysaccharides such as alginate (also alginic
acid and algin), fucoidan (also fucoidin and fucan), laminarin (also lami-
naran), and cellulose [14], which also contains polyphenols, proteins, gly-
coproteins, phlorotannins (sulfated phenolic compounds), halogens such
as iodine, minerals such as sodium, potassium, calcium, and magnesium
[2]. The relative content of the various compounds varies from species to
species and is highly dependent on seasonal, environmental, and regional
factors. Alginate appears to form a significant portion of all brown algae,
although the laminarin and fucoidan appear to be more common in some
species, such as the genus Laminaria and Fucus spp., than in others [2].
The presence of free sugars such as glucose, fructose, and sucrose in brown
algae is not important as monosaccharides are quickly converted into
D-mannitol polysaccharides [15]. For example, glucose content is seasonal
and primarily binds to beta-glucan laminarin. It acts as an intracellular

storage polysaccharide.
Deniaud-Bouët et al. [16] pointed out that the cell wall of brown algae
is composed of fucose, which in turn contains sulfated polysaccharides
(FCSPs), which are important crosslinked glycans that connect cellulose
microfibrils placed in layers parallel to the cell surface, forming a scaffold
for cells. They went further to mention that short fragments of hemicel-
lulose are intermediates between cellulose and crosslinked FCSP, but the
composition of these proposed hemicellulose fragments are undefined.
These structures are embedded in the alginate matrix. The cell wall matrix
is supposed to be composed primarily of alginate, proteins, polyphenols
(related to these two groups of compounds), and iodine. Mixed-bound
cellulose and/or glucans, which make up a small proportion (<10% DW),
may also play a structural role in the cell wall as microfibrils associated
with fucoidan or alginate [16]. Brown algae seem to have evolved slower
than red algae, green algae, and land plants. No unicellular brown algae
species were found, and the multicellular and plant-like structural evo-
lution of brown algae occurred in isolation from other algae and plants.
However, brown algae share common cell wall polysaccharides with plants
(cellulose), animals (sulfated fucan), and bacteria (alginate) [17]. Although
brown algae contain a wide variety of compounds, most attention and
research has been focused on the use of algal polysaccharides, especially
fucoidan, alginate, and laminarin.
11.2.1 Fucoidan
Fucoidan (Figure 11.1) is classified as a fucose-containing sulfated polysac-
charide (FCSP), which contains polysaccharides of varying chain length,
branched structure, and degrees of sulfation. The main component of
fucoidan is fucose, but it also contains other monomers such as galactose,
mannose, xylose, and glucuronic acid residues [18]. Fucoidan is divided
into two subgroups. The first group has a backbone structure of β-1,3-
rufucopyranose residues, the second group consists of alternating 1,3- and
1,4-linked β-fucopyranose residues from about 40–1600 kDa. Fucoidan
levels appear to be higher in the fall than at any other time of the year
[18]. Fucoidan is thought to be an important component that regulates
the retention of water and ions in the extracellular matrix of plants to pre-
vent drought and osmotic stress during the decline. It is unclear whether
changes in composition correlate only with increased storage polysaccha-
rides or whether changes also affect the structure of plant tissue [19].
H3C
O OH
H 3C
HO3SO O
OSO3H
O
OSO3H
O
Figure 11.1 Fucoidan [20].
11.2.2 Alginate
Alginate (Figure 11.2) is a salt of alginic acid, a linear non-branched copo-
lymer composed of 1,4-domanneuronic acid (M) and 1,4-I-glucuronic
acid (G). Copolymer size, M/G ratio, and integrated G-block properties
affect compound function, physical properties, mechanical strength, and
biocompatibility [21]. The M/G ratio of alginate depends on the species
of algae, the time of harvest, and the structure and age of the algae tissue.
The chelating properties of alginate depend on the length of the G block
of the compound (repetitive structure of glucuronic acid) [22]. Due to the
rheological properties of alginate, these polysaccharides are widely used
in industries such as pharmaceuticals, medical devices, cosmetics, food,
agriculture, textiles, and papermaking [22]. Alginate is used industrially
primarily for physical properties such as stabilization, thickening, emulsi-
fication, etc., but tissue engineering depends on specific properties such as
gel strength, porosity, biocompatibility, etc. It is expanding to applications
such as biomaterials for bioprinting and biofabrication. Alginate is an ana-
log of land plant pectin [23]. It is extracted from brown seaweed and is clas-
sified as a phycocolloid, a polysaccharide that can form a colloidal system
H
COO- H
O
H
H H O OH
OH OH O
O H H O
H H
COONa n
Figure 11.2 Alginate [26].

when dispersed in water. Alginate is formed when alginic acid interacts

with the metal ions, such as calcium, sodium, and magnesium, in which
it is present. Calcium alginate forms water-insoluble gels, and sodium and
magnesium salts of alginate form water-soluble gels [24]. Glycosidic bonds
between the sugar monomers of alginate polymers can cleave under both
acidic and alkaline conditions, leading to compound degradation. Other
factors that affect the stability of the copolymer are temperature and free
radicals produced by impurities such as polyphenols [25].
11.2.3 Carrageenan
Carrageenan (Figure 11.3) is a high molecular weight sulfated polysaccha-
ride present in the cell wall of red algae that interacts with other bioactive
compounds such as proteins, lipids, pigments, and other polysaccharides.
It is composed of alternating 1,3-linked d-galactopyranosyl and 1,4-linked
d-galactopyranosyl groups and 3,6-anhydrogalactose residues. The three
major commercial types of carrageenan are kappa, iota, and lambda car-
rageenan, which differ in the amount and location of sulfate group groups
and the number of 3,6-anhydrogalactose residues. Carrageenan is com-
posed of 25–30% sulfate ester groups and 28–35% anhydrogalactose. The
sulfate ester content of carrageenan is similar to the sulfate ester content of
carrageenan (28–30%), but with a lower percentage of anhydrous galactose
units (25–30%). Carrageenan sulfate substitutions are relatively high (32–
39%) but do not contain anhydrous galactose residues [27]. The backbone
can be substituted by pyruvate ketal, which is only reported for the family
of carrageenans [28].
The composition of carrageenan varies between species. For example,
carrageenan from Kappaphycus alvarezii (in the trade also called Eucheuma
cottonii) is made up of the main carrageenan, whereas Eucheuma denticu-
lated (trade name Eucheuma spinosum) consists of carrageenan. Chondrus
crispus and Sarcothalia crispata contain both carrageenan. The water solubility
HO3SO
OH
O
O
O O
O
* *
OH
OH n
Figure 11.3 Carrageenan [32].

and gelation of carrageenan depend on the amount of sulfate ester groups

and associated divalent cations, such as sodium and potassium, although
carrageenan can form a gel in the presence of trivalent ions [27]. A large
number of sulfate ester groups lowers the temperature required for solu-
bility, lowers gel strength, and affects the application of carrageenan [29].
Details on the origin, structure, and properties of carrageenan are pro-
vided in a comprehensive review by Campo et al. [30] and Sharma et al.
[31].
11.2.4 Red Seaweed Polysaccharides

The red alga, Rhodophyta, is a group of predominantly multicellular photo
synthetic eukaryotes reported to contain more than 7,000 species. They
grow primarily in marine habitats, but up to 5% of species grow in fresh-
water environments and can grow more in warmer regions. The red color
is represented by the predominance of the pigments phycocyanin and phy-
coerythrin over other pigments such as chlorophyll A and carotene. Red
algae store sugar as active starch, an amylose-free, highly branched amylo-
pectin that accumulates outside the plastids of the cytosol of cells [28]. The
cell wall of algae is mainly composed of cellulose, carrageenan, and agar, all
of which have multiple industrial uses.
11.2.5 Green Seaweed Polysaccharides

Green seaweeds are members of the Chlorophyta phylum, which include
the majority of the described species of green algae [33]. Chlorophytes can
be found in both marine and freshwater environments. Marine macroalgae
(the focus in this review) from the classes of Chlorophyta in principle
involve the class Ulvophyceae [34] and mainly include candidates from the
orders Ulvales, Ulotrichales, Cladophorales, and Bryopsidales, including
species that display large morphological and cellular diversity [34]. Ulva,
Gayralia, and Monostroma (classified under the order Ulvales, Ulotrichales),
Cladophora (Cladophorales), Caulerpa, and Codium (Bryopsidales) are all
well-known genera classified under Ulvophyceae, and have all been used
in human diets in various parts of the world. Despite their indigenous
and long history of use, green seaweeds are less well studied than red and
brown algae, and while they have potential, they lack the major industrial
applications that red and brown algae have. Green algae contain interest-
ing polysaccharides that are sulfated and/or carboxylated. The skeletons of
the major polysaccharides, found in candidate species of different genera,
can be broadly divided into two major groups, uronic acid-rich or uronic
acid-restricted [34].
Sea lettuce is found in various types of Monostroma. The composition of
sea lettuce has been reported to be dependent on species, season, growth
conditions, and method of separation [35]. Four different types of mono-
saccharides (rhamnose (Rha), xylose (Xyl), glucuronic acid (GlcA), and
iduronic acid (IdoA)) have been described along with different types of
Orban sulfate groups. All four monosaccharides can be present in the skel-
eton, but only glucuronic acid is present [36]. In the side chain, uronic acid
can either be glucuronic acid or iduronic acid, and it is often reported to
be composed of “Rha uronic acid” [35]. Uronic acid-restricted polysac-
charides are found, for example, in Codium species and are described as
sulfated galactan, arabinopyranan, and mannan.
11.3 Mechanisms Underpinning the Wound Healing

Effects of Algae
Several investigations have been undertaken on algae targets and their
wound healing mechanisms. Wound healing is a complex, dynamic, and
precisely programmed process that involves various interactions between
physiological, biochemical, molecular, and cellular activities. Wound
healing occurs in four stages, which include remodeling, proliferation,
inflammation, and hemostasis, with the goal of restoring the physiological,
functional, and structural integrities of injured tissues [37]. This procedure
results in the replacement and regeneration of injured tissue at the site of
the wound [38]. A variety of natural products and nutrients are required
for proper collagen formation, immune function, and cellular differenti-
ation [39]. Any deviation, interference, or postponement in the healing
process would intensify tissue damage and thus prolong the repair pro-
cess, contributing to chronic wound healing [40]. In recent times, there
has been an increase in the supply of various wound dressings, each with
unique properties that take into account the unique healing requirements
of various wound types. Various natural and synthetic products have been
extensively researched for their efficacy and ability to accelerate wound
healing in order to meet the need for appropriate dressing for a specific
wound type.
Synthetic products are unsuitable for healing because they are nonab-
sorbent and nonbiodegradable [41]. Medicinal plants are being studied
extensively for their use in wound healing, and the ancient knowledge of
medicinally important plants, as well as their increased popularity and

utility, has fueled interest in discovering new natural products useful in
the healing process. Several studies have confirmed the antibacterial, anti-
oxidant, pro-collagen synthesis, and anti-inflammatory activities of nat-
ural products derived from plants and microbes [42, 43], which could be
beneficial for healing. The existence and biocompatibility of numerous
biologically active compounds in natural products effectively enhance the
healing process and make them financially usable for designing and manu-
facturing wound dressings [44]. Researchers are screening organisms from
overlooked microbial sources with the potential to be used as effective
wound healing agents, such as algae (e.g., Cyanobacteria), Bacteroidetes,
and Proteobacteria. Their efforts are geared towards meeting the demand
for new natural therapeutic agents for wound healing while lowering the
average costs involved in their development.
Algae, for instance Cyanobacteria, are oxygenic photosynthetic bacteria
found in a variety of forms such as filamentous and unicellular, freshwater
or marine, edible, free-living symbiotic, and poisonous [45, 46]. This group
of organisms has the ability to produce a large number of primary and
secondary metabolites, and as a result, they are known to have substan-
tial biological activities. These synthesized secondary metabolites are low
molecular weight natural organic compounds that are required for nor-
mal growth and development of these organisms. These metabolites have
a diverse range of applications in biotechnology, industry, and medicine.
They are also rich sources of bioactive compounds, with cyanobacteria
being the most promising producers. Cyanobacteria have received a lot
of attention in recent decades for their medicinal and wound-healing
properties.
They are the organisms of choice due to their vast diversity, rapid regen-
eration, and ease of availability, which has piqued the interest of research-
ers for their potential as functional foods and medicine [47]. As a result,
their propensity as a novel natural therapeutic drug candidate has been
recognized. Secondary metabolites from cyanobacteria have a variety of
medicinally important activities, including protease inhibition, immuno-
modulatory, anti-inflammatory, antiviral, antifungal, antibacterial, and
antitumor [48]. These biological activities aid in wound healing in a vari-
ety of ways. Despite their prevailing biological activities, very few algae are
known to aid in wound healing. Thus, this section provides an overview
of bioactive compounds in algae that are responsible for their various bio-
logical activities that promote wound healing by influencing its different
phases and factors.
11.3.1 Hemostatic Activity

Traumatic injuries have been a source of frustration for people all over
the world. Despite technological advancements, trauma remains a lead-
ing cause of human morbidity and mortality [49]. Excessive bleeding can
result in delayed wound healing, necrosis, dehiscence, infection, and the
formation of hematomas. Patients suffering from trauma and subsequent
hemorrhage necessitate the application of topical wound dressings to
achieve hemostasis. Hemostasis requires the formation of blood clots, acti-
vation of the coagulation cascade, and the constriction of blood vessels. As
a result, any effort to accelerate any or all of the above phases can aid in the
achievement of hemostasis [50].
The role of algae and cyanobacteria in hemostasis is far less well under-
stood and recognized. The majority of them have antithrombic functions
that can be used to treat thrombosis-related diseases. Spirulan, a sulfated
polysaccharide derived from Arthrospira platensis, is well known for its
antithrombic activity. Spirulan could be used to prevent thrombus forma-
tion and partial thrombus lysis by directly decreasing the activity of throm-
bin and factor X activated procoagulant proteins [51]. Similarly, Microcystis
aeruginosa and various cyanobacteria blooms produce fVIIa-soluble Tissue
Factor (fVIIa-sTF) inhibitors [51]. Bleeding, related complications, and
disorders are linked to vitamin-K-dependent clotting factors like thrombin
and fVIIa. When combined with vitamin-K antagonists, these factors can
cause excessive bleeding. M. aeruginosa produces aeruginosin, a bioactive
compound with fVIIa-sTF inhibitory activity. When tested on humans for
anticoagulant activity and platelet activation ability, daily consumption of
an aqueous extract of Spirulina platensis containing a high dose of phyco-
cyanin was found to be safe. The investigated extract is also suitable for
providing rapid and effective pain relief in chronic pain. The extract also
improved liver function and metabolism by inhibiting the activity of ala-
nine transaminase and aspartate transaminase [52].
C-phycocyanins derived from Spirulina platensis have DNA damage
prevention, antioxidant, and anticoagulant properties [53]. A. platensis
exopolysaccharides have antiatherogenic and antithrombogenic properties
[54]. Although the important roles of cyanobacterial and algal polysaccha-
rides as anticoagulants, antitumoral, antivirals, and antioxidants have been
well documented [48], only one report to date has mentioned the role of
cyanobacterial exopolymers (EPs) isolated from four desert cyanobacte-
ria (Tolypothrix tenuis and three Anabaena species) in hemostasis. These
exopolymers had the potential to reduce activated partial thromboplastin
time (aPTT, a measure of the length of time it takes for clotting to occur
when reagents are added to plasma in a test tube) and prothrombin time
(PT, a measure of how long it takes for a clot to form in a blood sample) by
16–41% and 12–65%, respectively.
The gravimetric thrombogenicity test revealed that the blood clot formed
by the cyanobacterial EPs was heavier than glass (the positive control), and
thus is thrombogenic. Similar research can uncover the untapped potential
of cyanobacterial bioactive compounds in hemostasis, which needs to be
explored further.
11.3.2 Immunomodulatory and Anti-Inflammatory Effects

Inflammation is a defensive, localized response to microbial invasion or
injury. The magnitude of the inflammatory response is critical: excessive
responses lead to morbidity and mortality, whereas insufficient responses
lead to immunodeficiency. As a result, when inflammation is limited by
anti-inflammatory responses, homeostasis and health are restored [55].
Natural compounds have received a lot of attention in the treatment of
various types of inflammations in order to reduce the immune system’s
reaction to pathogens, toxic compounds, and damaged cells.
The immune system actively participates in homeostasis, re-
establishment, and wound healing via multiple mechanisms, and plays an
important role throughout the wound-healing process. When developing
regenerative strategies, using immune system control to promote tissue
repair and regeneration is an appealing approach. Algae’s multifunctional
immunomodulatory properties are receiving a lot of attention in the med-
ical field these days. Algae produce a variety of metabolites with vary-
ing chemical structures, including proteins, fatty acids, polysaccharides,
small molecules of peptides, and their derivatives, all of which have anti-
inflammatory properties [56]. Various algae’s components regulate the
release of specific cytokines from human monocytes and macrophages.
They can also reduce or activate the secretion of reactive oxygen species
by neutrophils, depending on the wound microenvironment [57]. Algae’s
immunomodulatory effects strongly mediate activation of both types of
immune cells, which may promote wound closure, accelerate re-epitheliza-
tion, and wound debridement [58].
Marine algae are a potential source of anti-inflammatory agents by
mediating various factors involved in the inflammation process. Several
significant phycocompounds found in marine algae, such as carbohy-
drates, lipids, fatty acids, fucoxanthin, flavonoids, terpenoids, their deriv-
atives, polyphenolic compounds, and amino acids, are involved in the
inflammatory response. The significance of seaweed and its potential role
as a source of anti-inflammatory substances were examined [58, 59]. The

