Ijms 24 02098

International Journal of
Molecular Sciences
Review
Moringa oleifera: An Updated Comprehensive Review of Its
Pharmacological Activities, Ethnomedicinal,
Phytopharmaceutical Formulation, Clinical, Phytochemical,
and Toxicological Aspects
Ashutosh Pareek 1, * , Malvika Pant 1 , Madan Mohan Gupta 2 , Pushpa Kashania 1 , Yashumati Ratan 1 ,
Vivek Jain 3 , Aaushi Pareek 1 and Anil A. Chuturgoon 4, *
1 Department of Pharmacy, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India

2 School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies,
St. Augustine 3303, Trinidad and Tobago
3 Department of Pharmaceutical Sciences, Mohan Lal Sukhadia University, Udaipur 313001, Rajasthan, India
4 Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences,
University of KwaZulu-Natal, Durban 4041, South Africa
* Correspondence: [email protected] (A.P.); [email protected] (A.A.C.)
Abstract: Moringa oleifera, also known as the “tree of life” or “miracle tree,” is classified as an im-
portant herbal plant due to its immense medicinal and non-medicinal benefits. Traditionally, the
plant is used to cure wounds, pain, ulcers, liver disease, heart disease, cancer, and inflammation.
This review aims to compile an analysis of worldwide research, pharmacological activities, phyto-
chemical, toxicological, and ethnomedicinal updates of Moringa oleifera and also provide insight into
its commercial and phytopharmaceutical applications with a motive to help further research. The
Citation: Pareek, A.; Pant, M.; Gupta, scientific information on this plant was obtained from various sites and search engines such as Scopus,
M.M.; Kashania, P.; Ratan, Y.; Jain, V.; Pub Med, Science Direct, BMC, Google Scholar, and other scientific databases. Articles available in
Pareek, A.; Chuturgoon, A.A. the English language have only been referred for review. The pharmacological studies confirm the
Moringa oleifera: An Updated hepatoprotective, cardioprotective, and anti-inflammatory potential of the extracts from the various
Comprehensive Review of Its plant parts. It was found that bioactive constituents are present in every part of the plant. So far,
Pharmacological Activities,
more than one hundred compounds from different parts of Moringa oleifera have been characterized,
Ethnomedicinal,
including alkaloids, flavonoids, anthraquinones, vitamins, glycosides, and terpenes. In addition,
Phytopharmaceutical Formulation,
novel isolates such as muramoside A&B and niazimin A&B have been identified in the plant and
Clinical, Phytochemical, and
have potent antioxidant, anticancer, antihypertensive, hepatoprotective, and nutritional effects. The
Toxicological Aspects. Int. J. Mol. Sci.
2023, 24, 2098. https://doi.org/ traditional and nontraditional use of Moringa, its pharmacological effects and their phytopharma-
10.3390/ijms24032098 ceutical formulations, clinical studies, toxicity profile, and various other uses are recognized in the
present review. However, several traditional uses have yet to be scientifically explored. Therefore,
Academic Editor: Debasish
further studies are proposed to explore the mechanistic approach of the plant to identify and isolate
Bandyopadhyay
active or synergistic compounds behind its therapeutic potential.
Received: 29 November 2022
Revised: 9 January 2023 Keywords: Moringa oleifera; traditional medicinal uses; pharmacological activity; phytochemistry;
Accepted: 13 January 2023 phytopharmaceutical formulation; toxicity
Published: 20 January 2023
1. Introduction
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland. Moringa oleifera (M. oleifera), the “miracle tree”, thrives globally in almost all tropical
This article is an open access article and subtropical regions, but it is believed to be native to Afghanistan, Bangladesh, India,
distributed under the terms and and Pakistan [1]. The Moringa family comprises 13 species (M. oleifera, M. arborea, M. rivae,
conditions of the Creative Commons M. ruspoliana, M. drouhardii, M. hildebrandtii, M. concanensis, M. borziana, M. longituba,
Attribution (CC BY) license (https:// M. pygmaea, M. ovalifolia, M. peregrina, M. stenopetala), of which M. oleifera has become well
creativecommons.org/licenses/by/ known for its use in nutrition, biogas production, fertilizer, etc., [2,3]. Moringa has the
4.0/). unique property of tolerating drought [3]. Studies have shown that M. oleifera is among the
Int. J. Mol. Sci. 2023, 24, 2098. https://doi.org/10.3390/ijms24032098 https://www.mdpi.com/journal/ijms

Int. J. Mol. Sci. 2023, 24, 2098 2 of 36
cheapest and most reliable alternatives for good nutrition [4]. Nearly all parts of the tree
are used for their essential nutrients. M. oleifera leaves have a high content of beta-carotene,
minerals, calcium, and potassium [5]. Dried leaves have an oleic acid content of about 70%,
which makes them suitable for making moisturizers [6]. The powdered leaves are used
to make many beverages, of which “Zija” is the most popular in India [7]. The bark of
the tree is considered very useful in the treatment of different disorders such as ulcers [8],
toothache [9], and hypertension [10]. Roots, however, are found to have a role in the
treatment of toothache [9], helminthiasis [11], and paralysis [12]. The flowers are used to
treat ulcers, enlarged spleen, and to produce aphrodisiac substances [2]. The tree is believed
to have incredible properties in treating malnutrition in infants and lactating mothers [3].
The present review aims to sum up the updated insight regarding the pharmacological
activities, worldwide research analysis, toxicological, phytochemical, and ethnomedicinal
properties of M. oleifera.
2. Material Method
2.1. Article Eligibility Criteria
In the framework of searching for study material, the following keywords were used:
“Moringa oleifera”, “pharmacology M. oleifera”, “phytochemistry M. oleifera”, “ethnobotanical
applications M. oleifera”, “toxicology M. oleifera”, and other combinations of terms such as
biochemical constituents, taxonomic classification, geographical distribution, and plant
formulation to search relevant peer-reviewed journals in various scientific databases such
as Scopus, PubMed, Springer, Google scholar, and Wiley. Articles available in the English
language have only been referred for review. Articles were analyzed by reading the title
and abstracts of the articles found, which clearly indicated that they were all relevant.
2.2. Software and Techniques Used

Chemical structures identified in the plants were searched in the Webbook, Chemspi-
der, and PubMed databases, and at the same time, the identified structures were drawn
using Chem Draw (version 12.0.2). VOS Viewer software (1.6.18) was used to generate the
map of global collaboration between countries. Global country boundaries (GIS layers)
were obtained from an open-source web platform (DIVA-GIS) for geographic mapping.
Spatial techniques were used with ArcGIS 10.1 to map M. oleifera indigenous and introduced
countries and research activities in each country.
3. Worldwide Research and Collaboration

A country-specific research database on M. oleifera was extracted from Scopus, and the
data were linked directly to the country shapefile using the “connect field” function in the
GIS environment for geospatial mapping. The analyses revealed that scientists from about
15 countries had published more than 100 research papers during the period 2000–2022.
Among which India was the most prolific country (n = 1083), followed by Nigeria (n = 441),
Brazil (n = 383), Egypt (n = 361), China (n = 331), Indonesia (n = 327), Pakistan (n = 281),
South Africa (n = 272), Malaysia (n = 260), the United States (n = 214), Saudi Arabia
(n = 205), Mexico (n = 163), Thailand (n = 127), and Italy (n = 105), (Figure 1).
International studies on M. oleifera involve the collaboration of scientists from countries
such as India, China, Egypt, Saudi Arabia, Cuba, Australia, the United States, Nigeria, and
Portugal, which is indicated by circles in the map (Figure 2). The analysis shows that many
articles were published in the past decade, indicating the growing interest of researchers in
this plant worldwide.
Int.
Int. J.J.Mol.
Mol. Sci.
Sci.2023,
2023, 24,
24, x2098
FOR PEER REVIEW 3 of
3 of 3638
Int. J. Mol. Sci. 2023, 24, x FOR PEER REVIEW 4 of
Figure 1. ArcGIS
Figure ArcGIS 10.1-based
10.1-basedspatial
spatialdistribution
distributionmap
maphighlights
highlightsresearch
researchpapers
paperspublished
publishedononM.
oleifera worldwide. A spatial technique was used to generate a map, and GIS layers wereobtained
M. oleifera worldwide. A spatial technique was used to generate a map, and GIS layers were obtained
from DIVA-GIS, an open-source web platform.
from DIVA-GIS, an open-source web platform.
International studies on M. oleifera involve the collaboration of scientists from coun-

tries such as India, China, Egypt, Saudi Arabia, Cuba, Australia, the United States, Nige-
ria, and Portugal, which is indicated by circles in the map (Figure 2). The analysis shows
that many articles were published in the past decade, indicating the growing interest of
researchers in this plant worldwide.
Figure2.2.Network
Figure Network visualization of international
visualization collaborative
of international research conducted
collaborative for M. oleiferafor
research conducted using
M. oleifera u
VOS viewer
ing VOS (1.6.18).
viewer (1.6.18).
4. Taxonomical Classification
The plant M. oleifera belongs to the Kingdom: Plantae; Sub kingdom: Tracheobionta;
Super division: Spermatophyta; Division: Magnoliophyta; Class: Magnoliopsida; Sub
Int. J. Mol. Sci. 2023, 24, x FOR PEER REVIEW 5 of 38
4. Taxonomical Classification
Int. J. Mol. Sci. 2023, 24, 2098 The plant M. oleifera belongs to the Kingdom: Plantae; Sub kingdom: Tracheobionta;
4 of 36
Super division: Spermatophyta; Division: Magnoliophyta; Class: Magnoliopsida; Sub
class: Dilleniidae; Order: Capparales; Family: Moringaceae; Genus: Moringa; Species:
oleifera
class: [3,13,14]. Order: Capparales; Family: Moringaceae; Genus: Moringa; Species:
Dilleniidae;
oleifera [3,13,14].
5. Morphology
5. Morphology
The tree grows rapidly in loamy and well-drained sandy soils, preferring a height of
500 mThe tree sea
above grows rapidly
level in loamy the
[1]. Normally, andtree
well-drained
is small tosandy
mediumsoils,
in preferring a height
size, the leaves are
of
naturally trifoliate, the flowers are born on an inflorescence 10–25 cm long [14], and are
500 m above sea level [1]. Normally, the tree is small to medium in size, the leaves the
naturally
fruits are trifoliate, the flowers
usually trifoliate and are born on referred
commonly an inflorescence 10–25[3].
to as “pods” cm The
longtrunk
[14], and the
usually
fruits
growsare usually
straight buttrifoliate and commonly
is occasionally referred
poorly formed, thetobranches
as “pods”are[3]. The trunk
usually usually
disorganized,
grows straight
the canopy but is occasionallythe
is umbrella-shaped; poorly
brownformed,
seeds the
havebranches are usuallyhull,
a semi-permeable disorganized,
and each
the
treecanopy is umbrella-shaped;
has a capacity the brown seeds
of about 15,000–25,000 seeds have a semi-permeable
per year [10]. hull, and each tree
has a capacity of about 15,000–25,000 seeds per year [10].
6. Botanical and Geographical Distribution
6. Botanical and Geographical Distribution
M. oleifera is widely distributed worldwide, but its indigenous origin is in India, Ara-
M. oleifera is widely distributed worldwide, but its indigenous origin is in India,
bia and the East Indies. It is common in Asia, Africa, the Caribbean, Latin America, the
Arabia and the East Indies. It is common in Asia, Africa, the Caribbean, Latin America,
Pacific Islands, Florida, Madagascar, Central America, Cuba, the Philippines, Ethiopia,
the Pacific Islands, Florida, Madagascar, Central America, Cuba, the Philippines, Ethiopia,
and Nigeria [2,15]. The history of the plant explains that M. oleifera was introduced from
and Nigeria [2,15]. The history of the plant explains that M. oleifera was introduced from
India to Africa, Southeast Africa, and the Philippines in ancient times [16,17] (Figure 3). It
India to Africa, Southeast Africa, and the Philippines in ancient times [16,17] (Figure 3). It
requires tropical and subtropical regions and grows at a temperature of about 25–35 °C
requires tropical and subtropical regions and grows at a temperature of about 25–35 ◦ C [1].
[1]. M. oleifera is a deciduous type of tree typically grown in tropical and subtropical re-
M. oleifera is a deciduous type of tree typically grown in tropical and subtropical regions
gions across the globe [18,19]. It grows best in indirect sunlight and without waterlogging,
across the globe [18,19]. It grows best in indirect sunlight and without waterlogging, and
and the soil should be slightly acidic to alkaline. The tree begins to bear fruit at 6 to 8
the soil should be slightly acidic to alkaline. The tree begins to bear fruit at 6 to 8 months of
months of age [18]. Commercially, it is grown in different countries such as Africa, Mex-
age [18]. Commercially, it is grown in different countries such as Africa, Mexico, Hawaii,
ico, Hawaii, and South America, but due to different soil conditions, the nutrient content
and South America, but due to different soil conditions, the nutrient content varies from
varies from
country country[3].
to country to country [3].
3. ArcGIS 10.1-based spatial distribution map of Moringa oleifera, the purple color shows
Figure 3.
the indigenous
the indigenous countries
countries like India, Saudi
like India, Saudi Arabia,
Arabia, and
and East
East indies,
indies, whereas
whereas the
the green
green color
color shows
shows
the introduced countries and regions such as Tropical Asia, Latin America, Africa, Pacific Island,
the introduced countries and regions such as Tropical Asia, Latin America, Africa, Pacific Island,
Caribbean Florida, Madagascar, Central America, Cuba, Philippines, Ethiopia, and Nigeria. GIS lay-
Caribbean Florida, Madagascar, Central America, Cuba, Philippines, Ethiopia, and Nigeria. GIS
ers were obtained from DIVA-GIS, an open-source web platform.
layers were obtained from DIVA-GIS, an open-source web platform.
Int. J. Mol. Sci. 2023, 24, 2098 5 of 36
7. Ethnomedicinal/Traditional Properties
People worldwide have included M. oleifera in their diet since ancient times because
of its vital therapeutic values (Table 1). Various medicines made from the plant are said
to have ethnomedicinal properties for curing diseases and have been used for centuries.
Approximately every part (leaf, pod, bark, gum, flower, seed, seed oil, and root) of this
plant has been used to treat one disease or another [20]. Uses of M. oleifera are observed in
pathological alterations such as antihypertensive [10], anti-anxiety [21], anti-diarrheal [22],
and as a diuretic [23]. Moringa is also used to treat dysentery [24] and colitis [25]. A poultice
made from Moringa leaves is a quick remedy for inflammatory conditions such as glandular
inflammation, headache, and bronchitis [9]. The pods treat hepatitis and relieve joint
pain [19]. The roots are conventionally used to treat kidney stones [26], liver diseases [27],
inflammation [28], ulcers [29], and pain associated with the ear and tooth [30]. The bark of
the stem is used to treat wounds and skin infections [31]. Indians use the gum extracted
from this plant to treat fever, and it is also used to induce abortions [32]. The seeds of
the plant act as a laxative and are used in the treatment of tumors, prostate, and bladder
problems [33]. The seeds show promise for the treatment of arthritis by altering oxidative
stress and reducing inflammation [34]. Preparations from the plant leaves benefit nursing
mothers and malnourished infants and improve the general health of the population. The
leaves have been useful for patients suffering from insomnia [35] and treating wounds [36].
Moringa is used incredibly extensively in the cosmetic industry nowadays, and in ancient
Egyptian history, it was similarly used for preparing dermal ointments [37].
Table 1. Uses of Moringa oleifera listed in Ayurvedic medicinal textbook.
Name of Ayurvedic Text Form of Plant Used Treatment References