aqueous extract of the marine brown alga Turbinaria ornata (Turner) J.
Agardh also showed anti-inflammatory activities and the ability to scav-
enge free radicals [60]. The brown seaweed, Laminaria japonica, in its own
right, had significant anti-inflammatory and antidiabetic effects in a high-
fat diet-induced obese mouse. The study demonstrated the use of seaweed
for a variety of health benefits [61]. By studying their antiadhesive, anti-
angiogenic, anticoagulant, and anti-inflammatory activities, Fucus vesic-
ulosus, F. distichus, F. serratus, L. digitata, and Laminaria saccharina were
found to have a strong effect in tumor metastasis [62].
Purified components sulfated polysaccharide fractions from Sargassum
wightii and Halophila ovalis were tested for antinociceptive and anti-
inflammatory effects in male Wistar rats [63]. The potential applicability
in the industrial formation of Ecklonia cava (Laminariales) and Sargassum
horneri (Fucales) was found to be in the 8:2 ratio, and both algae suppressed
lipopolysaccharide-induced inflammation by preventing the NF-kB and
MAPK pathways [64].
Polyphenol is an important phyco-component that has been linked
to antioxidant and anti-inflammatory responses. The antioxidant and
anti-inflammatory activities of the polyphenol-rich fraction of Sargassum
muticum was non-cytotoxic, whereas it inhibited cellular ROS genera-
tion, protected Vero cells, as well as UV-B-irradiated HaCaT cells against
H2O2 and AAPH induction [65]. Similarly, marine algal biomaterials may
have important biological effects such as anti-inflammatory, antioxidative,
and anticancer properties [66].
The medicinal value of red seaweed Dichotomaria obtusata is found to
be a promising treatment of peripheral pain and/or inflammatory condi-
tions that have been screened using various tests such as analgesic activity,
mouse-ear edema test, and writhing test [67]. Radhika et al. [68] investi-
gated the anti-inflammatory properties of four seaweeds: Padina tetrastro-
matica, Sargassum wightii, Gracilaria edulis, and Caulerpa racemose. They
discovered that carrageenan has anti-inflammatory properties. Similarly,
the significant anti-inflammatory activity of methanol extract of Gracilaria
corticata J.Agardh (Red Seaweed) was investigated. The highest percent-
age (95.55%) of anti-inflammatory activity in G. edulis aqueous extracts
was 250 g/ml, whereas the lowest was found in G. corticate var. cylindrica
(Tuticorin) [69]. On the other hand, the bioactive compounds of the
green seaweed, Ulva prolifera from fish pond aquaculture, showed anti-
inflammatory activity and was bioaccessible [70].
Edible forms of algae are well-known for their immune-boosting proper-
ties, and numerous studies have revealed that they have anti-inflammatory
and immunomodulatory properties. Spirulina is a popular alga (cyano-

bacterial strain) due to its exceptional pharmaceutical and nutraceutical
properties. Spirulina platensis dietary effects increased antigen and phago-
cytic production, and the natural killer cell-facilitated anticancer property
in laboratory animals [71, 70]. Spirulina consumption on a daily basis
stimulates and promotes the immune system by activating T and B cells,
increasing natural killer cell accumulation in tissues, inducing antibodies
and cytokines production, and increasing macrophage phagocytic activity
[72].
In humans, daily consumption of spirulina for 16 weeks resulted in a
marked elevation of plasma IL-2 concentration and a marked decrease in
IL-6 concentration [73]. Nonadecane and 9-eicosyne have been reported to
be responsible for the anti-inflammatory effects of spirulina [74]. Immulina®
is a high-molecular-weight polysaccharide extracted from Spirulina that is
a potent inhibitor of the induced allergic inflammatory response and acti-
vator of innate immune cells [75, 76]. It also has anti-inflammatory prop-
erties and can inhibit histamine release from mast cells [75, 77]. The fatty
substances are extracted from Spirulina and Aphanizomenon flos-aquae,
respectively, that inhibit the formation of inflammatory mediators are
known as gamma and alpha-linolenic acid [78]. Nostoc, like Spirulina, is an
edible, widely consumed algae form that is used to treat human monoblas-
tic leukemia U937 cells. Polysaccharide-rich extracts of Nostoc commune
could potentially be used for macrophage activation, inhibiting leukemic
cell growth and inducing monocytes/macrophages [79].
Different immunomodulating activities of Oscillatoria tenuis, Oscill
atoria rubescens, Aphanizomenon flos-aquae, Anabaena flos-aquae, Oscill
atoria redekei, Synechocystis aquatilis, and Microcystis aeruginosa have
also been documented [80], which have different cell extracts that vari-
ably promote the proliferation of lymphocytes. Some algae species, on the
other hand, comprise cytotoxic metabolites (cyanotoxins) that can induce
immunosuppression and immunotoxicity. Immunotoxicity has been well
documented in cyanobacterial bloom extracts containing microcystin
[81]. Microcystin inhibited lipopolysaccharide-induced lymphoprolifer-
ation and decreased the number of antibody-forming cells, resulting in
immunosuppression in mice immunized with T-dependent antigen sheep
red blood cells. Cylindrospermopsin, a type of algae toxin, is a significant
water pollutant with broad biological activity. When introduced into mac-
rophage cells, cylindrospermopsin promotes significant production of the
pro-inflammatory mediators such as tumor necrosis factor alpha and reac-
tive oxygen species [82].
Aqueous extracts of different algae species including, Oscillatoria tenuis,

Oscillatoria rubescens, Aphanizomenon flos-aquae, Anabaena flos-aquae,
Oscillatoria redekei, Synechocystis aquatilis, and Microcystis aeruginosa,
possess strong immunomodulating activities [83]. Anti-inflammatory
activity is demonstrated by aqueous extracts of the marine cyanobacte-
rium Trichodesmium erythraeum and ethyl acetate extracts of the non-
edible blue-green algae Geitlerinema splendidum [83, 84]. In chronic
wounds where a coordinated wound-healing cascade fails to progress
beyond the inflammatory phase, cyanobacteria’s anti-inflammatory activ-
ity aids wound healing through proliferation, matrix deposition, and,
eventually, wound resolution [85]. Several bioactive compounds with anti-
inflammatory properties have been isolated from algae, indicating their
importance and potential in developing a large market of wound-healing
aids [86]. Terpenoids, steroids, polysaccharides, phenols, and phycobilin
are examples of algae’s bioactive compounds that have anti-inflammatory
properties.
11.3.3 Antioxidant Activity

Antioxidants are substances that protect the body from oxidation. They
counteract oxidative stress by removing free radicals and allowing tis-
sue regeneration by repairing cells [87]. During wound healing, respira-
tory burst produces oxidants; the production of these oxidants aids in the
acceleration of healing. These produced oxidants act as messengers, pro-
moting healing. However, a delicate balance of oxidants and antioxidants
is required to control the wound’s progression. Low physiology levels of
reactive oxygen species and oxidative stress are required at wound sites for
normal wounds. Whereas their overexposure cause oxidative stress and
impair wound healing.
Increased levels of antioxidants are expected to improve the level of oxi-
dative stress, which will aid in the acceleration of healing [88]. Antioxidants
also protect and stimulate immune cell function against homeostatic dis-
orders. As a result, their increased levels can improve immune response
and hasten wound healing [89]. Overabundance of low molecular weight
iron at the wound site also enhances microbial invasion and inflammation
[90], implying that a chelating agent is required to achieve proper heal-
ing. The generation of various, chemically diverse groups of secondary
metabolites from algae established their immense applications and made
them an excellent source of antioxidants that enhance the establishment of
the body’s defense mechanism against free-radical-mediated cell damage.
Their cell-free extracts have metal chelating, deoxyribose protection and
free radical scavenging properties [48]. These antioxidant and metal che-
lating properties are attributed to the phytonutrients and pigments found
in them [91].
The antioxidant properties of algae extracts are provided by the total
flavonoids and phenolic content of the extracts. Kaempferol, quercetin,
flavonoids, ferulic acids, vanillic, caffeic, chlorogenic, gallic, and other
polyphenols found in algae extracts are thought to be responsible for their
antioxidative damage protection, metal chelating, and free radical scav-
enging properties. Algae (cyanobacteria) exopolysaccharides also have
antioxidant and anticoagulant properties. They can induce antioxidant
enzymes, as well as act as immunostimulants [92]. Exopolymers of three
strains of Tolypothrix tenuis and Anabaena exhibited antioxidant activi-
ties against nitric oxide radicals, hydroxyl radical, hydrogen peroxide, and
superoxide radicals, thus help in the rapid healing of the wound [94]. These
polymers also have iron chelating property, which aids in the prevention
of pathogenic organisms from invading the wound site. There was a strong
correlation between sulfate content and superoxide and nitric oxide radical
scavenging activity of exopolymers, whereas phenols contributed to their
hydrogen peroxide scavenging ability and free radical reducing power.
Their overall superoxide suppression and free radical reducing power are
strongly related to their ability to chelate iron [94].
Lyngbya sp. had the highest phycobiliprotein, flavonoid, and pheno-
lic content, as well as the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH)
activity. The antioxidant potential of Spirulina sp. was thought to be related
to the presence of alcoholic and phenolic OH groups in the organism’s cel-
lular structure [91]. Ethanol extracts of Phormidium fragile, Lyngbya lim-
netica, Scytonema bohnerii and Calothrix fusca possess antioxidant ability
[94]. Similarly, methanol extracts of Arthrospira platensis, Phormidiochaete
sp., Leptolyngbya protospira, Nodularia spumigena, Nostoc commune,
Nostoc sp., and Anabaena sp. have been documented to have higher phe-
nolic content and antioxidant activity than their aqueous extracts [93].
Antioxidant properties are also found in cyanobacterial pigments. The
ability of Lyngbya and Phormidium sp. to scavenge peroxyl and hydroxyl
radicals has been linked to the presence of a covalently linked tetrapyrrole
chromophore with phycocyanobilin [95]. Phycocyanin, a phycobiliprotein
isolated from Spirulina platensis and Geitlerinema sp., has been shown to
have antioxidant and anti-inflammatory properties, as well as the ability to
scavenge superoxide, hydroxyl, and peroxyl radicals [96]. Cyanobacteria
polysaccharides, pigments, and phytonutrients have strong anticoagulant,
antioxidant, and metal chelating activities [91, 92].
11.3.4 Antifungal Activity

Detrimental chronic wound infection is a major cause of trauma world-
wide, causing serious public health issues. Infections in wounds are pri-
marily caused by bacteria, but very few recent studies have examined both
fungal and bacterial communities in the microbiome of chronic wounds,
indicating the role of fungi as underappreciated agents that lead to compli-
cations at the wound site [97].
Members of the genus Candida are primarily responsible for the infec-
tion of difficult-to-heal wounds such as diabetic foot ulcers (DFUs) [98].
Prolonged infection combined with delayed healing, makes these wounds
chronic and difficult to manage. Diabetic foot ulcers isolated more than 75%
of the Candida species. In diabetic foot ulcers, respiratory disease, and aller-
gic rhinitis, allergic fungi such as Fusarium spp., Pleospora spp., Alternaria
spp., Penicillium spp., Aspergillus spp., and Cladosporium spp., are docu-
mented as life-threatening infection-causing organisms. Opportunistic
and pathogenic fungi, including Rhodotorula spp., Trichosporon asahii,
and Candida spp., have been documented to be linked with stalled open
wounds or wounds resulting in an amputation [97].
Antifungal drugs are limited in their ability to treat infected wounds due
to their adverse side effects and high cost. As a result, there is a growing
need to discover a new natural fungicidal agent. Many compounds isolated
from algae have been documented to have inhibitory effects against vari-
ous pathogenic fungi strains [93]. They are rich sources of bioactive com-
pounds from a variety of chemical classes, including peptides, polyketides,
and alkaloids [100]. Bioactive antifungal compounds like hapalindole, fish-
erellin, phytoalexin, tolytoxin, scytophycin, carazostatin, nostocyclamide,
and nostodione are isolated from different strains of algae [101]. Organic
extracts of several algae, like Microcystis aeruginosa, Aphanothece bullosa,
Lyngbya aestuarii, Lyngbya martensiana, Phormidium corium, Chroococcus
minor, and Oscillatoria laetivirens, have potential antifungal activity against
Aspergillus flavus and Candida albicans [102].
11.3.5 Antibacterial Properties

In response to various environmental stresses, seaweeds or marine algae
produce metabolites, which can be used as an antimicrobial component
against viruses, protozoa, fungi, and bacteria. Many researchers used
different types of solvent extracts to screen many marine algae for anti
microbial compounds and antimicrobial activities from various sea coasts
[103]. Among all of them, marine algae are known to produce bioactive
compounds such as primary and secondary metabolites, making them a

rich source of metabolites. The efficacy of various algae-derived compo-
nents, their mode of action, and applications as antibiotics, disinfectants,
and inhibitors of food pathogens and spoilage bacteria, among other
things, have been documented [104].
Antibacterial compounds are molecules that suppress or inhibit bacte-
rial growth by interfering with their physiological processes. Temperature
increase induced by immune response inflammation and humidity due to
fluid accumulation at the wound surface make wounds more highly sus-
ceptible to bacterial infections. Bacteria can penetrate underlying tissues
and cause life-threatening infections if they come into contact with the
wounded site. Advanced wound management techniques are important
for dealing with such pathological conditions.
To improve the healing process and reduce wound bacterial colonization
as well as infection at the wound site, systematic antibiotics and the use of
antimicrobial-loaded wound dressings are viable options for overcoming
infection and the associated delay in healing. Because the use of antibiot-
ics has resulted in the emergence of multidrug-resistant (MDR) strains of
bacteria, which has a negative impact on the healing process and worsens
the problem [104], there is a need to develop/discover an effective wound
management material capable of curing wounds in such conditions. Several
cyanobacteria have been found to produce antibacterial intracellular and
extracellular bioactive compounds [105]. These natural products are active
against a wide range of bacterial strains like Bacillus cereus, Streptococcus
pyogenes, Mycobacterium smegmatis, Serratia marcescens, Pseudomonas
aeruginosa, Bacillus subtilis, Micrococcus flavus, Staphylococcus albus,
Salmonella typhi, Staphylococcus aureus, Escherichia coli, Staphylococcus
epidermidis, and some other Gram-positive and Gram-negative bacteria
[102, 106–109]. Nevertheless, making antibacterial agents is dependent on
some criteria such as light intensity, temperature, pH, incubation period,
and the conformation of the culture medium during the growth of algae
[110].
The antimicrobial activities of compounds derived from various marine
seaweeds that have been documented [111] showed that phlorotannins
have antimicrobial properties. Compounds from marine natural products
have significant applications in the pharmaceutical industry. These include
polysaccharides, fatty acids, phlorotannins, pigments, lectins, alkaloids,
terpenes, and halogenated compounds derived from algae [112]. Seaweed
produces metabolites that help protect against various environmental
stresses [113]. The antimicrobial activity of two marine algae, Gelidium
sesquipedale and Laminaria ochroleuca, was investigated. The methanolic
extract of selected algae was found to have a significant antimicrobial

action on selected bacterial test strains. The authors went further to inves-
tigate the antimicrobial activity of red algae extracts Ceramium rubrum
(Rhodophyta), Sargassum vulgare, Sargassum fusiforme, and Padina pavon-
ica (Phaeophyta) against multidrug-resistant bacteria, and observed that
the presence of phyco-compounds such as phenols, terpenes, indoles, fatty
acids, and volatile hydrocarbons warrants such activity.
The methanol extract of the marine brown alga Spatoglossum asperum
had highly effective antibacterial activity (84.94%) against a variety of bac-
terial pathogens [114]. In-vitro antimicrobial activity of solvent extracts of
the marine brown alga Hydroclathrus clathratus (C. Agardh) against human
bacterial and fungal pathogens was evaluated by Vimala and Poonghuzhali
[115]. Sargassum swartzii, Jania rubens, and Stoechospermum margin-
atum were discovered to have a broad spectrum of antibacterial activity
against all of the pathogens tested [116]. Ulva fasciata, Gracilaria corticata,
Sargassum wightii, and Padina tetrastromatica had significantly higher
activity against 70% of isolated bacterial test cultures, and were generally
higher in Gram-negative bacteria [117].
11.3.6 Wound-Healing Property of Algae and Cyanobacteria

Specific wound healing requirements broaden the scope of characterizing
more natural, cost-effective, and effective wound-healing agents, resulting
in the extraordinary rise of many synthetic and natural products useful as
suitable wound-healing dressing materials. Plant-derived natural products
are well-known for their medicinal properties, which aid in wound heal-
ing. Plant-based natural products contain bioactive secondary metabolites
such as phenolics, saponins, terpenoids, tannins, flavonoids, essential oils,
and alkaloids [118, 119]. These compounds have procollagen synthesis,
antibacterial, antioxidant, anti-inflammatory, and other activities [120], as
well as the ability to modulate one or more phases of the wound-healing
process, which aids in increasingly rapid tissue regeneration during heal-
ing [121]. Likewise, algae and cyanobacterial bioactive compounds have
important medicinal properties, such as anticancer, antialgal, antifungal,
antibacterial, antioxidant, antiviral, and immunostimulant activity [121,
122], but only a few are known to have wound-healing potential.
Methanolic extract of the brown algae Sargassum wightii, for example,
has significant anti-inflammatory, antipyretic, and wound-healing prop-
erties [123]. According to Madkour et al., the blue-green algae may have
a potential biological property which could be beneficial in the treatment
of various chronic wounds, particularly in patients with diabetes mellitus.
They investigated sample extracts on human dermal fibroblast cells (HDF)

using an in-vitro scratch assay. A selected experimental medicinal extract
mixture was effective for wound-healing intervention in the diabetic rat
model. The beneficial extract encouraged wound contraction, decreased
wound closure time, and stimulated fibroblast proliferation, as well as
angiogenesis and re-epithelialization. They further reported the poten-
tial wound-healing and hepatoprotective properties of Gracillaria crassa,
whereas Laurencia papillosa demonstrated antiulcer activity for future
pharmaceutical applications [124]. The investigation of aqueous extracts
from 23 different seaweed species extracts suggested that they could be
a potent pharmacological agent for skin wound-healing activity via vari-
ous mechanisms [125]. In contrast, an effective positive effect of spirulina
crude protein (SPCP) on the viability of human dermal fibroblast cell line
(CCD-986sk cells) was investigated [126].
Spirulina, often referred to as blue-green microalgae, has been extensively
studied for its wound-healing potential, as well as its blood lipid-lowering,
blood vessel relaxing, hepatoprotective, immune-enhancing, antiallergic,
anticancer, antiviral, antimutagenic, and antioxidant properties [127, 128].
C-phycocyanin isolated from Spirulina’s pigment stimulated cell migra-
tion, regeneration, and proliferation in human keratinocyte cultures. A
similar set of experiments on Sprague-Dawley male rats revealed matu-
ration, tissue granulation amount, inflammatory cell presence, neovascu-
larization, and re-epithelization during wound healing [129]. When tested
on human dermal fibroblast cells (HDF), an aqueous extract of Spirulina
platensis showed an increased rate of wound closure migration and prolif-
eration within 24 hours. Phosphatidylserine, cinnamic acid, temsirolimus,
kaempferol, narigenin, and isomeric derivatives were presumably involved
in the accelerated wound-healing activity of the Spirulina platensis aque-
ous extract studied.
Spirulina’s antioxidant and antibacterial properties can help improve
skin cell immunity, so a burn cream containing an ethanol extract of
Spirulina and gold nanoparticles has been developed. Lidocaine as an anes-
thetic, sodium dodecyl sulfate, and glycerin for skin moisturization have
been added to the cream to reduce pain by numbing the injured area [130]
Polyhydroxybutyrate (PHB) polyethylene oxide, and polylactic acid (PLA)
were extracted from the Arthrospira LEB 18 strain and used to create bio-
compatible, biodegradable nanofibrous scaffolds. Increased conductivity,
higher mechanical durability with enhanced elasticity, tensile strength, and
breaking elongation of prepared scaffolds supported nutrient, growth fac-
tor, and metabolism byproduct distribution at the wound site [131].
When compared to classic poly-D,L-lactic acid (PDLLA), scaffolds

of PDLLA associated with LEB 18 biomass increased cell viability, and
demonstrated better wound adherence with more moldability [132]. Such
biomatrices derived from Arthrospira can promote natural wound-healing
processes while also lowering the risk of infection [133]. As a cutaneous
wound dressing material, a PCL nanofiber loaded with Spirulina extract
was created. The designed dressing improved wound regeneration by mod-
ulating intra- and extracellular ROS, increasing fibroblast viability under
oxidative stress, and enhancing the antioxidant mechanism. In mice,
Synechococcus elongatus, a naturally occurring photoautotrophic cyano-
bacterium, promoted angiogenesis and burn wound repair. The stimula-
tion of interleukin-6 expression and extracellular vesicle secretion most
likely induced pro-angiogenic and wound-healing effects in the animals
studied [132].
UV-absorbing mycosporine-like amino acids (MAAs) are secondary
metabolites found in a variety of marine, freshwater, and terrestrial organ-
isms. Nostoc flagelliforme and Nostoc commune are well-known for their
edible qualities and have been reported as MAA natural resources. These
secondary metabolites have a variety of beneficial effects and can be used in
sun-screening cosmetics, antioxidants, and pharmaceuticals [133]. MAAs
modulate skin fibroblast proliferation and activate adhesion kinases, which
are extracellular signal-regulated kinases that promote wound healing.
Comprehensive research is being conducted on MAAs to determine their
potential as a new wound-healing agent to be investigated as a novel bio-
material for wound-healing therapies [134].
Cyanobacterial glycans are hydrogels that absorb large quantities of
biofluids [135]. This property of glycans makes them extremely useful for
targeted drug delivery in chronic wound cases [136], where they have been
used to deliver low molecular weight drugs as well as macromolecular pay-
loads (hormones, peptides, and protein drugs) [137]. Cyanobacteria have
been extensively researched and studied for their enormous potential in
a variety of biomedical applications, but only a few have been reported
to have accelerated wound-healing abilities. The majority of the research
has focused on Spirulina, which is well-known for its extraordinary nutra-
ceutical and pharmaceutical properties. Because these organisms are
phototrophic and have minimal growth requirements, they can be easily
regenerated, and their enormous diversity makes them suitable research
candidates with hidden potential for wound healing. They can also be used
to create bioactive and cost-effective wound-dressing materials for people
from all walks of life.
11.4 Conclusion
Polysaccharides have a lot of structural variation depending on algae spe-
cies, harvest season, growth geography, and extraction and purification
methods, which makes commercialization difficult. The complex structure
of glycans is one of the bottlenecks in commercializing bioactivities, and
enzymatic deconstruction into more defined small units may be a way to
achieve better-defined molecules that are more suitable for the applica-
tions. Enzymatic treatment, as mentioned, can be a useful tool for the nec-
essary modification of the compound structure to achieve structures with
bioactivity in humans. However, better knowledge about the structures
and activities of both enzymes and biocompounds is crucial.
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12
Application of Nanotechnology
for the Bioengineering of Useful
Metabolites Derived from Algae and
Their Multifaceted Applications
Charles Oluwaseun Adetunji1*, Olugbemi T. Olaniyan2, Inobeme Abel3,
Ruth Ebunoluwa Bodunrinde4, Nyejirime Young Wike5,
Wadzani Dauda Palnam6, Juliana Bunmi Adetunji7, Phebean Ononsen Ozolua1,
Arshad Farid8, Shakira Ghazanfar9, Olorunsola Adeyomoye10,
Muhammad Akram11, Chibuzor Victory Chukwu12
and Mohammed Bello Yerima13
Applied Microbiology, Biotechnology and Nanotechnology Laboratory, Department
1
of Microbiology, Edo State University Uzairue, Iyamho, Edo State, Nigeria

2
3
Department of Chemistry, Edo University Iyamho, Auchi, Nigeria
4
Department of Microbiology, Federal University of Technology Akure, Ondo State, Nigeria
5
Department of Human Physiology, Faculty of Basic Medical Science, Rhema
University, Aba, Nigeria
6
Crop Science Unit, Department of Agronomy, Federal University, Gashua,
Yobe State, Nigeria
7
8
Gomal Center of Biochemistry and Biotechnology, Gomal University,
Dera Ismail Khan, Pakistan
9
National Institute for Genomics Advanced Biotechnology (NIGAB),
National Agricultural Research Centre (NARC), Islamabad, Pakistan
10
11
Department of Eastern Medicine, Government College University Faisalabad,
Punjab, Pakistan
12
Department of Microbiology, Edo State University Uzairue, Iyamho, Edo State, Nigeria
13
Department of Microbiology, Sokoto State University, Sokoto, Nigeria
285
Abstract
Globally, algae microorganisms are being used for several purposes in the food,
pharmaceutical, and medical sectors because of the beneficial drugs and bioactive
ingredients derived from them. For example, algae metabolites like lipids, pro-
teins, and polysaccharides are being used as capping agents in green nanoparticles
biosynthesis. Therefore, algae can utilize a large amount of waste materials from
the environment and convert them into useful products like biofuels, which are a
cheap, eco-friendly, and green substitute for fossil fuels. Several biomolecules like
β-carotene, zeaxanthin, lutein, phycocyanin, vitamins B12 and E, palmitoleic acid,
linolenic acid, oleic acid, cyanovirin, and astaxanthin are essential in the biological
process of biofuel production. Furthermore, over the past decades, nanotechnol-
ogy has been at the forefront of the improvement of drug delivery. This chapter
reviews the various types of nanoparticles derived from algae and the key role
they play in medical and pharmaceutical fields are evaluated. The mode of action
as anticancer activity and the different types of algae that can be produced from
nanoparticles are highlighted. Also discussed is the application of algae nanoparti-
cles in the cosmetics industry for anti-aging, antioxidant, antibacterial, antifungal,
and antiviral products.
Keywords: Nanotechnology, algae, metabolites, biomolecules, antioxidants,

antibacterial, antifungal, antiviral
12.1 Introduction
It has been estimated and documented that in 2050, the global human
population will hit almost 10 billion. This alarming prediction may likely
cause serious attendant issues that need to be addressed over the next 30
years like climate change, poisonous gas emissions, greenhouse effect,
global warming, and the energy crisis [34–36]. The best way to counter
these issues is to use eco-friendly “green” bioactive materials derived from
plants and microbes that are capable of improving the natural qualities of
the environment, and which can also serve as a perfect alternative to the
fossil fuels consumed daily [37, 38].
Globally, microorganisms are being used for several purposes in the
food, pharmaceutical, and medical sectors because of the beneficial drugs
and bioactive ingredients derived from them [1–18]. Most of the photo-
synthetic eukaryotic and prokaryotic organisms under the green algae
and cyanobacteria group, which are commonly found in ponds and lakes,
are responsible for the production of about 50% of the oxygen in Earth’s
atmosphere [19–24]. Algae have the natural ability as quenchers to fix
atmospheric CO2 and NO2 discharged from various sources [25, 26, 33].
Algae Nanotechnology and Bioengineering 287
More so, algae can utilize a large amount of phosphorus and nitrogen
from waste materials by converting them into biofuels that are cheap, eco-
friendly, and green [27–30].
A variety of bioactive metabolites derived from algae and micro-
algae have been exploited by Olson and Ingram [31], Aratboni et al. [34],
Mata et al. [32], and Sharma and Sharma [33]. Haematococcus pluvia-
lis, Dunaliella species, and Chlorella vulgaris are some good examples of
algae that can produce metabolites rich in β-carotene, zeaxanthin, lutein,
phycocyanin, vitamin B12 and E, palmitoleic acid, linolenic acid, oleic
acid, cyanovirin and astaxanthin pigments, vitamins, fatty acids, and
proteins. These metabolites can perform the functions of an antibiotic,
anti-enzymatic, antialgal, antiviral, and antifungal [39]. They can be also
utilized as food additives, feedstock for the production of biomethane, bio-
oil, biodiesel, bioethanol, cofiring, and bioelectricity through fermentation
[40]. The economic potential derived from algae as biofuels is very vast
with their attendant sustainable values to substitute organocarbon fuels.
Over the past decades, nanotechnology has been at the forefront in
the improvement of drug delivery of the chemical, biological, and phys-
ical characteristics and functionality of useful products [41]. Currently,
nanoparticles prepared from Pd, Au, Pt, and Ag (noble metals) have been
used with inorganic and microbial agents to extensively combat and con-
trol infections in clinical medicine, agriculture, and food engineering [42,
43]. However, silver nanoparticles have attained a greater amount of atten-
tion over Cu and Au nanoparticles because of their surface plasmons and
reverberation energy. More so, silver nanoparticles have several applica-
tions in antimicrobial, diagnostic, detection, optoelectronics, catalysis, and
drug delivery design. The use of silver nanoparticles in the pharmaceuti-
cal and medicine manufacturing sector is based on their low toxicity in
the cells of humans and their high-temperature stability [44]. Sargassum
wightii Greville, a marine alga, is widely used with silver nanoparticles as a
novel monodisperse bioreducer of wastes and toxins [45, 46]. This chapter
evaluates the novel application of nanotechnology for the bioengineering
of useful metabolites derived from algae strains.
12.2 Various Types of Nanoparticles Derived

from Algae
Over the past few decades, the production of biogenic metallic nanomate-
rials from plant extracts and microorganisms like actinomycetes, seaweeds,
microalgae, and algae have attracted serious attention due to their wide-
spread utilization in physiochemical and biomedical fields. Several bio-
molecules are used in reducing the metallic ions in these contaminant-free
nanomaterials for their economic benefits, eco-friendly nature, and energy
efficiency. Water-based plant metabolites, like co-enzymes, alkaloids, ter-
penoids, phenolic compounds, flavonoids, steroids, saponins, tannins, and
other nutritional compounds, are utilized as reducing agents. Studies have
revealed that algal membrane contains high levels of lipids, proteins, and
polysaccharides, which function as capping agents in green nanoparticles
biosynthesis. The methods adopted by researchers for the biosynthesis of
metallic nanoparticles are environmental, biomedical and particle char-
acterization techniques. They suggested that large-scale industrial pro-
duction of metal nanoparticles should be encouraged owing to their wide
range of applications through the utilization of natural resources like algal.
Also, the issues associated with clearance, distribution, excretion of bio-
synthesized nanoparticles in the biomedical application need a thorough
evaluation. The medical applications of these metallic nanoparticles, such
as treatment and diagnosis of different diseases, related to their bioavail-
ability and biocompatibility need serious research study.
According to Deepali et al. [47], since nature is made up of biomolecules
derived from yeast, plants, fungi, and algae, they are known to actively play
a significant role in the biosynthesis of nanoparticles. The mechanisms and
biogenic production of nanoparticles from algae were investigated by the
authors for cost-effective and eco-friendly approaches to stimulate green
production. They highlighted the medical applications, such as biosensors
and biocatalysts from diverse types of algae; though not all types of algae
can be utilized for the bioproduction of nanoparticles as some are very
toxic due to the presence of very dangerous materials.
Dipannita et al. [48] evaluated the green algae Rhizoclonium fontinale,
Chara zeylanica, Ulva intestinalis, and Pithophora oedogonia for their pos-
sible utilization in the production of nanogold. From their results, it was
confirmed that the algae R. fontinale and U. intestinalis, generated nanopar-
ticles intracellularly of different shapes but C. zeylanica and P. oedogonia
showed negative results in the biosynthesis of nanoparticles.
Khwaja et al. [49] revealed that algae of all the aquatic organisms are a
very important source of active biomolecules as a result of a large number of
proteins, alcohols, fats, pigments, carbohydrate, sugars, nucleic acids, car-
boxylic acids, and other secondary metabolites, such as macrolides, alka-
loids, peptides, aromatic compounds, terpenes, which are capable of acting
as reducing agents during the active fabrication of nanoparticles. During
the bioproduction process, the authors utilized different approaches for
characterization, including Fourier transform infrared spectroscopy, scan-

ning electron microscopy, UV-Vis spectroscopy, transmission electron
microscopy, diffraction, dynamic light scattering, energy-dispersive X-ray
spectroscopy, and X-ray.
Ramakrishna et al. [50] reported that due to the toxic effects generated
by the current nanoparticles, researchers have urgently sought alternative
ways to develop eco-friendly, cost-effective, nontoxic nanoparticles from
algae. Thus, the authors synthesized gold nanoparticles from marine brown
algae under ambient temperature and discovered that the compound has
hydroxyl groups.
Shanmugam et al. [51] revealed that for many years the production of
metallic nanoparticles from algae remained grossly understudied, and it
has been only recently that the nontoxic, eco-friendly, and fast-growing
properties of algae have found use in diverse biomedical applications.
The authors evaluated the use of Turbinaria conoides algae extract for the
production of nanogold and from their findings using Fourier transform-
infrared spectroscopy for the confirmatory test, it was discovered that the
algae contain a large number of biomolecules such as fucoidan, plus poly-
phenolic substances.
Nikita et al. [52] discovered that in recent times, the production of
nanoparticles has received tremendous attention from biomedical sci-
entists due to their vast applications. They noted that the synthesis of
nanoparticles has moved from the traditional chemical or physical to the
biological method of production from diverse microorganisms. Many ben-
eficial enzymes from metabolic activities in these algae have shown prom-
ising effects in the production, thus the authors gave an overview of the
role of many beneficial microorganisms, their shortcomings together with
the prospects of gold colloids derived from algae in biomedical sciences.
Both the intracellular cytoplasmic vesicular (magnetosomes) and extracel-
lular periplasmic space in these algae have shown the capacity to synthe-
size nanoparticles.
Leela and Anchana, [53] revealed that macroalgae are known to pos-
sess the ability to generate secondary metabolites like fucoidan and
carrageenan with diverse industrial applications such as anticancer,
anti-inflammatory, and antioxidant properties. Thus, the authors per-
formed a study to establish the bioproduction of silver nanoparticles from
macroalgae Hypnea cervicornis. Various molecular characterizations
were done, including tests on the biological activity such as their anti-
diabetic, antimicrobial, and antioxidant activity. Before now, the authors
believed not much work has been done in this regard, therefore they were
able to analyze the biological activity and confirmed the potency of these
secondary biomolecules. Khwaja and Azamal [49] reported that algae are
one of the aquatic organisms with enormous ability to synthesize bio-
molecules such as nucleic acids, macrolides, carboxylic acids, proteins,
terpenes, fats, alkaloids, alcohols, pigments, peptides, and carbohydrates,
acting as capping, stabilizing and reducing agents in the generation of
metallic nanoparticles for treating infectious diseases. Elnahas and Hala
[54] showed that the rate of spread of infections across the globe is alarm-
ing, most especially due to the increased issue of drug resistance; thus,
novel antibacterial agents are inevitable. Nanoparticles are known to be
useful for the treatment of cancer and other infectious diseases owing to
their physicochemical properties, thus the authors analyzed marine algae
as a unique microorganism for the generation of nanoparticles due to
their functional groups, such as carboxyl, hydroxyl, and amino, with the
ability to act as capping agents.
Mahdi et al. [55] demonstrated that the wide spectrum of nanopar-
ticle applications in pharmaceutical and medical sciences has attracted
huge attention in the last few decades. Microalgae have huge potential for
metal uptake and synthesis of nanoparticles during their biological activ-
ity. The authors made use of different types of algae, such as Dunaliella
salina, Nannochloropsis oculata, Chlorella vulgaris and many others, for
the bioproduction of silver nanoparticles. From their findings, it was
revealed that all the microalgae possess huge potential for the synthesis
of nanoparticles. Anju et al. [56] reported that the need to look for an
alternative source of nanoparticles from biological sources has become
imminent due to the spread of disease and infections. They extracted
silver and copper nanoparticles from green alga Botryococcus braunii
and used other molecular techniques to confirm their biological activity
against bacterial and fungal infection. Goldie et al. [57] fabricated gold
nanoparticles from Sargassum wightii and used electron microscopy to
analyze their structural integrity. It was demonstrated that the Sargassum
wightii extract was an efficient method in the fabrication of nanogold
particles.
Mohammad and Maziar, [58] recently demonstrated that silver
nanoparticles are potent antimicrobial agents even though very little is
known about the biosynthesis of silver nanoparticles from microalgae
Chlorella vulgaris and their antibacterial properties against the virulence of
Staphylococcus aureus. The authors characterized the nanoparticles using
transmission electron microscopy, energy dispersive spectrometry, scan-
ning electron microscopy, and X-ray diffraction analysis. The inhibitory
effects against S. aureus of the nanoparticles were confirmed by real-time
PCR assay due to the antagonistic effect on alpha-hemolysin expression.
In their study, Singh et al. [59] showed that the generation of nanoparti-
cles using microalgae is grossly understudied by many researchers even
though they have fast-growing, biocompatible, and nontoxic effects. In
recent years, more interest in the utilization of algae in the production of
nanoparticles is evident; thus, in their study they analyzed four micro-
algae, Chaetoceros calcitrans, Isochrysis galbana, Tetraselmis gracilis, and
Chlorella salina, for possible biosynthesis of nanoparticles and antibacte-
rial property. From their findings, it was demonstrated that the nanoparti-
cles offered great antibacterial activity against the tested pathogens. Other
studies also confirmed the potential of microalgae Gelidiella acerosa and
Kappaphycus alvarezii in the synthesis of metallic nanoparticles of tremen-
dous medicinal value. The components of algal biomass for intracellular
biosynthesis of nanoparticles could be evaluated using various techniques
by analyzing different intracellular enzymes mycelium, such as nitrogenase
enzyme, proteins, and cellular reductase enzymes, through two mecha-
nisms. The first mechanism is the attachment of metal ions on the algae
cell membrane and the second reduction to metallic nanoparticles. Vincy
et al. [108] demonstrated that organic nanoparticles can be synthesized
utilizing marine plants and microorganisms like algae. Because this area
is understudied, thus the authors showed that these organisms contain
potent biomolecules that can be utilized for biomedicine drug-resistant
pathogens in nanoscience.
Rai et al. [109] demonstrated that green algae Spirulina platensis possess
a potent ability to synthesize nanoparticles when exposed to chloroaurate
solution. They characterized the type of nanoparticles generated using
different techniques and discovered that the nanoparticles produced can
be utilized in pharmaceutical, biomedical, and technological fields due
to their eco-friendly and nontoxic nature. Shanmugam et al. [51] showed
that extract from algae can generate silver nanoparticles, thus they uti-
lized Sargassum longifolium extract exposed to AgNO3 aqueous solution
to produce nanoparticles. Characterization was done by scanning electron
microscopy and Fourier transform infrared spectrum, and discovered
that the nanoparticles possess antibacterial and high antifungal activity
against the tested pathogens. Xiangqian et al. [77] demonstrated inorganic
nanoparticles utilizing beneficial microorganisms like algae. They studied
the synthesis of metallic nanoparticles from algae for therapeutic appli-
cations such as drug delivery, gene therapy, cancer treatment, DNA anal-
ysis, biosensors, antibacterial agents, enhancing reaction rates, magnetic
resonance imaging, and separation science. Studies have revealed that in
the production of nanoparticles, different methods can be utilized such
as physical methods like pyrolysis or attrition, chemical methods, and
biological methods. The first two have many limitations due to high cost,
high energy requirement, and toxic effects. The biological methods using
algae can be described in the following way: preparation of algae extract
using a solvent like water or organic solutions, boiling, preparation of
metallic ion, and then incubation.
Tiago et al. [110] evaluated the innovative properties of novel bio-
molecules for biodegradability or biocompatibility, particularly those
from marine-based microorganisms like mammalian glycosaminogly-
cans, sulfated polymers, tissue-engineered products, and polysaccha-
rides. The authors utilized scanning electron microscope images to
evaluate the physicochemical properties. Abboud [111] showed that
aqueous extract of Chlorella vulgaris can generate silver nanoparticles
with antibacterial properties against diverse pathogens. The antimicro-
bial activity of these nanoparticles was analyzed against human patho-
gens such as Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa,
Candida albicans, and Staphylococcus aureus. From their findings, it
was discovered that the nanoparticles exhibited maximum inhibitory
property against the tested pathogens, causing cytotoxic disruption
of the cell wall, formation of pits or pores on the surface, and subse-
quently death. Kathiraven [51] utilized algal extract like C. calcitrans
for the biosynthesis of silver nanoparticles. They utilized various tech-
niques for the characterization, particularly FTIR analysis to analyze
the functional groups (phenols, amines, alcohols, aromatic rings, and
ethers) and their biological roles.
Characterization of extracellular synthesized AgNPs by cellular
reductases was done and confirmation of the functional group was
noted. Elumalai et al. [112] showed the biosynthesis of silver nanopar-
ticles using marine Cyanophyta and Oscillatoria willei, and the subse-
quent synthesized nanoparticles characterized using ultraviolet-visible
spectroscopy, scanning electron microscopy, Fourier-transform infra-
red spectroscopy, and energy dispersive spectroscopy revealed the
existence of protein-stabilizing agent, nitrate reductase. Mahdavi et al.
[113] revealed that intracellular and extracellular biosynthesis of sil-
ver nanoparticles from different marine microalgal extracts, such as
chlorophytes Tetraselmis gracilis, Chlorella salina, Chaetoceros calci-
trans, Isochrysis galbana, Nannochloropsis oculata, C. vulgaris, Chlorella
pyrenoidosa, Chlamydomonas reinhardtii, and Chlorococcum humicola,
displayed beneficial biomolecules like astaxanthins, polysaccharides,
reducing sugars, oligosaccharides, pigments, organic acids, phenol,
amino acids, flavonoids, protein and peptide, with enormous applica-
tion in biomedical sciences. Elumalai et al. [112] showed that Chlorella
vulgaris can generate gold nanoparticles through exposure to an aqueous