Used for treatment of
worms and headache,
Ascites, edema
Charaka Samhita Powder
Hiccough and asthma, [38]
(1000 BC- 4th Cent. AD) Decoction
deafness, tinnitus in the
ear, worm’s
manifestation.
Ashtanga Hridaya Ear ache, deafness, and
Oil [39]
(7th Cent. AD) tinnitus in the ear
Puerperal disorder,
Kashyapa Samhita Decoction
sleeplessness [40]
(6–7th Cent AD) Oil
Edema
Sharangadhara Samhita
Decoction Conjunctivitis [41]
(13 Cent. AD)
Enlargement of spleen,
Yogaratnakara
Decoction worm edema, Ascites, [42]
(17th Cent. A.D.)
fever, abscess.
8. Pharmacological Uses
Recent pharmacological studies have revealed that different extracts of M. oleifera
exhibit different pharmacological activities, such as antimicrobial [43], antifungal [44],
anti-inflammatory [45], antioxidant [46], anticancer [47], fertility [48], wound healing [43],
and other pharmacological activities mentioned below (Table 2).
Plant part Compound Class Structure Therapeutic Activity References
Int. J. Mol. Sci. 2023, 24, 2098 Table 2. Phytoconstituents of Moringa and their relevant therapeutic effects. 6 of 36

Table 2. Phytoconstituents of Moringa and their relevant therapeutic effects.
Rutin Found to have maximum affinity and
Leaves
Plant Part Compound Flavonoid
Class Structure Therapeutic Activity [49,50]
References
(555.6 µ g/g) interaction towards BRAC-1 gene.
Plant part Rutin

Compound
Rutin Class Structure FoundFound
toTherapeutic
have maximum
to have affinity
Activity
maximum and
affinity and References
Leaves
Leaves Flavonoid
Flavonoid [49,50]
[49,50]
(555.6µµg/g)
(555.6 g/g) interaction
interaction towards
towards BRAC-1
BRAC-1 gene.
gene.
Kaempferol
Int. J. Mol. Sci. 2023, 24, x FOR PEER REVIEW
Kaempferol 7 of 40
Leaves
Leaves Flavonoid
Flavonoid Oxidative damage
Oxidative protective
damage activity.
protective activity. [51] [51]
(197.6µµg/g)
(197.6 g/g)

Kaempferol
Leaves Flavonoid Oxidative damage protective activity. [51]
(197.6 µ g/g)
Quercetin Exerts anan
excellent
Leaves Flavonoid Exerts excellenteffect
effect as anti-diabeticagent.
as anti-diabetic [52]
(2030.9 µmol/100 g) agent.
Quercetin
Leaves Flavonoid [52]
(2030.9 µ mol/100 g)
Exerts an excellent effect as anti-diabetic

agent.
Quercetin
Leaves OOcoumaric
coumaricacid
acid Flavonoid [52]
Leaves
Leaves (2030.9 µ mol/100 g) Phenolic acid
Phenolic acid Antioxidant and and
Antioxidant anti-microbial
anti-microbial [53,54]
[53,54]
(0.536
(0.536mg/g)
mg/g)
O coumaric acid
Int. J. Mol. Sci. 2023, 24, 2098 7 of 36

Table 2. Cont.
Plant Part Myricetin

Compound Class Structure Potential prevention of diabetes
Therapeutic mellitus and
Activity References
Leaves Flavonoid [54]
(5.804 mg/g) other diabetic complications
Myricetin
Myricetin Potential prevention
Potential of diabetes
prevention mellitus
of diabetes and
mellitus and
Leaves
Leaves Flavonoid
Flavonoid [54] [54]
(5.804mg/g)
(5.804 mg/g) otherother diabetic
diabetic complications
complications

Ellagic
Ellagicacid
acid Prevents viral viral
Prevents and and
bacterial infections,
bacterial infections,
Leaves
Leaves Polyphenol
Polyphenol [54,55]
[54,55]
(0.078toto0.128
(0.078 0.128 mg/g) potential
potential antioxidant
antioxidant
Ellagic acid Prevents viral and bacterial infections,

Leaves Polyphenol [54,55]
(0.078 to 0.128 mg/g) potential antioxidant
Promising results as anticancer, antioxidant,
Ferulic acid
Leaves Phenol antithrombotic, anti-arrhythmic, and [54,56]
(0.078 to 0.128 mg/g) Promising results as anticancer, antioxidant,
Ferulic acid anti-inflammatory.
Leaves Phenol antithrombotic, anti-arrhythmic, and [54,56]
(0.078 to 0.128 mg/g)
anti-inflammatory.
Boosts athletic performance, reduces fatigue,

Caffeic acid
Leaves Phenol helps weight loss, protects against herpes, [54,57]
(0.409 mg/g)
HIV, cancer.
anti-inflammatory.
Int. J. Mol. Sci. 2023, 24, 2098 8 of 36
Table 2. Cont.
Int. J. Mol. Plant

Sci. 2023,
Part24, x FOR PEERCompound
REVIEW Class Structure Therapeutic Activity 10 of 40
References
Plant part Compound

Class Structure Therapeutic Activity References
10 of 40
BoostsBoosts
athletic performance,
athletic reduces
performance, fatigue,
reduces fatigue,
Caffeic
Caffeicacid
acid
Leaves
Leaves Phenol
Phenol helps weight
helps weightloss, protects
loss, protectsagainst
against herpes,
herpes, HIV, [54,57]
[54,57]
Plant part Compound
(0.409mg/g)
(0.409 mg/g) Class Structure Therapeuticcancer.
Activity References
HIV, cancer.
Sinapic acid Cardioprotective, renoprotective, anxiolytic,
Leaves Phenol [54,58]
(trace amount) neuroprotective.
Sinapic acid Cardioprotective, renoprotective, anxiolytic,
Sinapic
Sinapicacid
acid Cardioprotective, renoprotective,
Cardioprotective, anxiolytic,
renoprotective, anxiolytic,
Leaves
Leaves Phenol
Phenol [54,58]
[54,58]
(traceamount)
neuroprotective.
Gallic acid Anti-inflammatory, anti-neoplastic,

(1.034 mg/g) anti-oxidant
Gallic
Gallicacid
acid Anti-inflammatory, anti-neoplastic,
Anti-inflammatory, anti-neoplastic,
Leaves
Leaves Phenol
Phenol [54,59]
[54,59]
(1.034mg/g)
anti-oxidant
Gallic acid Anti-inflammatory, anti-neoplastic,
Syringic
Syringicacid
acid
Leaves
Leaves Phenol
Phenol Anti-oxidant, antimicrobial.
Anti-oxidant, antimicrobial. [54,60]
[54,60]
(trace amount)
(trace amount)
Syringic acid
Leaves Phenol Anti-oxidant, antimicrobial. [54,60]
(trace amount)
Syringic acid
Leaves Phenol Anti-oxidant, antimicrobial. [54,60]
(trace amount)

Int. J. Mol. Sci. 2023, 24, 2098 9 of 36
Table 2. Cont.
Plant Part Compound Class Structure Therapeutic Activity References

Isorhamnetin
Leaves Flavonoid Anti-oxidant [54,61]
(0.118 mg/g)
Isorhamnetin
(0.118 mg/g)
Isorhamnetin
(0.118 mg/g)

Myricetin
Myricetin Potential prevention
Potential of diabetes
prevention mellitus
of diabetes and
mellitus and 12 of 40
Seeds
Seeds
Plant part Compound
(5.804mg/g)
mg/g)
Flavonoid
Flavonoid
Class Structure Therapeutic
other Activity
diabetic complications
[54] [54]
References
(5.804 other diabetic complications
Myricetin Potential prevention of diabetes mellitus and
Seeds Flavonoid [54]
(5.804 mg/g) other diabetic complications
Anti-inflammatory, pain relieving,