solution of chloroauric acid. This phytochemicals-based biosynthesis of
nanoparticles was subjected to different characterization process to ana-
lyze the functional groups and the biological activity against different
pathogens like Escherichia coli, Staphylococcus aureus, Proteus vulgaris,
Pseudomonas aeruginosa and Candida albicans. The authors revealed
that these nanoparticles are toxic to pathogens, thus offering beneficial
effects in biomedical sciences as an antibacterial agent. Jayshree et al.
[114]explored the seaweed Sargassum cinereum for possible bactericidal
activity by synthesizing nanoparticles from the algae. Different spectra
analysis was done to determine the functional groups, and the biologi-
cal activity was checked for Gram-positive and negative bacteria at Goa
Medical College and Hospital, Goa. The antimicrobial activity showed
very positive results by inhibiting the multidrug-resistant organism
(Enterobacter aerogenes).
Sangeetha and Saravanan, [115] revealed that Caulerpa racemosa
seaweed extracellularly produced silver nanoparticles in an experiment
carried out by the authors. They used different spectral analyses to char-
acterize the possible biomolecules and determine the functional groups.
Also, the biological antibacterial properties were analyzed, and the results
showed that nanoparticles produced have enhanced bactericidal activity.
Singaravelu et al. [45] showed that Ulva lactuca marine alga generated
silver nanoparticles in their study. Also, they utilized different spectra
analyses to determine the functional groups and antibacterial ability
against some pathogenic bacterial. From their investigations, they dis-
covered that the silver nanoparticles were able to inhibit the pathogens.
Sangeetha et al. [116] investigated the role of macroalgae (Ulva fasciata
and Caulerpa racemose), brown alga (Sargassum plagiophyllum, Padina
pavonica, Sargassum muticum), red alga (Gelidiella acerosa, Gracilaria
dura), and green algae (Ulva compressa, Ulva reticulate) in the produc-
tion of silver nanoparticles and their antibacterial activity. They revealed
that these macroalgae were able to synthesize a large number of nanopar-
ticles and possess huge antibacterial activity against S. aureus and Proteus
mirabilis. After incubating the algal extract solution, the marine algae
extracellularly biosynthesized silver nanoparticles, thus exhibiting the
highest antibacterial and antifungal activity against pathogens according
to their reports.
Mohandass et al. [117] reported on the use of the marine alga Sargassum
wightii to produce gold nanoparticles. This process was done by expos-
ing the alga to aqueous chloroauric acid and then utilizing several spec-
tra analyses to determine the compound and their functional groups.
Tikariha et al. [118] revealed that gold nanoparticles have a wide range
of applications across different fields and could be produced from micro-
organisms through a biological process in nanobiotechnology using algae
Sargassum natans biomass. Sivakumar et al. [119] analyzed the role of
aqueous seaweed extract of Lobophora variegata in the bioproduction
of silver nanoparticles using several spectral analyses to characterize the
biomolecules produced and their bactericidal, anticancer, antifungal,
antiviral properties against bacterial pathogens. The authors were able to
establish their biomedical properties and many other diverse applications.
Dahoumane et al. [120] demonstrated that microalgae have tremendous
application in biotechnology due to overexpression of pigments, synthe-
sis of nanomaterials, biofuel, and bioremediation applications in physiol-
ogy and nanobiotechnology. Biomolecules extracted intracellularly from
microalgae like Chlorella vulgaris have been reported to display a bene-
ficial role in biomedical sciences with diverse applications. Furthermore,
chalcogenide-based nanomaterials from microalgae provide an efficient
way of removing mercury from their environment, thus phytochelatin
biomolecule produced by these microalgae promotes the fabrication of
nanoparticles intracellularly.
Singh and Singh [121] discussed how recent expansion in the field of
nanobiotechnology has been witnessed due to growing interest in the
utilization of nanomaterial in various fields. Production of nanomateri-
als from algae has offered many opportunities in biomedical sciences
such as ultrasound medical imaging, drug delivery, biosensor, therapeu-
tics, diagnostic role owing to their nontoxicity, low cost, and faster rate
of production. The biomolecules generated from the algae are known to
have anticancer, antifungal, wound-healing, and antimicrobial properties.
The process involves the generation of algae extracts, heating, and intra-
cellular or extracellular synthesis through reducing agent. Dhavale et al.
[122] investigated the silver nanoparticles produced from microalgae
that have been reported to show excellent antibacterial properties owing
to their large surface area, biodegradability, and biocompatibility. Negm
Mohammed et al. [123] revealed that biological marine extracts of differ-
ent marine algae, U. fasciata, P. capillacea, C. mediterranea and Grateloupia
sp., are shown to possess the ability to synthesize nanoparticles. They were
tested for their antibacterial activity against some pathogens, and thus it
was revealed that the nanoparticle inhibited the growth of the bacteria.
Sahayaraj et al. [124] revealed that in recent times, different methods have
been developed to carry out nanoparticle production in microalgae. The
authors utilized marine algae Padina pavonica (Linn.) thallus broth for
extracellular biosynthesis of silver nanoparticles. Different spectra analyses
were carried out to determine the functional group and biological activity.
Biosynthesis of metallic nanoparticles displayed the highest antibacterial
activity against human pathogens. Negi et al. [60] revealed that nanoparti-
cles provide diverse opportunities for a widespread biological application
like managing environmental pollutants, degradation of organic dyes, and
therapeutic agents in biomedical sciences.
12.3 Nanoparticles from Algae and the Key Role They

Play in the Medical and Pharmaceutical Sectors
Vijay et al. [61] reported the ability of microalgae to biosynthesize silver
nanoparticles from extracellular proteinaceous pigment C-phycocyanin
and polysaccharide with huge biomedical potential for antibacterial activ-
ity against dangerous pathogenic microorganisms. Sathishkumar et al.
[62] showed that eco-friendly silver nanoparticles biosynthesized from
aqueous extract of Trichodesmium erythraeum microalgae displayed pos-
itive antioxidant and free radical scavenging, and antibacterial potential
against some drug-resistant microbial strains. Lari and Khosravitabar [63]
revealed that algae are one of the most valuable marine-based microorgan-
isms with a lot of latent biomolecules for medical and pharmaceutical appli-
cations. Recently, the authors carried out a study to synthesize zinc oxide
nanoparticles from Sargassum muticum algae and evaluate their therapeu-
tic value on cancer cells. From their observation, it was discovered that
the nanoparticles induced apoptosis on cancerous cells, thus confirming
the beneficial role of green-synthesized zinc oxide nanoparticles through
inhibition of angiogenesis. Aditya et al. [64] discovered that marine algae
possess high levels of bioactive metabolites that are of tremendous benefit
in biomedical, nutraceutical, and pharmaceutical sectors for possible drug
development against many diseases.
Jayaraman et al. [65] carried out a study to investigate the anti-
inflammatory, anticoagulant, and antidiabetic activity of gold nanoparticles
synthesized from Turbinaria conoides algae. From their study, they discov-
ered that the nanoparticles demonstrated potent anti-inflammatory, anti-
coagulant, and antidiabetic properties. David et al. [66] revealed that the
utilization of nanoparticles across the different sectors has increased expo-
nentially in the last few years. They revealed that zinc oxide nanoparticles
offer huge potential in nanophysiology for effective interactions with mem-
branes, biomarkers, or enzymes, thus exhibiting anticancer, wound-healing,
antibacterial, anti-inflammatory, and antioxidant properties for an improved
state of health. Karthick et al. [67] demonstrated that a diverse range of

antimicrobial agents is generated from marine-based algae for possible
development into drugs through nanobiotechnology. Infections caused by
pathogenic microorganisms portend serious health risks across the different
countries with increased development of drug resistance against many syn-
thetic drugs. Therefore, scientists are looking for alternatives. Today, many
wound-dressing materials are coated with antibacterial agents derived from
beneficial microbes against human pathogenic bacteria. Studies have shown
that nanoformulation coating facilitates increased air permeability and anti-
bacterial activity in wound dressing.
Patil et al. [68] showed that silver nanoparticles derived from Sargassum
wightii marine brown macroalgae were characterized by different spectral
analyses to establish the functional groups. The biological activity was inves-
tigated against some selected pathogenic microorganisms like Escherichia
coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneu-
moniae. The authors revealed that the nanoparticles showed antibacterial
activity against the tested pathogens. Samydurai et al. [69] investigated
the antibacterial activity of algal-based proteins like phycocyanin, ceph-
alosporine derivative cefotaxime nanoparticles against human pathogenic
bacterial strains. The functional groups of nanoparticles drug conjugate
were established using spectral analysis, thus the authors confirmed that
phycocyanin nanoparticles derived from algae are an effective antibacterial
agent. Adeola et al. [70] showed that nanoparticles derived from beneficial
marine algae could offer an effective diagnostic approach, drug delivery,
biosensors, nanorobots, endocytosis, transcytosis, drug trafficking, drug
targeting, immune sensors, membrane interaction, sink effect, neuropro-
tection, and nanocarriers for the specific molecule in health or disease
condition like diabetes, Parkinson’s disease, cancer, Alzheimer’s disease,
multiple sclerosis, infectious or inflammatory diseases, neovascularization,
neoplastic disorders, rheumatoid arthritis, and cardiovascular diseases.
The authors demonstrated the multifunctional role of nanomaterials like
peptidic nanoparticles, nanoporous, nano-enabled scaffold device, den-
drimers, nanogels, liposomes, nanoemulsions, polymeric nanoparticles,
nanosuspensions, and solid lipid nanoparticles in physiology, biomedical
engineering, and molecular biology.
De Jesus Raposo et al. [71] revealed that microalgae or macroalgae
possess diverse bioactive natural products for different pharmaceutical,
biomedical and medical devices, cosmetics, and food with medicinal
value. Polysaccharides and other extracellular-derived biomolecules are
known for their anticoagulant, antithrombotic, antitumor, and immuno-
modulatory ability; and as antinociceptive, cardioprotective, angiogenic,
gastroprotective, hepatoprotective, cancer preventive, hypoglycemic, anti-

biotics, antioxidants, and anti-inflammatory and antilipidemic agents
based on their physicochemical characteristics. Many of these biomolecules
are very potent for drug delivery, regenerative biomedicine, therapeutics,
wound management, bioadhesives for soft tissue closure, biolubricants,
vaccine development, biotextiles, and medical fibers. Studies have revealed
that gold nanoparticles can be utilized for the delivery of drug molecules
into different cells for gene delivery application of large biomolecules in
cancer, then subsequently upregulate cell cycle inhibitor proteins, inhibit
proliferation, and inhibit expression of NF-kappa B and induction of apop-
tosis. Wheat is one of the most consumed important strategic crops in the
agricultural sector in Egypt. Many nutraceutical products are derived from
wheat, thus improvement in the cultivation and bioprocessing is encour-
aged by the application of nanobiotechnological microalgae products to
increase yield and promote high quality. This will enhance wheat resis-
tance to biotic stress or diseases, increase wheat yield productivity, increase
the antioxidant enzymes, and improve wheat glutamine and protein qual-
ity. Thomas and Rangaswamy [72] revealed that eco-friendly metallic
nanoparticles derived from Padina pavonica can be utilized for pharma-
ceutical and biomedical purposes. The antimicrobial properties of gold
nanoparticles have been confirmed against different pathogenic bacterial
like Bacillus subtilis and Escherichia coli. The authors revealed other appli-
cations in cosmetics, foods, and consumer goods or products. Sebastian
and Mohammed [73] synthesized zinc ferrite nanoparticles from Chlorella
pyrenoidosa marine-based microalgae by sol-gel technique. They revealed
that the biomolecules derived from C. pyrenoidosa can serve as dietary
supplements for treating high blood pressure, hypercholesterolemia, and
enhance immune functions. Furthermore, marine-based algae equally
produce iron during cellular metabolism which is an essential micronu-
trient for neuronal growth and development. Mitra et al. [74] showed the
beneficial role of nanoparticles derived from beneficial algae in human
health across various systems like the respiratory, gastrointestinal, and
the immune system; and neurophysiology, reproductive biology and the
environment. The antibacterial and inflammatory properties were equally
confirmed by the authors and suggested possible incorporation into drug
formulations for diagnostic and therapeutic purposes.
Filip et al. [75] revealed that extracellular biosynthesis of silver nanopar-
ticles from Lactobacillus sp. strain possess antimicrobial and antifungal
activity in different pathogenic organisms tested with possible application
in physiology, food, or the cosmetics industry. Hua [125] described the bio-
medical application of nanocellulose derived from beneficial marine-based
Cladophora macroalgae due to their unique physicochemical characteris-

tics. In human dermal fibroblasts and osteoblastic cells, nanoparticles were
able to suppress the inflammatory response of macrophages/monocytes
and pro-inflammatory cytokine TNF-α. Ibraheem et al. [76] revealed the
antimicrobial activity of silver nanoparticles derived from Acanthophora
specifera. In their experiments, different spectral analyses were utilized to
confirm their functional group, and subsequently the antibacterial prop-
erties were confirmed against the tested pathogenic organisms such as
Salmonella sp., Escherichia coli plus yeast strain Candida albicans.
12.3.1 Anticancer Activity

Xiangqian et al. [77] demonstrated that increased interest in their devel-
opment of biomolecules derived from beneficial microorganisms has been
witnessed in the last few decades. They suggested that more research is
needed to establish and elucidate the mode of action and enhance the effi-
cacy of many of these biomolecules. The authors noted that improvement
in diagnostic and treatment protocol of several human diseases could
be enhanced through the adoption and development of nanoparticles
derived from intracellular and extracellular secretion of beneficial algae.
The authors revealed that the microbial genome could be manipulated to
control large-scale nanoparticles synthesis for biomedical applications.
Wang and Jiang [78] showed that the physiological mechanism involved in
anticancer activity synthesis of pro-inflammatory interleukins IL-2, IL-12
plus cytokine interferon-gamma (INF-γ) increases the activity of the nat-
ural killer cytotoxicity cells, upregulates the secretion of IFN-γ, induces
apoptosis by the immune-stimulated macrophages, activates Toll-like
receptor-4 (TLR-4), competent receptor-3 (CR-3), cluster of differentiation
14 (CD14); plus acts as a scavenging receptor, produces NO, and stimulates
intracellular signaling pathways involved in protein-kinases by polysac-
charides, arabinogalactans, and carrageenans.
Li et al. [79] revealed that localized hypoxia in a cancerous cell is a
great drawback to cancer treatment, thus reoxygenation would be the
best approach towards effective management of cancer cells. To achieve
this, nanocarriers would be deployed to increase the local oxygen content
towards enhancing therapeutic efficacy. Studies have revealed that a high
intake of nanocarrier could generate toxicity, thus there is a need to search
for alternatives that will be biocompatible and bioavailable. Recently, much
interest has been renewed in the utilization of microalgae like Chlorella vul-
garis in the development of nanocarrier. These microorganisms are known
to generate oxygen by photosynthesis due to a large amount of chlorophyll.
Here, the authors explored ways by which algae can be combined with
radio- or photodynamic therapy utilizing bioengineered C. vulgaris. From
their study, it was confirmed that microalgae by laser irradiation increase
tissue oxygenation, improve tumor hypoxia, generate reactive oxygen spe-
cies, and enhance cancer cell killing through algae-enhanced radio-plus
photodynamic therapy.
Hatakeyama et al. [80] discussed how cancer is one of the leading
causes of high mortality rates throughout the world. Many factors have
contributed to this such as aging, population explosion, and lifestyles.
Nanoscience has led to the discovery of several ways in which cancer can
be treated such as nanoparticles cellular imaging, enhanced diagnosis, and
drug delivery. Many marine-based microorganisms, such as Desertifilum
sp. and Anabaena sp., have been shown to synthesize biomolecules that
can be utilized for the production of nanoparticles, thereby causing cell
shrinkage, nuclear damage, chromatin condensation, chromatin margin,
cell detachment, clustering, mitochondria, and endoplasmic reticulum
interaction, inhibition of angiogenesis and cytotoxic effect. Singh et al. [59]
revealed that the biological production of nanoparticles is highly biocom-
patible using diverse beneficial microorganisms. Studies have shown that
metallic nanoparticles can be utilized for the treatment of cancer.
El-Nahas et al. [54] showed that revolutionary changes in the manage-
ment of cancer have been achieved through the development of nanopar-
ticles. The authors revealed gold nanoparticles synthesized from aqueous
extract of Corallina officinalis and Pterocladiella capillacea red alga, and
brown alga Laminaria japonica. They confirmed the antitumor activity of
the nanoparticles against human breast cancer and attributed the thera-
peutic effects to the high presence of polyphenol content like bromophe-
nols, tannins, catechin, epigallocatechin gallate, epicatechin, gallic acid
plus flavonoids in the nanoparticles and electrostatic interactions causing
cytotoxic and antimitotic activity. Mahdi et al. [55] identified red algae like
Marginisporum crassissimum, Kappaphycus alvarezii, Gracilaria termistip-
itata, Phoma herbarum, Porphyra dentate, Lophocladia sp., Lithothamnion
sp., and Laurencia sp. as the most potent sources of active biomole-
cules, like Dactylone, 2,7-naphthyridine, 3,6-anhydrous-D-galactose, and
D-galactose, against cancer cells. Sriram et al. [81] revealed that gold and
silver nanoparticles have strong anticancer activity and can be generated
from marine-based microalgae like Hypnea sp., Sargassum longifolium,
and Sphaerococcus coronopifolius. These nanoparticles are known to mod-
ulate several signaling cascades involved in inhibiting tumor progression
through active biomolecules such as alkaloids. Table 12.1 shows the dif-
ferent types of algae that can be produced from nanoparticles. Oliveira
Table 12.1 Different types of algae that can be produced from nanoparticles.
S/no. Algae species Nanomaterials References
1. Caulerpa racemosa Ag Edison et al. [126]
2. Chlorella pyrenoidosa Ag Aziz et al. [127]
3. Chlorella vulgaris Pb Eroglu et al. [128]
4. Codium capitatum Ag Kannan et al. [129]
5. Euglena gracilis Ag Li et al. [130]
6. Hypnea musciformis Ag Vadlapudi and
Amanchy [131]
7. Gelidiella sp. Ag Devi et al. [132]
8. Laurencia papillosa Au Montasser et al. [133]
9. Gracilaria corticata Ag Kumar et al. [134]
10. Padina gymnospora Au Shiny et al. [135]
11. Rhizoclonium fontinale Ag Sahayaraj et al. [136]
12. Gracilaria edulis Ag Priyadharshini et al.
[137]
13. Sargassum boveanum Pd Moimen et al. [138]
14. Nannochloropis oculata Ag El-Kassas and Ghobrial
and Tetraselmis [139]
tetrathele
15. Sargassum muticum Ag Moorthi et al. [140]
16. Padina tetrastromatica Ag Rajeshkumar et al.
[141]
17. Sargassum wightii Pd Prasad et al. [143]
18. Pithophora oedogonia Ag Sinha et al. [143]
19. Spirulina platensis Ag Suganya et al. [144]
20. Pterocladia capillacea Ag El-Kassas and Ghobrial
[139]
(Continued)
Table 12.1 Different types of algae that can be produced from nanoparticles.
(Continued)
S/no. Algae species Nanomaterials References
21. Turbinaria conoides and Au Ramakrishna et al.
Sargassum wightii [145]
22. Sargassum ilicifolium Ag Kumar et al., [146]
23. Sargassum polycystum Ag Kanimozhi et al. [147]
24. Sargassum muticum Ag Jena et al. [148]
25. Spirogyra varians Ag Pinjarkar et al. [149]
26. Tubinaria conoides Ag and Au Vijayan et al. [150]
Rajeshkumar et al.
[151]
27. Sargassum longifolium Ag Rajeshkumar et al.
[152]
28. Urospora sp. Ag Suriya et al. [153]
29. Tubinaria ornate Ag Krishnan and Nalini
[154]
30. Sargassum vulgare Ag Govindaraju et al. [155]
31. Ulva faciata Ag Rajesh et al. [156]
32. Ulva lactuca Ag Sangeetha and
Saravanan [115]
et al. [82] revealed in their study that marine-based microalgae possess a

rich source of active biomolecules against cancer, which could be explored
for drug formulation and development in the pharmaceutical sector. They
noted that cancer is one of the causes of high mortality rates seen across
the globe, thus there is an urgent need to develop a potent anticancer drug
to curb this major health challenge. The authors revealed that many active
biomolecules derived from these algae-like polysaccharides, phenolic com-
pounds, terpenoids, glycoproteins, carotenoids, sterols, alkaloids, chloro-
phylls, fatty acids, sulfolipids can modulate several pathways involved in
inhibitory activities, apoptosis pathways, key cellular processes, angiogen-
esis, invasion, migration, and cell cycle regulation processes.
12.4 Algae-Derived Nanoparticles and Their Key Role

in the Cosmetics Industry
Pigments like fucoxanthin obtained from algae, such as Laminaria japon-
ica, Macrocystis, and Alaria chorda, assist in reducing the action of tyrosi-
nase and melangensis [83]. Melanogenesis is known as a process caused by
exposure to direct sunlight over a long period of time, thereby leading to
the tanning of the skin color during this period of exposure. Sunlight radi-
ation aids the synthesis of an enzyme that catalyzes dihydroxyphenylala-
nine is the cause of melanin synthesis, which helps in the speed-up of the
reaction in the production of melanosomes that later develop into melanin
and a further process leading to skin deteriorating [78].
12.4.1 Algae-Derived Nanoparticles as Moisturizer

Moistening creams are usually composed of a mixture of chemical com-
plexes that help to soften the skin. When the skin is not moisturized well
it could lead to eczema, so it helps to prevent wrinkling and dryness of
the skin. Researchers have revealed that polysaccharides from algal like
Codium tomentosum and S. japonica help in water absorption, bringing
about a soothing effect that aids in proper circulation of water, keeping the
skin moist in extreme weather and environmental conditions [78].
12.4.2 Algae-Derived Nanoparticles as Skin Sensitizing

and Thickening Agents
Lotions and creams with increased water contents are usually stabilized
through the addition of gelatinous substances such as vegetable gum.
Gracillaria and Gellidium have a binder in their cell wall making them use-
ful in stabilizing highly watery creams and cosmetic products to regulate
consistency. Some algal is also used as skin sensitizers due to the presence
of phycocyanin color, some proteins, vitamins, and carrageenans, which
were found to be important for the skin. Algal has been used widely as an
organic component in the production of cosmetics and helps to add more
value to the products [84]. When people begin to age, the skin starts to
become fragile and soon loses the ability to retain hydration [78]. Before
the advent of improved technology, macroalgae have long been used as
phycocolloids in making gels. They are composed of natural moisturizers
and help the skin produce collagen [85].
12.4.3 Algae-Derived Nanoparticles as Anti-Aging Agents

Aging of the skin is known to happen when there is a lack of skin elasticity,
the appearance of the lines, sagging of the skin, breakdown of the skin,
dryness of the skin, and also skin color change as one gets older [86]. The
human skin is usually faced with a lot of harsh weather, stress, and environ-
mental conditions, bringing about the above reasons for skin aging. Skin
wrinkling is usually caused due to overexposure to heavy metals (Ag, Pb),
lack of moisture in the epidermis, and poor nutrition. Reactive oxygen spe-
cies, like singlet oxygen, are known to be the most prevalent cause of skin
aging. Innovative scientific studies have utilized fat-soluble antioxidants
and carotene for rejuvenation, thereby protecting the skin against aging
and also alleviating cancer among users of chemically infused commercial
products [87]. Beta-carotene found in green and red algae help reduce pre-
mature skin aging [157]. Porphyra umbilical is an alga that produces amino
acid which protects the skin from UV radiation that is liable to cause dam-
age to the skin. Kelman et al. [88] reported the use of the following algae as
anti-aging agents: Turbinaria ornata, Polysiphonia, Ahnfeltiopsis, Padina,
Colpomenia, Laurencia, Gracilia, and Hydroclathrus.
12.4.4 Algae-Derived Nanoparticles as Antioxidant Agent

Antioxidants are known to help in tightening the skin, limit inflammation
of the skin, and reduce skin wrinkles. The presence of vitamin A makes this
possible, increasing the elasticity of the skin. Cyanobacteria produce a large
amount of vitamin A (retinoic acid) [89]. Spirulina maxima and Chlorella
vulgaris contain vitamins that help to tone the skin and treat dandruff.
Another algal used as cosmetics is Irish moss (Sagina subulata), which is
used as an anti-inflammatory, as a skin moisturizer, and for soothing the
skin. Dunaliella salina, Spirulina, Chlorella vulgaris, Ulva lactuca, Postelsia
palmaeformis, Porphyra umbilicalis, and Ascophyllum nodosum are used in
the synthesis of collagen, in softening the skin, as a conditioning agent to
the skin, and anti-aging/anti-wrinkling agent [85].
12.5 Algae-Derived Nanoparticles as Antibacterial

Agent
Salari et al. [90] assayed the antibacterial activity of AgNPs synthesized
using macroalgae Spirogyra varians for their antibacterial activity against
Bacillus cereus, Klebsiella, and Pseudomonas aeruginosa in comparison to

the conventional antibiotics. The mechanism behind the inhibition of the
bacterial species could be due to the AgNPs penetration into the microbial
cell, leading to the production of hydrogen peroxide and death of the cells.
This could be caused by the rate at which the NPs were able to penetrate
the cell membrane of the bacteria [91]. There was a higher inhibitory effect
on Gram-positive bacteria (Enteromorpha flexuosa) than that of Gram-
negative bacteria [92]. Spirulina platensis aqueous extract showed a higher
zone of inhibition against P. aeruginosa. The authors concluded that both
Gram-positive and Gram-negative bacteria were susceptible to the treat-
ment and that there were different concentrations for different inhibition
zones; none of the test isolates were resistant to the nanoparticle’s treat-
ment [61]. Muthusamy et al. [93] stated that increased concentration of
silver NPs brought about an increased level of bacterial susceptibility to the
agents. There was a higher antibacterial impact in the application of AgNPs
of green synthesis against O. simlicissima [94].
Studies have been conducted on the utilization of algal NPs against the
following bacteria:
(i) Silver nanoparticles from Amphiroa fragilissima were tested

and found effective against K. pneumonia, S. aureus, and
P. aeruginosa [95].
(ii) Silver nanoparticles obtained from Acanthophora specifera
were assayed against E. coli, Bacillus subtilis, Salmonella,
and also on bacteria that have the affinity to produce bio-
film, such as S. typhii and S. flexneri [76].
(iii) Caulerpa racemosa nanoparticles were effective against S.
aureus and P. mirabilis [51].
(iv) Chlorococcum humicola exhibited an inhibitory effect on
E. coli and nanoparticles from Oscillatoria limnetica were
effective against Bacillus cereus and E. coli [94].
(v) Nanoparticles from Enteromorpha flexuosa had inhib-
itory effects on Enterococcus faecalis, Staphylococcus epi-
dermidis, S. aureus and Jania rubens nanoparticles with
inhibitory efficacy on S. aureus and E. coli [96].
(vi) Gracilaria birdiae nanoparticles were effective against E.
coli and Gracilaria dura NPs were effective against Bacillus
pumilus [97].
Silver nanoparticles from Caulerpa racemosa were examined for their

antimicrobial potential on some human pathogenic microorganisms like
S. aureus. From their findings, Shanmugam et al. discovered that NPs from
this algal species do not just disrupt the cell wall functioning but also pene-
trate the cell and stop the process of cell division leading to the death of the
cell [51]. Synthesized AgNPs from aqueous extract of Pithophora oedogo-
nia showed the highest zone of inhibition against Pseudomonas aeruginosa
followed by E. coli. The antibacterial potential of gold nanoparticles was
assayed against Gram-positive and Gram-negative bacteria. It was found
that the thin peptidoglycan layer in Gram-negative bacteria allowed easier
permeability of AgNPs and cell disruption [98].
Microalgae that are marine based are known to be physically import-
ant and possess biologically effective metabolites. These metabolites were
found to be very effective at different phases of life application. The active
ingredients of extracts from several algae demonstrated a series of anti-
microbial properties against bacteria. Studies revealed that the synthesis
of NPs from algal has been utilized and underutilized. Some researchers
reported the utilization of microalgae in the production of metallic NPs,
such as Sargassum wightii and Gelidiella acerosa; nanoparticles were also
synthesized from Spirulina platensis [45]. Merin et al. [98] reported the
effectiveness of the antibacterial activities of marine microalgae NPs on
Klebsiella sp, P. aeruginosa, and E. coli. Studies revealed that biologically
effective compounds were obtained from both macro- and microalgae.
Some strains of cyanobacteria produced metabolites extracellularly and
intracellularly, ranging in biological efficacy such as antibacterial, antiviral,
and antifungal activities. The responsive activities of the algae NPs could be
due to several factors like temperature of incubation, change in pH, dura-
tion of incubation, substrate, and the intensity of illumination [99]. The
degree of effectiveness of any bionanoparticle is usually dependent on the
method used for the synthesis of such nanoparticles [100]. Studies showed
that NPs synthesized from Microcoleus sp. were used on pathogenic bac-
teria and when the results were compared to that of the conventional anti-
biotics there was a significant difference, with the AgNPs being recorded
as more effective. The work of Volk [39] also revealed the effectiveness of
Microcoleus against P. vulgaris, Corynedacteriumm sp., B. subtilis, and E.
coli with high zones of inhibition. There was also a study on the synthesis
of different extracts from Microcoleus which were used as an antibacterial
agent against several pathogenic bacteria. The authors concluded that the
production of NPs from algae has proven to be more active and effective
in comparison with conventional antibiotics [100]. AgNPs were found to
have high antimicrobial activity on type strains of E. coli and S. aureus.
These strains were found to be susceptible to AgNPs with obvious zones
of inhibition when NPs were introduced compared to when plant extract
was administered. The zones of inhibitions obtained were also due to the
concentration of the administered NPs [68].
12.6 Algae-Derived Nanoparticles as Antifungal

Agent
Silver nanoparticles have long been used in tackling some potential patho-
genic fungal infections. The green synthesis of silver nanoparticles showed
awesome antifungal activities against A. fumigatus, Fusarium sp., and C. albi-
cans, which could be used as an antifungal agent on several diseases [101].
AgNPs were found to have a great inhibitory effect against Fusarium com-
pared to A. fumigatus, with a low zone of inhibition. Researchers revealed
that the mechanism behind the effectiveness of AgNPs could be due to the
tiny size of the NPs and the wide surface area thereby inhibiting the growth
of fungi. The shape and the reduced volume of the silver ions have elevated
the area of contact to inhibit microbial growth. There could be an attach-
ment of AgNPs that are positively charged to the microbial cell membrane,
which has a negative charge [102]. After the AgNPs enter, perforate the cell
wall, and disrupt the permeability of the cell, there is protein leakage and the
cell becomes dead. The work of Kim et al. [103] also revealed that AgNPs
could inhibit conidial growth on fungi and also exhibit the potential to hin-
der the production of spores by the fungi. The antifungal activity of AgNPs
was conducted against C. albicans, C. parapsilosis, and A. niger along with
conventional antifungal agent nystatin as a control. The AgNPs had remark-
able antifungal activity against tested strains at different concentrations. The
work was linked to the findings of Kim et al. [103], who stated that AgNPs
were more effective against C. albicans compared to the synthetic antifungal
drugs. Bringing a final cure to fungal infection could harm the host, such as
kidney and liver malfunction from overuse of amphotericin B and nystatin.
Silver ions that form compounds based on the presence of DNA have the
ability to disrupt and to stop the activity of fungal DNA, leading to cell death.
AgNPs were synthesized from plants using ribose as the reducing agent and
a stabilizer, which showed high inhibitory activity against Candida albicans
and Candida tropicalis [104].
12.7 Algae-Derived Nanoparticles as Antiviral Agent

Studies on the green synthesis of SNPs from L. coccineus hexane showed
antiviral activity against the viruses that were tested; while the extracts of
M. lutea nanoparticles hexane extract showed antiviral property only on

CoxB4 and HAV-10. There was notable inhibition of the infection caused
by viruses when the green-synthesized nanoparticles were incubated with
viruses before infection. Fatima et al. stated that the mechanism by which
this inhibition is done could be a resultant effect of the binding ability of
the SNPs to the envelope of the viral glycoproteins, thereby disrupting easy
accessibility of the host [105]. The nanoparticles could penetrate the cell
of the viruses and abort their virulent factor via interaction with the DNA
and RNA of the viruses [106]. The NPs could also disrupt the pathways
that bring about replication in the viruses [107]. Kwon et al. concluded
that the results obtained during their research are a great innovation on
the antiviral application of green synthesized nanoparticles as an effective
therapy to combat mutant and resistant virus strains.
12.8 Conclusion
This chapter discussed the application of nanotechnology for the bio-
engineering of useful metabolites derived from algae. The issues associated
with clearance, distribution, excretion of biosynthesized nanoparticles
in biomedical application, treatment, and diagnosis of different diseases,
along with their bioavailability and biocompatibility, were investigated.
Green algae like Rhizoclonium fontinale, Chara zeylanica, Ulva intestinalis,
and Pithophora oedogoniana were some of the species utilized in the pro-
duction of bionanoparticles. Findings from the review showed that many
beneficial enzymes from metabolic activities in these algae, such as poly-
saccharides, phenolic compounds, terpenoids, glycoproteins, carotenoids,
sterols, alkaloids, chlorophylls, fatty acids, and sulfolipids, have shown
promising beneficial effects in both intracellular cytoplasmic vesicular
(magnetosomes) and extracellular periplasmic space with nanoparticles.
These have also been useful for their therapeutics on cancer and other
infectious.
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13
Discovery of Novel Compounds
of Pharmaceutical Significance
Derived from Algae
Charles Oluwaseun Adetunji1*, Muhammad Akram2, Fahad Said Khan2,
Olugbemi T. Olaniyan3, Babatunde Oluwafemi Adetuyi4, Inobeme Abel5,
Ruth Ebunoluwa Bodunrinde6, Juliana Bunmi Adetunji12,
Phebean Ononsen Ozolua1, Nyejirime Young Wike7, Wadzani Dauda Palnam8,
Arshad Farid9, Shakira Ghazanfar10, Olorunsola Adeyomoye11,
Chibuzor Victory Chukwu11 and Mohammed Bello Yerima13
Applied Microbiology, Biotechnology and Nanotechnology Laboratory,