Seeds Glucomoringin Glucosinolates [62]
anti-oxidant, antihypertensive.
Seeds
Seeds β-sitosterol
β-sitosterol Phytosterol
Phytosterol Anti-inflammatory
Anti-inflammatory [63] [63]
Seeds β-sitosterol Phytosterol Anti-inflammatory [63]
Seeds Arachidic acid Fatty acid Increased breast milk production [64]
Seeds β-sitosterol
Int. J. Mol. Sci. 2023, 24, 2098
Phytosterol Anti-inflammatory [63] 10 of 36

Table 2. Cont.
Int. J. Mol.
PlantSci. part
2023, 24, x FOR PEER REVIEW
Compound Class Structure Therapeutic Activity 13 of 40
References
Reduces blood pressure and reduces free
Seeds Oleic acid (70% w/w) Fatty acid [65]
radical damage to the cell.
Reduces blood pressure and reduces free
Plant
Int. J. Mol. Sci.part
Seeds Oleic
2023, 24, x FOR Compound
acid
PEER (70% w/w)
REVIEW Class
Fatty acid Structure Therapeutic Activity References
[65] 13 of 40
radical damage to the cell.
Seeds
Seeds Arachidic
Arachidicacid
acid Fatty acid
Fatty acid Increased breast
Increased milkmilk
breast production
production [64] [64]
Reduces blood
Anxiolytic pressure
effect, usedand reduces free
in membrane
Seeds
Plant part Oleic acid (70%
Myristic
Compound acidw/w) Fatty acid
Class Structure Therapeutic Activity [65]
[66]
References
radical damage
localization toenzyme.
of the the cell.
Anxiolytic effect, used in membrane
Seeds Myristic acid Fatty acid [66]
localization
Reduces bloodblood
Reduces of
pressuretheand
enzyme.
pressure reduces
and free
reduces free
Seeds
Seeds Oleic
Oleicacid
acid(70%
(70% w/w)
w/w) Fattyacid
Fatty acid [65] [65]
radical
radical damage
damage to the
to the cell.cell.
Seeds Palmitic Anxiolytic effect,
Anxiolytic used
andeffect, in membrane
used in membrane
Seeds
Seeds Myristicacid
Myristic acid
acid Fatty
Fatty acid
acid
Fatty acid Trypanocidal anti-leukemic effect [67]
[66] [66]
localization
localization of enzyme.
of the the enzyme.
Seeds
Seeds Palmitic
Palmiticacid
acid Fattyacid
Fatty acid Trypanocidal and and
Trypanocidal anti-leukemic effect
anti-leukemic effect [67] [67]
Anxiolytic effect, used in membrane
Seeds Myristic acid Fatty acid [66]
localization of the enzyme.
Seeds Palmitic acid Fatty acid Trypanocidal and anti-leukemic effect [67]
Seeds
Seeds Procyaniadin
Procyaniadin Flavonoid
Flavonoid Cardioprotective
Cardioprotective [68] [68]
Seeds
Plant part Procyaniadin
Compound Flavonoid
Class Structure Cardioprotective
Therapeutic Activity [68]
References
Seeds Palmitic acid Fatty acid Trypanocidal and anti-leukemic effect [67]
Seeds Procyaniadin Flavonoid Cardioprotective [68]

Treatment of deficiency caused by genetic
Flower D-mannose Carbohydrate [69]
defects, and acute urinary tract infections.
Seeds Procyaniadin Flavonoid defects, and acute urinary tract infections.
Cardioprotective [68]

Anti-oxidant, cardiovascular,
Stem β-sitosterol Phytosterol [63]
immunomodulatory
Int. J. Mol. Sci. 2023, 24, 2098 11 of 36
Table 2. Cont.
Anti-oxidant, cardiovascular,
Stem β-sitosterol Phytosterol Anti-oxidant, cardiovascular, [63]
Stem β-sitosterol Phytosterol immunomodulatory [63]
immunomodulatory
Int. J. Mol. Sci. 2023, 24, 2098 12 of 36
8.1. Antimicrobial and Antifungal Activity

M. oleifera ethanolic root extract contains a compound N-benzylethyl thioformate
(an aglycone of deoxyniazimincin) responsible for the antimicrobial and antifungal effect
toward an extensive array of microbes and fungi [44]. M. oleifera methanolic leaf extract may
exert inhibition of urinary tract infections caused by Gram-negative and Gram-positive bac-
teria such as Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, and Staphylococcus
saprophyticus [69].
The inhibitory effect of extracts from leaves, seeds, and stems of M. oleifera has been
specified in various fungal strains such as Aspergillus flavus, Aspergillus terreus, As-
pergillus nidulans, Rhizoctonia solani, Aspergillus niger, Aspergillus oryzae, Fusarium
solani, Penicillium sclerotigenum, Cladosporium cladosporioides, Trichophyton men-
tagrophytes, Penicillium species, Pullarium species [44]. M. oleifera seeds have active
components 4-(alpha-L-rhamanosyloxy) benzyl isothiocyanates, which are believed to be
responsible for their antimicrobial activity [70]. The juice of Moringa leaves also showed
potential against human pathogenic bacteria [43]. The methanolic leaf extract has nearly
99% inhibition against Botrytis cinerea (a necrotrophic plant fungus) [71].
The fruit of M. oleifera contains alkaloids, flavonoids, and steroids, which have an
inhibitory effect against the culture of Candida albicans by either denaturing the protein or
inhibiting the germination of spores through the steroid ring they contain [72].
Strong inhibitory effects of moringa seed kernel extract were observed for Bacillus
cereus, Staphylococcus aureus, Mucor species, and Aspergillus species. However, it was less effec-
tive against P. aeruginosa and E. coli. This indicated that, except for E. coli and P. aeruginosa,
moringa seed kernel extract might be utilized to treat infections caused by these species [73].
A recent study has been conducted, which states that only apolar extract obtained from
seeds of M. oleifera showed anti-microbial activity against Gram-positive bacteria [74].
8.2. Anti-Inflammatory Activity

A significant anti-inflammatory effect was observed in different parts of M. oleifera (leaf,
pods, flowers, and roots). It was observed that the isolated compound (4-[2-o-Acetyl-alpha
-l-rahamnoslyloxy) benzyl] thiocynate from Moringa possessed nitric oxide inhibitory activ-
ity and was subsequently found to be effective in Raw264.7 cell lines [75]. A compound de-
rived from M. oleifera roots, known as aurnatiamide acetate and 1,3-dibenzylurea, inhibited
TNF-α production [76]. Active compounds such as tannins, phenols, alkaloids, flavanoids,
carotenoids β-sitosterol, vanillin, and moringin have anti-inflammatory properties [32].
The M. oleifera fruit extract blocked nuclear factor kappa B (NF κB) translocation, and the
chloroform extract was found to be cytotoxic at high concentrations (500–1000 µg/mL) [77].
M. oleifera leaves extract was used in mice for treating atopic dermatitis in human ker-
atinocytes and was found to be effective in reducing the expression of mannose receptor
mRNA, thymic stromal lymphopoietin, and retinoic acid-related orphan receptor γT in ear
tissues (Figure 4) [78].
8.3. Oxidative Stress

The results of M. oleifera were observed in methotrexate-induced mice. The study
aimed to look into a probable palliative effect of M. oleifera extract on mice. The mice re-
ceived the extract one week before administering methotrexate injection, and this treatment
was continued for 12 days. The result showed that pretreatment with an extract of M.
oleifera on mice poisoned with methotrexate could protect them from oxidative stress [79].
The antioxidant activity of ethanolic extract M. oleifera stems exhibited a protective
effect against epidermal oxidative stress injury induced by H2 O2 in keratinocytes. The
result displayed that the stems showed antioxidant potential, and, therefore, can be used as
an excellent and preventive source in animal epidermal oxidative stress injury [80].
The research investigated the antioxidant potential of Moringa leaves against di-
clofenac sodium-induced liver toxicity in animals. The researchers concluded that the
Int. J. Mol. Sci. 2023, 24, 2098 13 of 36

extract was significantly effective against diclofenac-induced liver toxicity and, therefore,
can be considered liver protective [81].
Figure 4. M. oleifera, as an oxidative and inflammatory marker, inhibits IKBα phosphorylation,