1
2
Department of Eastern Medicine, Government College University Faisalabad,
Punjab, Pakistan
3
4
Department of Natural Sciences, Faculty of Pure and Applied Sciences,
Precious Cornerstone University, Ibadan, Nigeria
5
Department of Chemistry, Edo University Iyamho, Auchi, Nigeria
6
Department of Microbiology, Federal University of Technology Akure,
Ondo State, Nigeria
7
Department of Human Physiology, Faculty of Basic Medical Science,
Rhema University, Aba, Nigeria
8
Department of Agronomy, Federal University, Gashua, Nigeria
9
Gomal Center of Biochemistry and Biotechnology, Gomal University,
Dera Ismail Khan, Pakistan
10
National Institute for Genomics Advanced Biotechnology (NIGAB),
National Agricultural Research Centre, (NARC), Islamabad, Pakistan
11
12
13
321
Abstract
The pharmaceutical and wellness markets are quickly expanding worldwide, and it
is this area that is especially alluring to shoppers. A developing piece of promising
pharmaceutical exploration today is likely connected to the creation of new phar-
maceuticals from the marine ecosystem, which continues to be a source of bioactive
compounds with great potential in new products. Adversely, since the undiscovered
capability of green growth in the pharmaceutical sector presently isn’t always being
investigated properly, there has been distrust in the immense worldwide advertis-
ing campaigns related to green pharmaceuticals. Still, the green growth industry
is developing to become one of the most encouraging wellsprings of sustainable
plant production systems that can have medical advantages as sources of proteins,
omega-3 and cell reinforcements among others. The pharmaceutical capabilities of
different green growth species are presently being considered. Various investigations
are attempting to improve a few types of green growth items that have healthful,
nourishing or pharmaceutical noteworthiness. Therefore, this chapter intends to
provide detailed information on current advances in the discovery of novel com-
pounds of pharmaceutical significance derived from algae.
Keywords: Compounds, pharmaceutical, algae, green growth
13.1 Introduction
Green growth is a wellspring of numerous likely new medications and bio-
active atoms. Living life forms have been a significant wellspring of new
naturally dynamic particles in pharmaceutical, wellness and agrochemical
ventures for quite some time. For instance, of the roughly 14,000 known
characteristic anti-infection agents, around 5,500 are made with actinomy-
cetes and around 3,300 from higher plants, of which around 90 are presently
utilized in medication. A far-reaching concentrate on green growth (at first
for the most part green growth) for naturally dynamic particles with anti-
microbials or other potential pharmaceutical purposes started during the
1990s and has gotten a lot of new consideration in the previous decade.
This has prompted the disclosure of an enormous number of new mixes
with various distinctive pharmacological and natural exercises. A portion of
these mixes are presently being analyzed in more detail for use in medica-
tion. Given the incredible assorted variety of green growth, it isn’t astound-
ing that they likewise have such a decent variety of high compounds. In East
Asia, ocean growth has been utilized as a rich wellspring of minerals, nutri-
ents and dietary fiber. They have as of late been featured as multifunctional
nourishments to help our wellbeing [55, 64, 67, 75, 76, 80, 85].
Green growth, as a rule, are discovered everywhere throughout the
world and in each biological specialty possible. Along these lines, they have
Novel Compounds Derived from Algae 323
special properties to enable them to endure even in the unfavorable con-

ditions they experience in the biological system. These extraordinary traits
are brought about by changes in their large scale and miniaturized scale
subatomic constituents in cell structures in upsetting circumstances. These
one-of-a-kind metabolites frequently have unique properties and can be
considered as bioactive mixes notwithstanding the macromolecules ordi-
narily found in green growth.
There are a great many types of green growth and just 25–30% have been
distinguished and gathered. Thusly, there is a tremendous unexplored asset
accessible for use in the pharmaceutical business. Microalgae are known to
deliver different restoratively compelling biocompounds which can be got-
ten from biomass or discharged extracellularly in the medium [90]. These
microorganisms contain numerous bioactive mixes, for example, proteins,
polysaccharides, lipids, nutrients, chemicals, sterols and different mixes of
high estimation of pharmaceutical and dietary significance that can be uti-
lized for business purposes [2–19].
Strangely, green growth assume a key job in the sea, as other marine
life forms can depend on green growth to get vital needs along the whole
natural pecking order. It is hence coherent to accept that green growth,
contrasted with other marine creatures, might be a significant wellspring
of numerous optional metabolites, including practical supplements and
related bioactive peptides. Without a doubt, green growth can be a charac-
teristic source with solid natural movement and this is drawing in light of a
legitimate concern for some researchers. Moreover, there has been a ton of
fascination in following new bioactive peptides as far as wellbeing impacts
[51]. In synopsis, a significant part of the examination has concentrated on
ocean growth to discover new utilitarian fixes. A few types of green growth
have initiated organic movement related with proteins, protein hydroly-
sates or peptides that can impact their healthy benefit as cancer preven-
tion agents [45, 50], antihypertensive medications [33], regulating resistant
[62], anticancer [78], and anticoagulants [22, 39–44]. These natural exer-
cises would be an extra favorable position to access their multifunctional
applications, including utilitarian nourishments or food sources [29, 37,
60], pharmaceutical items [31] and beautifying agents [74, 81].
13.2 Bioactive Compounds

The bioactive mixes of microalgae can be acquired straightforwardly
from essential digestion systems, for example, proteins, unsaturated fats,
nutrients and shades, or they can be integrated by auxiliary digestion.
These mixes can have antifungal, antiviral, antialgal, antienzymatic or

anti-microbial activities [27]. A large number of these mixes (cyanovirin,
oleic corrosive, linolenic corrosive, palmitoleic corrosive, nutrient E, B12,
β-carotene, PC, lutein and zeaxanthin) have antimicrobial, cell reinforce-
ment and mitigating properties, with the possibility to diminish and infec-
tion avoidance [70]. In most microalgae, bioactive mixes gather in biomass;
notwithstanding, now and again, these metabolites are discharged in the
medium; these are the exometabolites.
13.3 Pharmacological Significance of Algae

13.3.1 Antioxidative Activity
Cell reinforcements assume a significant role in the human body by dimin-
ishing oxidative responses. Specifically, superoxide dismutase, catalase,
glutathione peroxidase and non-enzymatic cell reinforcements, for exam-
ple, vitamin C, a-tocopherol and selenium, shield inner organs and tis-
sues from oxidative effect brought about by different poisonous responsive
oxygen species and receptive oxygen species [20]. Actually, between ocean
fauna and verdure, kelp is viewed as a rich wellspring of normal cancer
prevention agents [66]. This finding unequivocally proposes that there
might be extraordinary ecological changes in the sea at low light forces
and high oxygen fixations. As of late, some related investigations have
concentrated on cancer prevention agent protein hydrolysates or peptides
as opposed to extraction of ocean growth natural solvents. Furthermore,
some amino corrosive groupings with covalent bonds and related warm
solidness have increased powerful cancer prevention agent properties [77].
The cancer prevention agent action of ocean large scale and microalgae
has been explored in a few in vitro investigations, for example, DPPH
(1,1-diphenyl-2-trichylhydrazyl), hydroxyl radical, hydrogen peroxide
and superoxide anion filters dictated by electron turn reverberation (ESR)
spectrophotometric technique [66]. The red alga Palmaria palmata in
the UAE was generally presented to DPPH and peroxyl radicals when
rewarded with proteases rather than starches. What’s more, low subatomic
weight peptides or amino acids can be discharged by proteases by enzy-
matic hydrolysis, which can help increment ROS exercises [89].
In another investigation, Undaria pinnatifida EAEs arranged utilizing
proteases indicated solid DPPH and hydroxyl radical rummaging action
[40]. Moreover, marine macroalgae, Ulva fasciata, indicated a detoxifying
impact on oxidative pressure brought about by receptive oxygen species
brought about by UVB radiation. This examination recommended the

incorporation of an ascorbate-glutathione cycle with inborn mimicking
proteins into the cancer prevention agent barrier framework [79].
13.3.2 Antihypertensive Activity

Cardiovascular disease (CVD) continues to be a high risk to numerous
lives in the total population, regularly testing medical issues [46]. CVD
is known as a significant risk factor for mortality and is related to hyper-
tension. Also, the absolute number of adults with hypertension surpassing
25% in 2000 was 927 million in both wealthy and developing nations.
Furthermore, it is predicted that by 2025, an increase in CVD of roughly
60% will affect 1,566 million adults with hypertension [46]. What’s more,
hypertension causes atherosclerosis, stroke, myocardial localized necrosis
(MI), and other cardiovascular sicknesses, for example, late-stage renal ail-
ment [46]. As of late, research on new ACE inhibitors from marine growth
as an option to manufactured green growth has gotten incredible consid-
eration [51].
Subsequently, the ACE-I inhibitory force is stressed in numerous inves-
tigations dependent on protein hydrolysates [83]. Then again, the marine
growth (U. pinnatifida) peptide processing demonstrated ACE-I inhibitory
movement (213, 64.2, 90.5 and 21 μMIC50 values) against the amino cor-
rosive successions Ala-Ile-Tyr-Lys and Tyr-Lys-Tyr., -Tyr, Lys-Phe-Tyr-Gly
and Tyr-Asn-Lys-Leu. What’s more, seven other ACE-I inhibitory peptides
were disconnected from marine growth utilizing the protease S-Amano
catalyst. As indicated in a report, the IC50 estimations of isolated dipep-
tides, for example, Val-Tyr, Ile-Tyr, Ala-Trp, Phe-Tyr, Val-Trp, Ile-Trp,
Leu-Trp are 35.2, 6.1, 18.8, separately, 42.3, 3.3, 1.5 and 23.6 μM. Among
these peptides, Val-Tyr, Ile-Tyr, Phe-Tyr, and Ile-Trp show that when given
a single administration (1 mg/kg rat), the blood pressure of the sponta-
neously hypertensive rats (SHRs) decreased. In another examination,
using hot water extract of U. pinnatifida, Tyr-His, Lys-Trp, Lys-Tyr, Lys-
Phe, Phe-Tyr, Val-Trp, Val-Phe, Ile-Tyr, Ile-Trp and Val-Tyr, there was also
a significant decrease in the blood pressure of SHRs [84].
Alcalase was chosen as the most effective hydrolysate after seven com-
mercial proteolytic catalysts were used to hydrolyze Porphyra yezoensis, an
edible variety of red-green growth. Together, structure-movement linkages
proved that different peptide inhibitors had a significant impact on ACE
to substrates with C-terminal tripeptide successions. However, the amino
acids close to the C-terminal proline accumulation of particular peptides
also had an impact on the force of ACE translocation [57]. In fact, these
hydrophobic amino acids should alter even with solid movement. Along
these lines, this might be a viable component for assessing the antihyper-
tensive and ACE-I inhibitory effects. However, a significant part of the
peptides obtained from food-determined proteins’ counter ACE-I action
was estimated in vitro [57].
13.3.3 Anticoagulant Activity

One of the most complex processes in homeostasis is blood coagula-
tion. The process through which blood transforms from a liquid to a gel
and forms a blood clot is known as coagulation, often known as clotting.
Hemostasis, the halting of blood loss from a damaged vessel, may ensue,
followed by repair. Platelet activation, adhesion, and aggregation as well
as fibrin deposition and maturation are all components of the coagulation
mechanism. In order to stop draining and repair damaged divider regions
in the veins, coagulation factors are involved. In any case, by preventing
blood thickening, the coagulating process is prevented by endogenous and
external factors [42]. Thus, there is growing interest in common antico-
agulants that are secure enough for potential therapeutic uses. However,
the anticoagulant effect of kelp bioactive peptides has not been taken into
consideration. The solid anticoagulant movement of other important com-
pounds, such as proteoglycans, has been observed in marine macroalgae
and microalgae species, however [22].
Aqueous concentrations of 22 green and earth-toned green growth spe-
cies were tested as potential anticoagulants in the Jeju shoreline area of
South Korea [22].
13.3.4 Antiproliferation Activities

Malignant growth is the second leading cause of death in high income
countries and the leading cause of death overall [32]. Several diseases
are currently putting the world’s population in peril. According to 2008
GLOBOCAN research, 7.6 million disease cases have been assessed
out of an estimated 12.7 million cases that were recorded in 2008 [41].
Chemotherapy is a vitally important and promising method for preventing
and treating malignant development, and it aims to reduce disease severity
and death by postponing the carcinogenesis process [78].
Nevertheless, blockage improvement frequently occurs despite chemo-
therapy side effects. As a result, frequent sources of beneficial bioactive
metabolites were activated. In this way, ocean growth fosters a bene-
ficial source of practical ingredients and is used in cancer treatment.
Recent research suggests that peptides derived from C. vulgaris may lower
UVB levels in skin fibroblast cells [30].
Sulaimn, Shamaan, Ngah, and Yusof [86] established the influence
of the cell reinforcement catalyst status in high temperature water sepa-
rates of C. vulgaris in rodents caused by liver malignant growth in several
studies. The level of superoxide dismutase (SOD) is also decreased by all
dosages (50, 150, and 300 mg/kg body weight) for all weeks (0, 4, 8, and
12) when experimenting with various liver malignant growth-activated
groups (choline inadequacy diet). 0.1 etionin per one hundred milliliters
of water; (CDE) and control group. As a result, a protective role has been
resolved in mice with liver cancer caused by substituting or compensating
for endogenous cell reinforcement chemicals. The growth and multipli-
cation of human constant myeloid leukemia cell lines (K562) have been
tested using C-Phycocyanin, the main biliprotein isolated from high vir-
tuosity S. platensis (> 95%) [82]. As a result, K562 cells exposed to 50 M
C-phycocyanin for up to 48 hours had 49% fewer multiplications over-
all. Additionally, cytometric stream analysis of cells treated with 25 and
50 Mof C-phycocyanin for 48 hours revealed, independently, 14.11% and
20.93% of cells in the G0/G1 stage. The truth is that the transfer of cyto-
chrome c from the mitochondria to the cytoplasm confirmed the forma-
tion of apoptotic bodies as a result of the involvement of C-phycocyanin
in K562 cells [82]. When C-phycocyanin from S. platensis was rewarded
in human hepatocarcinoma (HepG2) cell lines, several studies revealed
that there was a reduced articulation of medicine 1 obstruction proteins
(MDR-1). Additionally, ROS and COX-2-intervened pathways were found
to be related to NF-B and AP-1 [69].
13.3.5 Immune-Stimulant Activity

The various useful large scale and microalgal segments are mostly respon-
sible for the medical benefits. As a result, proteins and peptides are becom-
ing popular as supplements and as possible tools for improving health.
Bioactive auxiliary metabolites can cause and animate human wellbeing
aspects, according to later in vitro and in vivo studies. Ex vivo testing using
enzymatic hydrolysis can be used to identify additional bioactive proteins
as peptides obtained from green growth proteins. Furthermore, the major-
ity of peptides are likely released and processed during gastrointestinal
digestion because they are encoded in the main algal proteins [51]. Healthy
growth Pancreatic protein hydrolyzes C. vulgaris at a rate of 20 AU/g
compound/substrate with a pH of 7.5 and a temperature of 45 °C for a
period of 4 hours [62]. Exams showed that after using depleted Balb/c mice,
he experienced both an innate and explicit immune response. Additionally,

oral administration of a protein hydrolyzate (500 mg/kg) was provisionally
finished between 8 and 3 days at a fixed time, and there was a discernible
increase in the lymphocyte pool of 128% in comparison to the benchmark
group of mice (pb0.01). In order to assess hematopoiesis, the amount of
leukocytes in peripheral blood and the bone marrow’s cellularity were
restored. The practical mobility of macrophages was also substantially
increased. In fact, the T-incited counteracting agent reactions and recov-
ery of postponed type extreme touchiness responses (DTH) were among
the revitalized humoral and cell invulnerable capacities as well [62]. On
murine splenocytes, the protease catalyst concentrate of E. cava stimulated
the immune system in vitro. As it was discovered, E. cava hydrolyzate sig-
nificantly increased the proliferative effect of splenocytes, including lym-
phocytes, monocytes, and granulocytes, when administered to ICR mice.
Additionally, compared to untreated controls, more CD4 + T cells, CD8 +
T cells, and CD45R/B220 + B cells were present overall. Additionally, there
was a reduction in the production of Th-1-type cytokines, such as TNF-an
and IFN-y, as well as mRNA articulation. As a result, cytokines of the Th-2
sort, such as IL-4 and IL-10, were improved [20].
13.3.6 Cholesterol-Lowering Activity

It has been proven that consuming phytosterols and their esters has a
cholesterol-lowering effect, resulting in a 10% to 15% decrease in serum
levels of LDL-X, one of the primary risk factors for IHD in persons with
hypercholesterolemia [61]. Patients who received antihypercholesterol-
emic drugs such statins [65] and fibrates [68] experienced a significantly
more drastic decline. Phytosterols obtained from microalgae were also
observed to have a cholesterol-lowering effect; this was accomplished
by reducing the assimilation of cholesterol from meals and reducing
endogenous cholesterol produced by the gastrointestinal system. The
statement of the intestinal quality ACAT2, which is responsible for cho-
lesterol intake in the gut [24], is restrained by schizosterol removal [58].
The ability of this concentrate to lower cholesterol is also linked to hepatic
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, a substance

involved in the synthesis of cholesterol.
The LDL-C receptor is stimulated by Schizochytrium sterols, which
promotes the removal of plasma cholesterol from the circulatory system.
According to studies, hamsters fed 0.06 and 0.3 g of schizophirrium sterol
extract per kilogram of food had their cholesterol levels drop by 19.5%
and 34%, respectively. The schizochitria sterol extricate’s bioactivity was
just as impressive as that of the positive benchmark group given yararl-sit-

osterol, a phytosterol that is already added to foods like margarine and
vegetable oils as beneficial additives. The mechanism of action of differ-
ent phytosterols differs. Extricate of blue-green growth lipid, cooperative
kind of Nostoc. Sphaeroids Kützing (N. collective) suppress the synthesis
of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and the expres-
sion of LDL receptor in human hepatoma cell lines. However, in a previous
research, this species was accounted for to be described by the proximity
of campesterol, p-sitosterol, and clionasterol [72]. The lipid of intrigue was
not recognized in this examination. By reducing mRNA articulation in the
gastrointestinal system and competing with cholesterol for the NPC1L1
carrier, B-action sitosterol’s to lower cholesterol is achieved.
13.3.7 Anti-Inflammatory Activity