Figure thereby
4. M. oleifera, as anNFKB
preventing oxidative andfactor
(nuclear inflammatory
kappa B) marker, inhibits
inhibition. IKBα the
It prevents phosphorylation,
nuclear translocation
thereby preventing NFKB (nuclear factor kappa B) inhibition. It prevents the nuclear translocation
and dimerization of IkBα and NFKB, thereby inhibiting the formation of inflammatory proteins such
and dimerization of IkBα and NFKB, thereby inhibiting the formation of inflammatory proteins
as TNFα(tumor necrosis factor), COX-2(cyclooxygenase-2), IL6(interleukin -6), and iNos(inducible
such as TNFα(tumor necrosis factor), COX-2(cyclooxygenase-2), IL6(interleukin -6), and iNos(in-
duciblenitric
nitricoxide synthase)
oxide synthase)and
andthereby reducing
thereby the the
reducing inflammation and and
inflammation curing otherother
curing disorders like obesity,
disorders
arthritis,
like obesity, cancer,cancer,
arthritis, diabetes, and ulcer.
diabetes, and ulcer.
8.4. Anti-Oxidant
8.3. Oxidative Stress Activity
Bioactive
The results of M.compounds such observed
oleifera were as glycosylates [82], isothiocyanates [62],
in methotrexate-induced mice.thiocarbamates
The study [83],
flavonoids [84], and certain other compounds from Moringa
aimed to look into a probable palliative effect of M. oleifera extract on mice. The mice pods have been investigated
re-
for reactive oxygen spices. The aqueous extract has been shown
ceived the extract one week before administering methotrexate injection, and this treatment to be a potent free radical
scavenger
was continued foragainst
12 days. free
Theradicles [45]. Previous
result showed studies suggest
that pretreatment withthat the antioxidant
an extract potential
of M. oleifera
on mice might be due
poisoned withto methotrexate
kaempferol, couldwhichprotect
is mainly
them found
from in plant leaves
oxidative stress [43].
[79]. The synergistic
outcome
The of Moringa
antioxidant activitywas observed extract
of ethanolic with piperine
M. oleifera andstems
curcumin
exhibitedon oxidative
a protective stress in-
duced by beryllium toxicity in Wistar rats [85]. The alcoholic
effect against epidermal oxidative stress injury induced by H2O2 in keratinocytes. The re- extract of the plant reduced
sult displayed that the stems showed antioxidant potential, and, therefore, can be used as [86].
glucose-induced cataractogenesis in isolated goat eye lenses by controlling GSH levels
Myricetin,
an excellent derived from
and preventive the Moringa
source in animalseed extract,oxidative
epidermal has proved to injury
stress be a better
[80]. antioxidant
than BHT (butylated hydroxytoluene) and alpha-tocopherol.
The research investigated the antioxidant potential of Moringa leaves against M. oleifera leaf diclo-
extract and
compounds, such as isoquercetin, astragalin, and crypto-chlorogenic
fenac sodium-induced liver toxicity in animals. The researchers concluded that the extract acid, help lower ROS
in HEK-293effective
was significantly cells [87]. Moringa
against is also helpful inliver
diclofenac-induced reducing plasma
toxicity and, monoaldehyde
therefore, can be(MDA)
levels in fasting plasma
considered liver protective [81]. glucose (FPG) concentration in healthy volunteers compared to the
individuals fed with warm water. A dose-dependent upsurge in GSH and reduced MDA
levels wereActivity
8.4. Anti-Oxidant observed with alcoholic extract of the plant without toxic effect till 100 mg/kg
(Figure 4) [46].
Bioactive compounds such as glycosylates [82], isothiocyanates [62], thiocarbamates
[83], flavonoids [84], and
8.5. Anti-Cancer certain other compounds from Moringa pods have been investi-
Activity
gated for reactive
Several parts ofspices.
oxygen moringaThe(fruits,
aqueous extract
leaves, has been
flowers, shown
stems) havetobeenbe ashown
potentto free
be bene-
radicalficial
scavenger
againstagainst
cancer,free radicles
a deadly [45]. Previous
disease. The isolatedstudies suggest that
compounds the antioxidant
thiocarbamate and isoth-
potential might be
iocyanate fromduemoringa
to kaempferol, which is of
act as inhibitors mainly
tumor found
cells in plant leaves
[15,47]. [43]. The
The dichloromethane
synergistic outcome of Moringa was observed with piperine and curcumin
fraction was found to be cytotoxic for MCF7 breast cancer cells [88]. Niazimincin has been on oxidative
stress projected
induced by as beryllium
an effectivetoxicity in Wistar rats
chemopreventive [85].
agent in The alcoholic
chemical extract of the
carcinogenesis plant
[44]. Alcoholic
reduced glucose-induced cataractogenesis in isolated goat eye lenses by controlling GSH
levels [86]. Myricetin, derived from the Moringa seed extract, has proved to be a better
antioxidant than BHT (butylated hydroxytoluene) and alpha-tocopherol. M. oleifera leaf
Int. J. Mol. Sci. 2023, 24, 2098 14 of 36
and hydro-methanolic extracts of fruits and leaves have shown significant tumor growth
retardation in the melanoma mouse model [32]. Soluble cold distilled water from Moringa
inhibited tumor cell growth and reduced ROS (reactive oxygen species) in cancer cells [45].
A recent study based on computational modelling suggests that M. oleifera contains rutin
with the highest binding affinity with BRAC-1 (Breast Cancer Gene-1) [49].
8.6. Fertility and Anti-Fertility Activity

Adding to the list of beneficial effects of Moringa, the various parts of the plant possess
fertility and abortion-inducing properties. The aqueous extract at a 200 and 400 mg/kg
dose has been found to be more abortifacient and anti-fertility effects [44]. Recent studies
on hot and cold extracts of leaves of M. oleifera propose that ingestion of Moringa before,
after, and during pregnancy may lead to adverse fetal developmental outcomes by causing
rigorous contraction of the uterine wall [89].
8.7. Hepatoprotective Activity

Among the numerous flavonoids (quercetin, kaempferol, isoquercetin, rhamnetin,
etc.,) present in Moringa, quercetin in Moringa flowers is thought to be accountable for the
hepatoprotective effect [44]. Methanolic extract at low dose showed changes in hepato-renal
and hematological profile with significant changes in serum aminotransferase concentration,
plasma cholesterol level, alkaline phosphate, bilirubin, and serum LPO levels. However, the
higher dose of the extract altered total bilirubin, blood urea nitrogen, and non-protein nitro-
gen levels and decreased the clotting time [43]. Liver injuries induced by acetaminophen
in Sprague-Dawley rats, where the standard drug taken was silymarin, Moringa showed
similar hepatoprotective properties in these rats by dropping the levels of AST, ALT, and
ALP [90]. The seeds were also found to be effective against carbon tetrachloride-induced
liver fibrosis, as evidenced by a reduction in serum aminotransferase activity and globulin
levels [91]. Treatment with this plant extract for about 21 days regularly as diet significantly
reduced liver injury, and this effect was found due to alkaloid, quercetin, kaempferol,
flavonoids, ascorbic acid, and benzyl glucosinolates in this plant [32].
8.8. Cardiovascular Activity

The freeze-dried aqueous and alcoholic extract of M. oleifera showed cardioprotective
activity in animals induced with myocardial infarction by isoproterenol [92]. Chronic treat-
ment of M. oleifera was effective on isoproterenol-induced hemodynamics and improved
the levels of enzymes such as SOD, catalase, lactase dehydrogenase, glutathione peroxi-
dase, and creatine kinase [92]. Butanolic extract has been proven to be a rich antioxidant
source in rats with cardiac necrosis induced with isoproterenol. Moreover, it was found
to significantly reduce inflammatory levels and myocardial necrosis due to the presence
of the compound N-α-rhamnopyranosyl vincosamide [93]. Moringa leaves significantly
lowered cholesterol levels by showing a protective effect on hypertensive rats. The active
constituents believed to be responsible for this activity were identified as niazirmin A,
niazirimin B, and niazimincin [32].
8.9. Anti-Ulcer/Gastroprotective Activity

Bisphenols and flavonoids found in moringa leaves showed a reduced level of ulcer
index, duodenal ulcer, and stress ulcer in the ibuprofen-induced gastric ulcer model [32].
Moringa extract was shown to significantly reduce free radicals and neutralize the acidic
behavior of gastric juice and have a protective effect on the development of gastric ulcer [94].
The presence of flavonoids in the plant has been shown to have a protective effect on ulcer
formation by increasing capillary resistance and improving microcirculation, resulting in
less cell injury [95].
Int. J. Mol. Sci. 2023, 24, 2098 15 of 36
8.10. Analgesic/Antipyretic Activity

Moringa leaf extract shows analgesic activity in almost all tree parts in central and
peripheral animal models [32]. Multiple factions of alcoholic extracts such as petroleum
ether, n-butanol, ethyl acetate, and dimethyl ether were found to have potent analgesic
activity compared to standard aspirin [96]. At a dosage of 30–300 mg/kg, the polar and
non-polar extract of leaves showed a remarkable drop in prostaglandin and bradykinin
levels compared to the seed and root extract in a nociceptive study of formalin-induced paw
edema [96]. The ether and ethyl acetate fractions of the seeds were studied in a hyperpyrexia
model [97], keeping paracetamol as standard 200 mg/kg, and the extract proved to have
the best antipyretic activity among all [45].
8.11. Neuropharmacological Activity

Previous results have proved that leaves extract reestablishes levels of monoamine
in the brain and is very helpful in Alzheimer’s disease, while the in vitro activity of
the ethanolic extract of the leaves showed an anticonvulsant effect on dopamine and
norepinephrine levels, locomotor activity, and serotonin (5HT) in the brain in penicillin-
induced convulsions [98,99]. The methanolic root extract in mice induced by pentobarbital
sodium and diazepam has remarkable sedative effects on the CNS by improving sleep
duration [35]. The toluene acetate fraction of the methanolic extract proved its potency as
a possible nootropic agent [97]. The leaves have shown good anticonvulsant activity in
a phenyl tetrazoline and maximal electric shock-induced model using male albino mice [98].
The aqueous extract of the roots blocked the epileptic seizures induced by penicillin in adult
albino rats [99]. The ethanolic leaves extract exhibited anxiolytic properties, which
Int. J. Mol. Sci. 2023, 24, x FOR PEER REVIEW 16 ofwere
38
confirmed in behavioral experiments using the actophotometer and the rotarod device,
respectively (Figure 5) [32].
Figure 5. The various phytoconstituents present in M oleifera are responsible for numerous neuro-
Figure 5. The various phytoconstituents present in M oleifera are responsible for numerous neuro-
protective effects. M. oleifera is responsible for upregulating synaptic activity, cholinergic activity,
protective effects. M. oleifera is responsible for upregulating synaptic activity, cholinergic activity,
dopaminergic activity, signaling of NrF2 (Nuclear factor erythroid 2-related factor 2), and simultane-
dopaminergic activity, signaling of NrF2 (Nuclear factor erythroid 2-related factor 2), and simulta-
ously decreasing
neously decreasing beta-amyloid
beta-amyloid toxicity
toxicity and
and phosphorylation
phosphorylation of
of tau
tau proteins.
proteins.
8.12.
8.12. Neuropathic
Neuropathic Pain
Pain
The broad spectrum of of
The broad spectrum phytoconstituents
phytoconstituents of of
thethe leaves
leaves extract
extract of of Moringa
Moringa has
has ledled
researchers
researchers to to develop
develop a herbal
a herbal alternative
alternative forfor treating
treating chronic
chronic neuropathic
neuropathic pain
pain caused
caused
byby constriction.
constriction. The
The need
need to to limit
limit conventional
conventional analgesics
analgesics forfor this
this disease.
disease. Diabetic
Diabetic rats
rats
inflicted with neuropathic pain caused by chronic constriction were used for the study.
Tests conducted before and after treatment with moringa leaves showed that they signif-
icantly altered the neuropathic pain condition in diabetic rats. It suggests that the drop in
oxidative stress might be the underlying mechanism in treating neuropathic pain and thus
Int. J. Mol. Sci. 2023, 24, 2098 16 of 36
inflicted with neuropathic pain caused by chronic constriction were used for the study. Tests
conducted before and after treatment with moringa leaves showed that they significantly
altered the neuropathic pain condition in diabetic rats. It suggests that the drop in oxidative
stress might be the underlying mechanism in treating neuropathic pain and thus could be
used as an effective novel source for the same [100].
A research team explored the bio-guided fractions of Moringa seed extract on a diabetes-
induced neuropathic pain model. After conducting various oxidative and other experi-
mental studies on induced and treated rats, the team concluded that the extract-treated
rats exhibited reasonable glycemic control and antinociceptive properties and proved to be
a powerful neuroprotective agent with a high margin of safety (Figure 5) [101].
8.13. Wound Healing Effect

A significant effect in studies on wound healing after incision or excision was demon-
strated for ethyl acetate, and water extract of M. oleifera leaves at a 300 mg/kg dose [43].
Studies reported that in preclinical studies, leaves, seeds, and dried pulp extracts have
shown effective enhancement of wound closure, granuloma rupture strength, and reduc-
tion of skin rupture strength in the scar area [102]. Leaf extracts have shown promising
results in diabetic animals by improving the downregulation of inflammatory markers
and increasing the vascular endothelial growth factor level in the injured tissue [32]. Com-
pounds present in aqueous extract have shown a considerable effect on diabetic foot ulcers
by downregulating the levels of various inflammatory markers [102]. The researcher con-
ducted an in vitro assay to select the standardized extract with the highest potency, which
was then converted into a film for wound healing. The result showed that the aqueous
extract had the maximum cell proliferation and migration properties among the different
extracts [103].
8.14. Immunomodulatory Activity

Methanolic extract of the plant contains active constituents such as isothiocyanate
and glycoside cyanide, which exhibit immunostimulatory activity and effectively enhance
immunity. The recent review paper suggests that various bioactive compounds have been
used to treat various immune-related disorders such as cancer, hypertension, and diabetes,
thereby enhancing host immunity [104].
8.15. Hematological Activity

M. oleifera has demonstrated its significant benefits in hematological activities. A ran-
domized, double-blind study suggests that aqueous leaf extract effectively improves
women’s low hemoglobin levels (8–12 g/dL) [105]. Another study showed that M. oleifera
leaves, when taken for 14 days by healthy volunteers, significantly improved platelet
counts [32].
8.16. Anti-Obesity Activity