By preventing the production of particularly provocative cytokines
(TNF-an) and COX-2 articulation, ergosterol isolated from edible mush-
rooms can quell the ferocious responses of LW-incited RAW264.7 mac-
rophages in vitro [54]. Chlorella ulgaris [91] and Dunalliella tertiolecta
have been reported to contain ergosterol, which exhibits similar systems of
activity by reducing the reaction caused by LPS [28]. In addition to ergos-
terol, mice by 0-tetradecanoylphorbol-13-acetic acid derivation (TPA:
solid tumor advertiser) prompted by ergosterol, 7-dehydroporiferetherol
peroxide, and 7-oxo-cholesterol (TPA: solid tumor advertiser) showed a
strong calming action with 2-0.7 mg/ear as a half inhibitory portion [91].
The microalga Dunaliella tertiolecta is thought to be a potential source
of phytosterol for the future because it has recently been linked to ergos-
terol, 7-dehydroporiferasterol, and ergosterol peroxide [34]. A synergistic
system of some microalgae phytosterols has been reported in some stud-
ies to increase the natural mobility of another phytosterol For instance,
sheep fringe blood mononuclear cells (PBMC) were stimulated to pro-
duce a combination of ergosterol and 7-dehydroporiferasterol (both from
Dunalliella tertiolecta), which was more effective than ergosterol alone in
the same focus [28]. Synergistic effects should always be taken into account
when streamlining effectiveness because microalgal phytosterols and other
metabolites are promising potential calming agents.
13.3.8 Anticancer Activity

Several studies have suggested that phytosterols may act naturally to
inhibit tumor growth [23]. For instance, human colorectal cancer cells
were cytostatically affected by ergosterol [54]. Ergosterol peroxide inhib-

ited the growth of Walker 256 carcinosarcoma cells and MCF-7 human
bosom adenocarcinoma cells in vitro [48]. 2 mol of ergosterol perox-
ide from Chlorella vulgaris effectively prevented tumor movement (77%
decrease) in mice when TPA and 7,12-dimethylbenz (an) anthracene were
present (DMBA: immunosuppressor and tumor initiator). According to
one theory, the biosynthetic polyamine chemical ornithine decarboxylase
(ODC), which is produced by TPA, is inhibited by these bioactive sterols.
Hepatocarcinoma (HepG2) cells were severely damaged by a stigmasterol
isolated from the navicula incerta, and this stigmasterol is effective at trig-
gering apoptosis by increasing the proapoptotic Bax and p53 quality’s guid-
ing principle and inhibiting the activity of the antiapoptotic Bcl-2 quality
[52]. Separated from the earthy-hued Sargassum carpophyllum growth,
fucosterols and oxygenated fucosterol shown cytotoxicity against various
disease cell lines [87].
13.3.9 Cancer Prevention Agent

The ability of phytosterols from microalgae to prevent cancer has received
scant scientific support. In any event, phytosterols from various sources
have been taken into account to provide a beneficial result. For instance,
stigmasterol from Butea monosperma strip revealed the highest proxida-
tive content of 5.2 mg per kg of food daily due to an increase in lipid perox-
idation (the primary cause of cell damage) and the activity of glutathione,
catalase, and superoxide dismutase (SOD), endogenous cancer prevention
agents [71]. Additionally, mice poisoned with carbon tetrachloride (CCl4)
and given food containing 30 mg of fucosterol per day for seven consecu-
tive days showed a notable drop in blood transaminases and an increase in
free radicals. SOD, catalase, and glutate peroxidation are retaining proteins
that are individually 33.89%, 21.56%, and 39.34% [56].
13.3.10 Antidiabetic
A characteristic complexity of diabetes mellitus is diabetic retinopathy
(DR). The underlying cause of the vision loss associated with this condi-
tion is close to the oxidative damage inflicted by high glucose levels on
the epithelial cells of the retinal pigment epithelium (RPE). In RPE cells,
superoxide dismutase (SOD) is thought to be the primary protective pro-
tein against oxidative damage. In addition, RPE cells are protected from
oxidative damage by the tripeptide glutathione (GSH), which is present in
RPE cells. Therefore, it is crucial to protect RPE cells by maintaining ade-

quate centralizations of SOD and GSH as molecules in order to protect the
retina from oxidative damage. A layer of retinal cells known as EPR plays
a significant role in the development and regulation of photoreceptors in
the retina of vertebrates. RPE cells function as a vehicle and capacity for
materials in the typical retina, including retinadeide, phagocytosis sepa-
rated from the external photoreceptor sections, light-blocking attempts,
the elimination of free radicals, the union of cytokines, and the develop-
ment of the retinal blood hindrance [26]. To maintain the integrity and
proper functioning of the human retina, the reliability of the EPR is crucial
[92]. RPE cells are typically isolated in the G1 stage after being refreshed
and sorted. RPE cells release SOD and GSH as a protective measure in
response to oxidative damage [47].
13.3.11 Different Biomedical Activities

Numerous researchers have discovered that phytosterols derived from
microalgae have antibacterial and anti-diabetic effects. The second
most frequent cause of death in humans is tuberculosis, which is conta-
gious and spread through the air. Sasikala Prakash [73] Microalgal iso-
chrysis galbana (ergost-5-en-3-ol and cholest-5-en-24-1,3-derived from
24-oxocholesterol) (with acetyloxy) Amikacin at a concentration of 50
g per ml, 200 g per ml with pyraminamide, and rifambicin at a concen-
tration of 40 g per ml are safe anti-tuberculosis medications in compar-
ison to other medications. Additionally, 0.5 g per ml disconnected from
earthy green growth. In a comparable study, sargassum ringgoldianum was
found to be as effective at suppressing M. tuberculosis H37Rv growth as
the anti-tuberculosis drug rifampicin. Microalgae Micromonas aff. pusilla
[88] and saringosterol both have unidentified natural actions. Diabetes is
a chronic illness that manifests as severe entanglements like high glucose
and hypoglycemia. Streptozotocin-induced antidiabetic effects in diabetic
mice have been observed in fucosterols contained in Pelvetia siliquosa
green growth. Additionally, a few microalgae species, such as Chrysoderma
sp. Additionally, Olisthodiscus luteus [59]; However, there is currently no
evidence to support the usefulness of these fucosterols.
The pharmaceutical industry has much more potential for phytosterols
[34] obtained from microalgae because of the high yearly microalgal lipid
yield. This is because it not only addresses the issue of growing global inter-
est, but it also provides increasingly popular alternatives due to the side
effects associated with manufactured medications.
13.4 Research Results on Well-Studied Algal Strains

Numerous studies on widely studied types of green growth bioactive
mixtures, such as Arthrospira, Botryococcus braunii, Chlorella vulgaris,
Dunaliella salina, Haematococcus pluvialis, and Nostoc, have been con-
ducted. These mixtures have been found to have antibacterial and anti-
viral properties as well as calming, fiery, anticoagulant, and antienzyme
properties. The extraction of bioactive mixtures from these microalgae is
the basis for these tests [26]. Because Nostoc includes proteins, minerals,
and unsaturated fats, it is used as a feedstock, pharmaceutical, and nutri-
tional supplement. The use of this bacterium in the treatment of fistulas
and some types of cancer regulates its clinical estimation [38]. Generally
speaking, Nostoc’s biomass has been recognized as a soothing agent and
has also been shown to aid in absorption, manage circulatory strain, and
strengthen the immune system. Cyanobine, a protein atom that Nostoc
species may transport, has shown promising results in the treatment of HIV
and influenza A(H1N1) [43]. Additionally, Nostoc species include polyun-
saturated unsaturated fats (PUFAs), which include basic unsaturated fats
as linoleic, -linolenic, -linolenic, octadecatetraenoic, and eicosapentaenoic
corrosive [53]. Basic unsaturated fats, which precede prostaglandins and
are extremely enthused by the pharmaceutical industry, are essential.
Chlorella is a very frequent green growth that has been discovered by
traditional Japanese ocean growth buyers, who frequently eat it and value it
as a dietary supplement. In addition to chlorophyll, proteins, and polysac-
charides, chlorella also includes 53% (w/w) protein, 23% (w/w) starches, 9%
(w/w) lipids, and 9% (w/w) lipid atomic segments. rich in essential amino
acids, minerals, and nutrients. The following components and 5% (w/w) of
minerals [35]. By adjusting the settings under which they develop, these
supplement focuses can be changed. The B12 complex is also rich in B12,
which is essential for platelet formation and recovery after injury. Chlorella,
like spirulina, has a GRAS certification from the FDA, which means that,
when grown in the right conditions and with the use of proper sanitation
and assembly procedures, it has the potential to influence human health. It
frequently serves as nourishment without being given [58].
Dunaliella is a single-cell, salt-tolerant green microalga that has received
significant attention for its potent pharmacological mixtures. Due to its
unique physiology, this microalgae is frequently regarded as an excep-
tional scenario with several biotechnological uses. Other bioactive mix-
tures, including as carotenoids, glycerol, lipids, chemicals, and minerals,
are abundant in Dunaliella. This microalgae is a substantial natural source
of beta-carotene and can produce up to 14% of its dry weight when grown
under supplement limitations, under salty, bright, and hot conditions [35].
In addition to P-carotene, this microalgae is abundant in proteins and fun-
damental unsaturated fats that can be consumed safely, as evidenced by the
recognition of GRAS. The biomass blends made from Dunaliella exhibit
a variety of natural properties, including hepatoprotective, antihyperten-
sive, bronchodilator, pain reliever, muscle relaxant, and anti-carcinogenic
effects. Additionally, microalgal biomass can be used directly in food and
pharmaceutical formulations [58]. Polysaccharides are a group of highly
valuable additives that have uses in the industries of medicine, food, cos-
metics, tissues, stabilizers, and emulsifiers [21]. Sulfated polysaccharides,
which are sulfate esters included in microalgal polysaccharides, offer
unique clinical applications [25, 26]. The activation and modification of
macrophages are essential for the therapeutic effect. The area, level of sul-
fation, and sugar synthesis of sulfur polysaccharides are used to identify
their natural movement [49].
According to some, microalgae are responsible for the antibacterial
properties of lipid fragments. The potential mix of compounds in micro-
algae, such as and -ionones, p-cyclotitral, neoplastic dienes, and phytol,
gives rise to their antibacterial properties. Escherichia coli, Pseudomonas
aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, -linole-
nic corrosive, eicosapentaenoic corrosive, and the lipid structure of micro-
algae hexadecatrienoic corrosive are a few examples of human pathogens
that exhibit antibacterial activity. This antibacterial property of microalgae
is due to the likely arrangement of mixtures, including phytol 55, neoplastic
dienes, and -ionone, and -cyclocitral. Pseudomonas aeruginosa, S. aureus,
E. coli -linolenic corrosive, eicosapentaenoic corrosive, hexadecatrienoic
corrosive, docosahexaenoic corrosive, palmitoleic corrosive, lauric corro-
sive, oleic, lactic corrosive, and arachidonic corrosive are all attributed to
antibacterial effect against human pathogens.
Carotenoids have a wide range of potential benefits for human health,
including the enhancement of waterfalls and the treatment of degenerative
diseases like macular degeneration. These mixtures function as anti-cancer
agents and lessen the oxidative damage caused by ROS. Studies have shown
that increased phenol use lowers the frequency of degenerative diseases.
Microalgae phenolic mixtures that can combat free radicals have been
identified [1].
Medicines play a vital role in enhancing the character of the population
and its future. Every year, enormous amounts of drugs are used in human
and veterinary medicine to cure illnesses, bacterial infections, stress, and
other disorders, prevent pregnancy, and promote the growth of aquaculture
and homesteads substance for waste water treatment. This is because to its
effectiveness in removing toxic elements from wastewater and potential for
natural goodwill [63].
13.5 Conclusion and Future Recommendations

This chapter has provided detailed information on the upcoming sections
on the most recent developments in the discovery of novel compounds
of pharmaceutical significance derived from algae, including bioactive
compounds, pharmacological significance of algae, antioxidative activ-
ity, antihypertensive activity, anticoagulant activity, antiproliferation
activities, immune-stimulant activity, cholesterol-lowering activity, anti-
inflammatory activity, anticancer activity, and cancer prevention.
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14
Applications of Algae in the Production
of Single-Cell Proteins and Pigments
with High Relevance in Industry
Juliana Bunmi Adetunji1*, Omowumi Oyeronke Adewale1,
Charles Oluwaseun Adetunji2 and Isreal Olu Oyewole1

1

2
Department of Microbiology, Biotechnology and Nanotechnology Laboratory,
Edo State University Uzairue, Edo State, Nigeria
Abstract
Algae serve as a source for diverse types of chlorophyll. It is a major constituent
of the ecosystem, specifically marine and freshwater habitats. Nutritionally, algae
have been established to have high protein content when compared to conven-
tional sources of protein. In industry, biotechnology tools have been used to pro-
duce many nutritional supplements from microalgae. Also, microbial dried cells
or biomass, also known as single-cell protein (SCP), were isolated from microalgae
like Chlorella, Spirulina, and Dunaliella, which are the most common ones. The
supplements produced from these algae have nutraceutical potential for diverse
health-related issues. The biomass consists of vitamins, lipids, minerals, carbohy-
drates, and proteins; and its cells also produce some amino acids useful for ani-
mal and human consumption. This chapter addresses the production of SCP from
microalgae and its application in the diet, along with highlighting some beneficial
pigments, like astaxanthin, fucoxanthin, carotenoid, etc., derived from algae and
their commercial application.
Keywords: Algae, single-cell proteins, pigments, industry, astaxanthin,
fucoxanthin and carotenoid pigments
343
14.1 Introduction
The scarcity of food and protein caused by the ever-increasing population
requires drastic measures to sustain future growth. Due to the this, there
is a need for an alternative novel protein source to meet the growth in
population. Hence, algae have been documented as resource-efficient and
natural protein feed and food constituents, known as single-cell protein
(SCP), to support those derived from bacteria and yeast microbes [1]. Over
the years, proteins have been sourced from animal-based products like
beef and turkey, which give an equivalent of 50–60% protein content [2].
Interestingly, proteins have also been derived from plant materials and as
such are referred to as vegetable proteins with a high nutrient composition
like fibers, minerals, vitamins, and antioxidants due to less environmental
value and increased sustainability when compared with the animal-based
proteins [3].
It was also documented that insects have served as an important protein
source with about 60% protein content on average; hence, insect farming
has led to a decrease in the ecological footprint as a result of its low impact
on deforestation, soil fertility, and water content [4]. Moreover, there is
evidence that algae food and feed products can be developed commercially
because they’re natural and have health benefits resulting from the vari-
ety of nutrients and bioactive constituents present in them [5]. It was also
documented that algae biomass serves as a sustainable protein source with
a high protein content of about 70% of microalgae. Bleakley and Hayes
documented that close to 47% of specific red seaweed species have high
protein levels compared to other seaweeds in which the protein level is
usually between 9–22% [6]. The authors also considered microalgae as a
feasible protein source with diverse essential amino acids of interest similar
to those present in animal protein [7, 8].
Consequently, algae which serve as protein derived from vegetables
have numerous nutrients and biologically active constituents that support
nutraceutical food products. Algae cultivation is mostly performed on
small land from agricultural byproducts to support the circular economy.
De Mendonça et al. documented that alga can extract carbon dioxide in
about 10 to 50 times greater amounts than the plants on land, thus it serves
as a potential food source [9].
Algae contain low protein digestibility like a whole cell or single-cell
protein in their unprocessed form because the composition and structure
of the cell wall consists of a high percentage of fibers and polyphenols
[10]. Moreover, the single cell protein (SCP) is an alternative source of the
Single-Cell Proteins and Pigments from Algae 345
traditional protein derived from animal feeds, without any adverse effects
on humans [11].
14.2 Microalgae-Derived Single Cell Protein (SCP)

Single cell proteins are dried cell bioprotein derived from organisms like
algae, fungi, yeast, and bacteria. Reports have shown that fungi and bac-
teria have great potential in producing high protein content as a result of
their chemical structure composition. However, carbohydrates, nucleic
acids, fats, minerals, and vitamins have also been documented to contain
high protein components, and hence could serve as SCP with high essen-
tial amino acids such as lysine, methionine, and threonine. It is essential to
research an alternative for protein replacement due to the expensive nature
of the available protein from sources like soybeans and fish. Reports have
shown that SCP is a dietary product of high quality derived from wastes
[12].
This alternative source of protein is documented to have a less det-
rimental effect. However, the focus for over a decade now has been the
exploration of single-product from microalgal while the biomass-derived
after extraction could also be used for valorization [13]. Microalgae like
Chlorella and Spirulina with low protein and lipids production are also
utilized in higher-value production of pigments, fatty acids, and phycocy-
anin. Besides which, Bratosin et al. documented that SCP contains other
macro- and micronutrients like lipids, minerals, nucleic acid, carbohy-
drates, vitamins, and other major amino acids [11]. The SCP serves as a
significant substitute for proteins derived from food sources like fish and
soybean products that are extremely expensive.
In 2022, Janssen et al. established that the protein content of microalgae
is much higher than that of chicken, peanuts, soy flour, skimmed milk,
and fish [14]. Though Dunaliella, Galdieria, and Spirulina are exceptional,
Galdieria shows high sulfur-containing essential amino acid contents.
Bogale documented that SCP derived from microorganisms are mainly
from dead cells, dry microbial cells as well as total proteins isolated from
pure microbe cell culture from numerous microorganisms like filamen-
tous fungi, yeast, and algae that serve as an alternative protein source for
animals and humans [15]. However, microorganisms make use of waste
and cost-effective feedstock as the carbon energy source for their growth
to release protein concentrate, biomass, or amino acids. This becomes
necessary due to the hike in the world population and shortage of pro-
tein worldwide, which could eventually lead to nutrient deficiency. It was
stated that SCP provides a very promising protein source that can satisfy
the world shortage of food while the population increases, by using diverse
energy sources for the growth of the microorganism [16]. For many years,
the nutritional supplements derived from microalgae have been the major
focus of microalgal biotechnology research. The biomass of Spirulina,
Dunaliella, and Chlorella have great commercial value [17] and are often
used as nutraceuticals due to their numerous health benefits. SCP contains
mainly proteins, vitamins, lipids, carbohydrates, minerals (trace minerals),
and salts because the cells can generate all essential amino acids useful to
man and animals.
Najafpour stated that large algae, being a source of SCP, have promising
potential for protein supplements for the world’s food shortage due to the
ever-increasing population [16].
Most single cell-derived proteins are commonly from microalgae
Chlorella Vulgaris or Arthrospira platensis [18]. However, it was established
that diverse species of microalgae are often whole cells, but as of today,
the EU has documented that to attain a substantial position with other
developed nations in the development of microalgae-based food and feed
sector, it is essential to maximize protein volume and content production,
reduce the cost of production and also there must be a high range of EFSA-
approved microalgae suitable for food applications [18, 19].
14.2.1 Dunaliella
Microalgae like Dunaliella have been identified as a natural protein source
as far back as the 1950s; it has numerous applications, particularly as feed,
high-value products, and food for humans [20]. The algae Dunaliella
also produce a unique β-carotene that is commercially relevant through
the process of hypercarotenogenesis [21]. The process of hypercaroteno-
genesis from dried biomass of Dunaliella started in the 80s in countries
like the USA, Israel, Australia, and later China and India joined the β-
carotene production process from microalgae [21]. In the US, Dunaliella
is claimed to be Generally Regarded as Safe (GRAS) by the US Food and
Drug Administration (FDA) for cosmetic products, animal and human
nutrition, and food coloring [20].
Dunaliella biomass protein content and composition were performed
using a snapshot approach under strict conditions and specific growth
stages [1]. The assessment revealed that 50–80% protein is present in the
dried biomass of Dunaliella [1, 22]. The Dunaliella microalgae do not have
rigid cellulosic cell walls, and as such, animals and humans digest it readily.
Gifuni et al. reported the co-production of microalgae with protein and

vitamin nutritional benefit derived from Dunaliella [13]. Dunaliella bio-
mass protein can be improved through the co-production of functional
proteins resulting in high digestibility protein, and carotenoids with col-
oring, immune-stimulating, and antioxidant functions embedded in prod-
ucts like poultry, ornamental fish feed, feed, pet food, and ornamental bird
feed [23].
14.3 Applications of SCP in Diets