In a study, oral treatment with leaf powder of M. oleifera for a duration of nearly
49 days was found to significantly reduce body mass index (BMI) in rats suffering from
hypercholesterolemia [106]. The mechanistic approach behind this was the downregulation
of mRNA expression of the hormones resistin and leptin and the concomitant increase in
regulation of the gene adiponectin in rats [32]. A recent study revealed the mechanistic
approach for the anti-obesity effect of M. oleifera. The plant significantly improved lipid
profile by reducing body weight. It also regulated adipogenesis-related genes, increased
glucose tolerance, and decreased levels of hormones such as vaspin, leptin, and resistin
(Figure 6) [107].
of mRNA expression of the hormones resistin and leptin and the concomitant increase in
regulation of the gene adiponectin in rats [32]. A recent study revealed the mechanistic
approach for the anti-obesity effect of M. oleifera. The plant significantly improved lipid
profile by reducing body weight. It also regulated adipogenesis-related genes, increased
glucose tolerance, and decreased levels of hormones such as vaspin, leptin, and resistin
Int. J. Mol. Sci. 2023, 24, 2098 17 of 36
(Figure 6) [107].
Figure 6. M. oleifera as a promising anti-obesity agent. Various in-vitro findings suggest that sup-
plements of M.asoleifera
Figure 6. M. oleifera cause direct
a promising inhibition
anti-obesity of pancreatic
agent. lipase,findings
Various in-vitro thus reducing
suggestthe thatconversion
supple- of
triglycerides into simple. Moringa has fat storage regulation by upregulation of lipolysis-associated
ments of M. oleifera cause direct inhibition of pancreatic lipase, thus reducing the conversion of tri-
proteininto
glycerides andsimple.
down-regulating
Moringa has thefat
expression of protein related
storage regulation to fat storage.
by upregulation It is also effective in the
of lipolysis-associated
protein and down-regulating
improvement the levels.
of antioxidant expression of protein
Besides related to
these, Moringa fat storage.
is also It is for
responsible alsoincreasing
effective ghrelin
in
the improvement of antioxidant
levels and decreasing leptin, levels.
producingBesides these,ofMoringa
a feeling satiety. is also responsible for increasing
ghrelin levels and decreasing leptin, producing a feeling of satiety.
8.17. Anti-Allergic Activity
8.17. Anti-Allergic Activity
The ethanolic seeds extract reduced histamine release and also suppressed the anaphy-
laxis ethanolic
The induced byseeds extract reduced histamine
anti-immunoglobulin release and
G. The mechanism also suppressed
underlying the
this effect ana-
may be the
phylaxis induced by anti-immunoglobulin G. The mechanism underlying this effect
membrane-stabilizing potential of mast cells in an oval albumin sensitization modelmay be[32].
the membrane-stabilizing potential of mast cells in an oval albumin sensitization model [32].
8.18. Anti-Diabetic Activity
Moringa leaves showed excellent results in the glucose tolerance of Wistar and Goto-
Kakizaki rats and also lowered blood glucose levels. The aqueous extract showed an antidi-
abetic effect in rats by controlling blood glucose levels, protein, sugar, and hemoglobin [45].
The leaves of the plant were found to lower glucose levels within three hours of intake,
but not more than the standard drug glibenclamide. Moringa seeds, when administered
orally, contain insulin-like proteins that have antigenic epitopes such as insulin and exhibit
antihyperglycemic activity [108]. Leaf extracts of the plant also have antidiabetic activity
as they increased CAT and MDA levels, reduced FPG levels, hemoglobin levels, LDL-C,
and VLDL-C in type 2 diabetic patients and, most importantly, increased insulin levels
in healthy subjects [109]. The seed extract of the plant reduced LPO levels and amplified
the antioxidant effect in mice induced with streptozotocin, the seed extract was also able
to reduce IgG, IgA, and IL -6 parameters and pancreatic β-cell activity, and it was sug-
gested that the bioactive compound responsible for this effect were quercetin, kaempferol,
glucomoringin, chlorogenic acid, and isothiocyanates [110].
8.19. Diuretic Activity

The alcoholic and aqueous root extract of M. oleifera significantly affects calcium oxalate
urolithiasis in male rats. This reduction was observed due to the decrease in the retention
level of oxalates, calcium and phosphates as well as serum urea nitrogen, creatinine, and
uric acid [23].
8.20. Angiotensin Converting Enzyme (ACE) Activity

Compounds such as niazimin-A, niazicin-A, and niaziminin-B are stated to be present
in the M. oleifera plant extract. These compounds were found to have potent antihyper-
tensive activity when targeted to (ACE), an important enzyme of the renin-angiotensin
Int. J. Mol. Sci. 2023, 24, 2098 18 of 36
system. The researchers observed this activity by protein–ligand docking and found that
the compounds have a high affinity for the angiotensin-converting enzyme compared
with captopril and enalapril (standard drug) [111]. The angiotensin enzyme rennin plays
a prominent role in regulating blood pressure and leading to diseases such as hyperten-
sion, kidney disease, and other cardiovascular diseases. The study found that the role
of M. oleifera with two other plants (Azadirachta indica and Hibiscus sabdariffa) inhibited
the enzyme with percentage inhibition (71.8%, 74%, and 73.4%) compared to standard
drugs (captopril and enalapril). The compound responsible for this activity of Moringa
was termed β-sitosterol [112].
8.21. Anti-Venom Effect

The leaves of the plant extract have been shown to be effective against the venom of
Naja Nigricollis (a snake species) in rats. This snake’s venom contains potent neurotoxins
that cause the degradation of phospholipids at the plasma membrane, affecting the normal
neurotransmission process and causing hemolysis and hemorrhage. The results showed
that Moringa extract effectively cured acute anemia, and a remarkable increase in micronu-
cleated polychromatic erythrocytes was observed in rats treated with M. oleifera [113].
8.22. Cytotoxicity Effect

The cytotoxic potential of M. oleifera on human mesenchymal myeloma cell lines is
observed in methanolic extract. The results of the extracts showed a higher ID50 value than
other extracts. The researchers also found that the alkaloids and flavonoids contained in
the plant showed some similarity to vincristine and vinblastine by random experiments.
Therefore, the plant can be recommended for the herbal treatment of myeloma patients [47].
It was found that the ethanolic leaves extract of M. oleifera contains active constituents
that can alleviate cyclophosphamide-induced testicular toxicity by promoting genes associ-
ated with the functional integrity of spermatozoa and enlargement of DNA in spermatogo-
nia. Therefore, the administration of the extract not only improved blood and intestinal
hormone levels but also modulated the expression of genes responsible for Sertoli and
spermatogonial cells [114].
9. Toxicity
Various experimental procedures were conducted to evaluate the toxic potential of the
plant. A random selection of female non-pregnant Wistar albino rats was conducted with
an oral dose of 2000 mg/kg aqueous methanol solution. Blood samples were collected,
and the ALT, AST, and total bilirubin content were determined. The outcome of the study
suggested that the lethal dose of the aqueous extract was higher than 2000 mg/kg in female
rats [53].
A similar study was also conducted in Sprague-Dawley rats to evaluate the acute toxic
potential of Moringa leaf powder. The experiment also found that oral administration of
dried leaves up to 2000 mg/kg had no harmful or lethal effect on the human body [115].
The toxicity of M. oleifera seeds in rats was observed at acute and subacute levels
(methanolic extract). Acute toxicity was seen at a dose of 4000 mg/kg, whereas mortality
was observed at a dose of 5000 mg/kg. Therefore, in a nut shell, it could be summarized
that the seed extract could be safe for nutritional use [116].
Experiments conducted for acute and subacute studies indicated that the stem bark ex-
tract did not cause any toxic effect in the acute and subacute toxic studies up to 2000 mg/kg.
Therefore, the researchers concluded that the stem bark of M. oleifera can be considered
non-toxic when administered orally [117].
The subacute toxicity test at a dose of 250, 500, and 1500 mg/kg was performed
for 60 days. The result showed that the lethal dose was 1585 mg/kg without significant
alterations in sperm quality, biochemical, and hematological parameters compared to the
control group [105].
Int. J. Mol. Sci. 2023, 24, 2098 19 of 36
The acute toxic study (5000 mg/kg) and subacute (40–1000 mg/kg) results showed no
adverse reaction during these studies. However, increased ALT, ALP, and lower creatinine
levels were observed. Therefore, it could be concluded that consumption is safe, but intake
should not surpass 70 gm/day to prevent cumulative toxicity [118].
10. Clinical Trials