Application of the derived SCP from microalgae depends on minerals,
nucleic acid, enzymes, vitamins, and amino acids composition, which
complements the relatively cheap protein content when compared to that
from animals and some plant sources [24]. Meanwhile, the amino acid
profiles are excellent, which contributes to their nutritional acceptability
to conventional protein sources [25]. Algae produce about 40% SCP after
processing, which supports the findings of Ferreira et al. that the essential
amino acids present in microbes are determined by the growth media and
the substrate utilized [26]. Interestingly, bacterial and yeast microorgan-
isms replicate within a short period of 5–15 min but for algae and mold
species their replication is between 2–4 h. Nasseri et al. also documented
that due to the fast-growing rate of microorganisms yielding a large quan-
tity of biomass from algae within 3–6 h, bacteria: 30 min to 2 h, yeast: 40
min to 3 h [17]. Cyanocobalamin (B12) vitamin has been reported to be
abundant in algae and bacteria while other vitamins in SCP include pan-
tothenic acid (B5), thiamine (B1), pyridoxine (B6), riboflavin (B2), niacin
choline, folic acid (B9), para-aminobenzoic acid, inositol and biotin (B7)
[27]. Also, the production processes do not depend on the climatic and
environmental conditions contributing to its availability throughout the
year [28].
Also, Banach et al. have reported on the inclusion of macroalgae in the
human diet for years, and as such more macroalgae have been approved by
EFSA [29]. However, the production in Europe is far less than that obtain-
able in Asia. Meanwhile, macroalgae provide an essential component of
the Asian diet due to their protein composition, which includes Porphyra
tenera (44%), Chondrus crispus (20%), Ulva lactuca (29%), Undaria pinnat-
ifida (29%), Palmaria palmata (19%), and Fucus serratus (17%). The grow-
ing interest in algae-containing products has, however, triggered the EU’s
effort to increase the cost-effective production of cultivated macroalgae,
instead of harvested ones, to boost their incorporation in food and feed

markets and to improve their food safety [19, 30].
14.4 Pigments Derived from Algae

14.4.1 Astaxanthin
In 2010, Dragos et al. reported that most red-colored pigments seen in
most marine organisms and freshwater are derived from astaxanthin and
have great benefits to human and aquaculture health [31]. It was docu-
mented that green microalgae called Haematococcus pluvialis could accu-
mulate high quantities of astaxanthin during a stress condition. Dragos and
co-author performed an experiment in 2010 that established that astaxan-
thin synthesis induced via a change in light intensity through increased
irradiance coupled with continuous illumination, resulted in algal bio-
mass astaxanthin content approximated to be 5.7 mg · g -1 per dry biomass.
Under light stress conditions, the biomass composition was significantly
changed, and increased the astaxanthin content by approximately 10 times
along with a decrease of protein amount and increase of carbohydrates
content [30].
Raza et al. documented that astaxanthin (AST), a known red pigment
of carotenoid, provides the high-quality keto-carotenoid pigment used in
livestock, therapeutics, food, and nutraceuticals [31]. Astaxanthin could be
sourced from algae but other sources include crustaceans, fish, and birds. It
is of great benefit in animal nutrition when used as a pharmaceutical agent.
Astaxanthin was also reported to have several biological properties which
include anticarcinogenic, antihypertensive, antioxidant, and anti-obesity.
Both humans and animals have also used astaxanthin as an immunomod-
ulator in health sustainability [31].
14.4.2 Fucoxanthin
Fucoxanthin is a xanthophyll pigment in most micro and macro marine
algae. Moreover, brown macroalgae belonging to the Phaeophyceae family
have been established to be the key source of fucoxanthin (a chloroplast
accessory pigment responsible for its observed colour).
Consequently, species of microalgal like Dunaliella salina, Spirulina platen-
sis, Haematococcus pluvialis, Chlorella spp., Scenedesmus spp., Chlorococcum
spp., Nannochloropsis spp., and Botryococcus braunii were reported to have
abundant carotenoid that is applied in nutraceutical, food, pharmaceutical
products and feed [32]. Gupta et al. stated that carotenoid antioxidants
and green cell photoprotector production can be scaled up in algae using
light-harvesting apparatus [33]. Moreover, phycocyanin, a natural blue pig-
ment used in food and cosmetics, are products of eukaryotic algae, cryp-
tophytes, rhodophytes, and cyanobacterium, which are mostly used as
colorants due to the lack of natural stable blue pigment in nature [34, 35].
14.4.3 Carotenoids
Carotenoids are lipophilic pigments found in plants and algae. Moreover,
the novel microalga Chlorococcum sp. is a target candidate for the pro-
duction of high-value carotenoid phytoene with cosmeceutical, nutraceu-
tical, and pharmaceutical applications [34]. In 2019, Laje and colleagues
conducted a study on the reduction of phytoene desaturase (PDS) activity
with the pigment-inhibiting herbicide 1-methyl-3-phenyl-5-[3-(trifluo-
romethyl)phenyl]pyridin-4-one (fluridone), that caused excess accumu-
lation of phytoene in the characterized microalgal strain Chlorococcum
sp. (UTEX B 3056). After post-incubation with fluridone, phytoene levels
were measured at ~33 ug/mg cell tissue, as opposed to non-detectable lev-
els in control cultures.
14.5 Conclusion
Single cell proteins derived from algae have proven to have higher protein
content than the conventional protein sources, and hence could serve as an
alternative source of protein to feed the ever-increasing population. Also,
the pigments isolated from algae have also provided some beneficial sup-
ports to the food and pharmaceutical industries.
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Index
Additives, 95, 96, 105, 107, 110 Antioxidant action, 20

Agars, 7 Antioxidant activity, 267, 268
Algae, 95–97, 99–107, 109–111, 113, Antiproliferative, 144
115–118, 140, 322, 324 Antiprotozoal action, 19
Algae and cyanobacterial constituents Antipsychotic treatment, 130
with potential biological action, Antiviral action, 24
12–15 Apoptosis, 204, 207, 215
Algae metabolites, 286 Apoptotic, 144
lipids, 286, 288 Asexual reproduction, 141
polysaccharides, 298, 301, 302, 307 Astaxanthin, 198, 213, 216, 236
proteins, 287, 288, 290, 292, 296 Astrocytes, 201, 208
Algae respiration, 141 Atherosclerosis, 229
Algae-based biopolymer, 147 Autoimmune disease, 129, 146
Algal, 198, 203
Alginate, 204–205, 258, 259 Beta oxidation, 131, 132
Amino acids, 343–347 Beta-cryptoxanthin, 237
Amphipathic properties, 125 Bioactive compounds, 322, 334
Animal protein, 344 Bioactive compounds from
Antiarrhythmic properties, 127 cyanobacteria, 51
Antibacterial action, 15 Bioactive constituents, 2–4, 6, 7, 11, 15
Antibacterial properties, 269–271 Bioactive metabolites, 287, 295
Antibiotics, 9 Bioactive substances, 11
Anticancer action, 21 Biocomposite, 141
Anticancer activity, 289, 295 Biodegradation, 140
Anticarcinogenic, 146 Bioethanol, 203
Anticoagulant action, 25 Biofuel, 2, 4, 140, 286, 294
Antidiabetic activity, 146 Biomass, 344
Antifungal action, 17 Biomolecules, 125
Antifungal activity, 269 carotene, 286, 287, 303
Antiherpetic, 210 lutein, 286, 287
Anti-inflammatory, 139, 144, 147 oleic acid, 286, 287
Anti-inflammatory action, 18 phycocyanin, 287, 295, 296, 302
Antineoplastic action, 21 Bioprospecting for new algae, 4
353
354 Index
Bioremediation, 140 Eicosapentaenoic acid, 132

Biosynthesis and biological activities, 11 Endothelial cells, 128
Bipolar depression, 130 Environmental, 147
Brown seaweed polysaccharides, 256, Extraction methods, 9
257 advantages of new extraction
techniques, 10
Cancer, 224–226, 236, 237 microwave, 9
Carrageenan, 259, 260 polyunsaturated fatty acids
Cell proliferation, 130, 147 (PUFAs), 11
Chlorella, 6, 12, 26 solid–liquid extraction, 10
Chlorophyta, 3, 6, 8 supercritical fluid extraction, 9
Cholesterol, 199, 209, 213–214 techniques, 9
Circular economy, 147 Extrusion, 143
Compounds with anticarcinogenic, 161
anticarcinogenic activities, 168 Features of microalgae,
chlorophyll, 163–164 157–158
eicosapentaenoic acid (EPA), Food and drug administration, 5
165–166 Food industry, 88
fucoxanthin, 166–167 Fossil fuel, 286, 287
monogalactosyl glycerols, 168 Fractions of microalgae species with
nonyl 8-acetoxy-6-methyloctanoate anticancer properties, 158
(NAMO), 167 Amphidinium carterae organic
other active compounds from fractions, 159
microalgae, 168 Canadian marine microalgal pool
phycocyanin, 163 aqueous extract, 160
polysaccharides, 161–162 carotenoid-rich extracts of chlorella
polyunsaturated aldehydes (PUAs), species, 158–159
164 Chaetoceros calcitrans ethyl acetate
stigmasterol, 166 and ethanol extracts, 159
violaxanthin, 164–165 Chlorella sorokiniana aqueous
Compression modelling, 142 extract, 161
Cosmetics and personal care, 87 methanolic extracts from
Current trends in the design of wound amphidinium carterae, 160
dressing, 253–256 Skeletonema marinoi hydrophobic
Cyanobacteria, 2, 3, 5–7 fraction, 160
Cyanobacterial constituents, 12 Fucoidan, 197–202, 212, 216–217, 257,
Cytotoxic, 143 258
Fucosterol, 197, 204
Diabetes mellitus, 228 Fucoxanthin, 228, 229, 232,
Dinoflagellates, 3, 8 235–238
Dopaminergic pathway, 129 Functional groups, 142
Index 355
Gastrinoma (Zollinger-Ellison Microalgae with anti-inflammatory

syndrome), 181 activity, 81
antiulcer products developed from Microalgae with bioactive compounds,
algae, 184 44
natural products used in the chlorella, 47
treatment of peptic ulcer, 183 dunaliella, 50
treatment using synthetic medicine, nostoc, 49
181–183 spirulina, 46
Glucanase, 203 Microalgae with immunomodulatory
Glycoside hydrolases, 203 activity, 82
Green growth, 322–327, 329, 331, 332 Microbial cell, 345
Green seaweed polysaccharides, 260, Microorganisms, 8
261
Nanocomposite, 142
Hemostatic activity, 263, 264 Nanoformulation, 128
Hydrophilic, 126 Natural bioactive components, 8
Hydrophobic, 126 Natural fiber, 143
Hypertension, 228 Neoplasm (cancer), 3, 6, 23
Hypolipidemic, 147 Neuroinflammation, 131, 145
Immunomodulatory, 146 Nuclear magnetic resonance (NMR), 8
Immunomodulatory and anti- Nutraceutical, 343–344, 346, 348–349
inflammatory effects, 264–267 Nutrient, 344–345
Immunosuppressive action, 25
Inflammation, 129 Obesity, 232, 233
Injection molding, 143 Omega-3 polyunsaturated fatty acid,
128
Laminarin, 197, 202–204 Operational cost, 147
laminarinase, 203
Lipid metabolites, 131 Peroxisomal disorder, 131
Lipoproteins, 131 Phaeodactylum tricornutum, 127
Liquid chromatography–mass Phaeophyta, 3, 4
spectrometry (LC-MS), 8 Pharmaceutical applications of
Lutein, 237 microalgae, 66
anticancer properties, 67
Mechanisms underpinning the wound anti-inflammatory properties, 70
healing effects of algae, 261, antimicrobial properties, 69
262 antioxidant properties, 70
Microalgae, 3, 4, 6, 8–10, 12–15, 18, antiviral properties, 69
21–23, 26, 198, 217, 220–221, cardioprotective properties, 66
323, 324, 326, 328–333 Pharmaceutical industry, 87
Microalgae anticancer activity, 85 Pharmaceuticals, 322, 323, 331–334
356 Index
Phycocolloids, 186–187 Saproxanthin, 238

agar, 187 Seaweed, 198–199, 216, 218, 220
alginates, 186–187 Secondary metabolites from
carrageenans, 187 microalgae, 55
fucoidan, 188 carotenoids, 55
laminaran, 190 β-carotene, 55
ulvans, 189 astaxanthin, 57
xylan and porphyran, 191–193 fucoxanthin, 59
Phycocyanin, 209 violaxanthin, 59
Phycoerythrin, 197, 208 zeaxanthin and lutein, 58
Phytoplankton, 2, 3, 15 Single cell protein, 344–349
Polymeric composite, 143 Siphonaxanthin, 233, 238
Polyphenols, 344 Sources of microalgae, 158
Polyunsaturated fatty acids, 60 Spirulina, 6, 7, 12, 15, 16, 21, 24, 25
Porphyridium cruetum, 127 Symptoms of peptic ulcer disease, 181
Post-traumatic stress disorder, 129 anxiety, 181
Potential of microalgae in quality diet and alcohol, 181
enhancement of natural products, genetic variable, 181
87 hypercalcemia, 181
Progression, predisposing factors and smoking, 181
treatment of cancer, 156 Synaptogenesis, 131
cancer progression, 156
predisposing factors to cancer, Therapeutic, 198, 201, 204, 209, 216
157 Thermoforming, 143
treatment of cancer, 157 Tyrosine, 215
Proteins and polypeptides, 61
Vasculopathies, 128
Receptor, 201, 206–207
Red pigment, 348 Wound-healing property of algae and
Red seaweed polysaccharides, 260 cyanobacteria, 271–273
Rhamnose, 199
Rhodophyta, 3 Zeaxanthin, 237, 238
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Next-Generation Algae

Volume II: Applications in Medicine

Wiley Global Headquarters

Limit of Liability/Disclaimer of Warranty

Library of Congress Cataloging-in-Publication Data

Cover image: Pixabay.Com

Printed in the USA

2.3 Microalgae with Potential for Obtaining

4 Application of Astaxanthin and Carotenoids Derived

5.7 Challenges and Issues of Production and Use

Coolia Malayensis, Ostreopsis Ovata, Amphidinium

9 Pharmacological and Antioxidant Attributes of Significant

10.2.12 Obesity 232

12 Application of Nanotechnology for the Bioengineering

13.2 Bioactive Compounds 323

The application of both micro and macroalgae has been recognized as a

of polyunsaturated fatty acids (PUFAs) and its biomedical applications,

Charles Oluwaseun Adetunji

*Corresponding author: [email protected]

Keywords: Algae, biologically active compounds, therapeutic activities

A surprising amount of agar is produced by algae in intertidal and shal-

1.2 Microalgae-Derived Natural Products

Microalgae produce biocompounds by utilizing light energy along with

1.3 Bioprospecting for New Algae

1.4 Therapeutically Essential Natural Products

(including B12), Spirulina sp. is a wonderful abundant source of potas-

1.5 Screening for Bioactive Constituents

of data to elaborate a better understanding of different cellular processes

As per the current scenario on the non-selective and unsystematic

1.6 Extraction Methods

therapeutically active constituents. Moreover, this type of extraction

• Animals (feed additives),

1.7 Biosynthesis and Biological Activities

amounts in foods. A variety of bioactive substances appear to provide

1.7.1 Antibacterial Action

alkenes, cyclic polysulfide and halogenated ketones [87]. Furthermore,

fraxinifolia [97], were found to have antimicrobial efficacy towards MRSA

1.7.2 Antifungal Action

A. albicans, Aspergillus niger and others. When tested against Aspergillus

1.7.3 Anti-Inflammatory Action

various cyanobacterial polysaccharides is responsible for the activation of

1.7.4 Antiprotozoal Action

efficacy against the parasite, so they might replace antibiotic medications

1.7.5 Antioxidant Action

nutraceuticals.” It is possible to prevent oxidative damage in cells caused by

1.7.6 Antineoplastic (Anticancer) Action

Cyclopeptide cryptophycin produced by Nostoc also has demonstrated

nearly forty percent of worldwide economic output. Microalgal bloom nat-

order to determine their effectiveness. Studies in this area will provide

1.7.7 Antiviral Action

properties [165]. As an example, carrageenan, a compound derived from

1.7.8 Anticoagulant Action

1.7.9 Immunosuppressive Action

8. Ferreira S. P., SoaresL.A., and CostaJ.A., Microalgas:uma fonte alternativa na

marine resources: Macro and micro algae, cyanobacteria, and invertebrates.

virus-inactivating protein that binds viral surface envelope glycoproteing

114. Schepetkin, I. A., and Quinn, M. T. Botanical polysaccharides: Macrophage

Faculty of Pharmacy, Raja Balwant Singh Engineering Technical Campus,

Bichpuri, Agra, India

lipoprotein (LDL) cholesterol while increasing the production of high-

to gradually reduce the moisture content of the microalgae,