To date, 25 clinical studies have been conducted on M. oleifera, fifteen of which have
been completed. Nine of these fifteen studies addressed M. oleifera as part of a diet, while
the remaining studies were limited to disease-specific drug interventions. Overall, the
studies demonstrated the efficacy of using moringa for conditions such as malnutrition,
chronic kidney disease, HIV infection, and reproductive health [119].
A clinical study highlighted the significant role of M. oleifera as an anti-asthmatic
agent. In this study, researchers used seed kernels of M. oleifera to treat symptoms of
bronchial asthma. Candidates were selected based on inclusion and exclusion criteria, with
respiratory parameters and blood samples recorded before and at the end of three weeks of
treatment with M. oleifera. The extract was administered to patients in the form of dried
powder at a dose of 3 g twice daily for three weeks, and they were instructed to take water
with the powder. Symptoms were graded as severe, moderate, and mild on a point table.
The results indicate that symptoms and respiratory functions decreased; M. oleifera seeds
can effectively treat bronchial asthma [120].
11. Phytopharmaceutical Formulations

Plant extracts have always attracted researchers’ attention for producing various phar-
maceutical products. This process usually involves the production of medicinal products
characterized by two things: first, the production of a stable product, and second, patient
compliance. The advantage of Moringa plant extracts is that it appears to be exceed-
ingly safe at the doses and in the amounts commonly utilized for therapeutic efficacy [20].
M. oleifera has been widely accepted in the research area, and scientists have used an array
of approaches to develop various formulations. The various phytoformulations prepared
using M. oleifera are tabulated below (Table 3).
Int. J. Mol. Sci. 2023, 24, 2098 20 of 36
Table 3. Phytopharmaceutical formulations prepared using M. oleifera extract.
Method of Preparation and

Plant Part Used Nature of Extract Formulation Application Inference References
Polymers/Excipients Used
Suspending method • The potent anti-ulcer activity was observed in

Leaves Ethyl acetate Polyherbal formulation Anti-ulcer polyherbal formulations. [121]
(carboxy methyl cellulose)
Water in oil mixing • The methanolic extract had a more anti-inflammatory

(wool fat, hard paraffin, cetostearyl alcohol, effect than the aqueous extract.
Leaves Aqueous/methanolic Polyherbal ointments PEG4000, PEG400, sorbitol mono-oleate, Edema • Apart from potent anti-inflammatory activity, the [122]
liquid paraffin, white beeswax, span 60, -miscible base ointment showed good drug diffusion.
tween 60)
Vortexing • Showed higher permeation rather than pure oil.

Seed Oil Micro-dispersion Anti-inflammatory • Tween 80 enhances the permeation. [123]
(Span 80, tween 80)
• Flavoring agents gave better acceptance for the

Wet granulation consumer than formulation with no addition of
Leaves Ethanolic Lozenges (Polyvinyl-pyrrolidone, magnesium stearate, Anti-microbial activity flavoring agent. [124]
menthol, vanillin) • Due to limited solubility of quercetin in aq. phase, only
40–50% of quercetin is released.
• Targetability increases when seed oil is formulated in

nano-micelle.
Microemulsion method Mitochondrial cancer cell • Nanomicelles kill 50% colon cancerous Caco-2 cells
Seed Oil Nano-micelle [125]
(Tween 80, Ethanol) apoptosis compared to seed oil which kills only 40% of cancer
cells.
• On increasing PF127 concentration, the viscosity of

Cold method in-situ gel increases.
(poly (ethylene glycol) (PEG400), Pluronic • PF127 exhibited less mucoadhesion as compared to
Leaves + fruits Thermo-reversible
Hydro-alcoholic F127, xanthum gum, carbopol 934), Allergic rhinitis HPMC/carbopol/xanthan gum. [126]
(Embelia ribes) in-situ nasal gel
hydroxypropyl methylcellulose (HPMC • Plant in situ gel was formulated to overcome low
K4M). bioavailability and first-pass metabolism.
• Aq. leaf extracts showed effective results in cell

Solvent casting method proliferation and migration properties.
Leaves Aqueous, ethanolic Film dressing Wound healing • Optimal physicochemical properties were exhibited by [127]
(Alginate, pectin)
the extract.
Wet granulation • The effervescent times of all formulations were less

Leaves Ethanolic Effervescent tablets (70% ethanol, lactose, citric acid, tartaric acid, Anti-anemia than 2 min, and thus all lie within the range mentioned [128]
sodium bicarbonate, aspartame, PEG600) in the pharmacopoeia standard.
Int. J. Mol. Sci. 2023, 24, 2098 21 of 36
Table 3. Cont.

• Optimized formulation showed 60% inhibition,

Triturating process whereas the standard inhibited 65% protein
(Oleic acid, sodium hydroxide, potassium denaturation.
Seed Oil Anti-inflammatory cream Anti-inflammatory [129]
hydroxide, aluminum hydroxide, liquid • Oil reduced paw edema by 64%, whereas formulation
ammonia, sodium benzoate). reduced it by 70%.
• ZOI increases with an increase in the concentration of

AgNPs against Candida albicans.
Shaking method • The agar plate distributed with the highest
Leaves Silver NPs (AgNPs) Anti-fungal activity [130]
(Silver nitrate) concentration of AgNPs exhibited lowest cultural
population.
• Hydrocolloid dressing is free of any irritants or toxic

substances.
Solvent casting method Wound healing in diabetic • 0.5% and 0.1 % film dressing converts to gel after being
Leaves Aqueous Hydrocolloid film dressing [131]
(sodium alginate, pectin) condition exposed to wounds compared to 1% due to rapid
gelation.
Cold technique • Dose-dependent results of the prepared formulation

Leaves Hydro-alcoholic In-situ gel (Pluronic F127, gellan gum, glycerine, Allergic rhinitis were seen in mice induced with ova albumin along with [132]
Carbopol 934) a significant decrease in Ig E levels.
• PEO concentrations and nanofiber diameter were

directly proportional.
• Polymers in low concentration lead to poor
entanglement of chain and produce beads or lumps of
Electrospinning nanofibers and also form discontinuous fibers.
Nanofibers impregnated
Leaves Aqueous (poly-(ethylene oxide) (PEO), sodium Chronic Wound dressing • At very high concentrations, the electrospinning [133]
onto Hydrocolloid film
alginate, pectin, glycerol) stainless needle gets blocked, and polymer ejection gets
obstructed.
• Electrospinning time increases, and the release of
bioactive from film increases.
• Ethanolic extract proved to be a better composite as

compared to aqueous extract.
Sodium hypophosphite, silver nitrate, citric • ZOI is higher with alcoholic extract than the aqueous
Silver nanoparticle loaded
Leaves Aqueous/Ethanolic acid, Kaolin (clay), Chitosan (LMW), sodium Anti-oxidant extract. [134]
Composites
carbonate. • Fabrics with AgNPs composites showed excellent UV
protection than clay composites.
Int. J. Mol. Sci. 2023, 24, 2098 22 of 36
Table 3. Cont.

• Decreasing the extract amount increases the

entrapment efficiency.
Polymeric microparticles Spray dried method • Unloaded MPs have wrinkled surfaces, whereas
Leaves Hydro-alcoholic Exuding wound treatment extract-loaded MPs have spherical and smooth surface. [135]
(MPs) (Chitosan)
• The gel produces a covering layer that protects the
wound because of chitosan.
• Nanoparticles formed showed

concentration-dependent inhibition.
Mixing method • Iron nanorods showed strong inhibition towards
Leaves Aqueous Iron oxide nanorods Anti-bacterial property [136]
(Iron (III) chloride hexahydrate) bacterial strain compared to conventional anti-bacterial
drugs.
Pour molding method • Suppositories containing Moringa seed oil showed

(Macrogol, dika fat, liquid paraffin, effective results against hemorrhoids.
Seed Oil Suppositories Hemorrhoids • The incorporation of seed oil in suppositories reduced [137]
Polyethylene glycol 1000 & 4000, petroleum
ether) their melting point.
Stirring method • Viscosity increases as the concentration of suspending

Hepato-protection against
Leaves Ethanolic Oral suspension (Sodium carboxymethyl cellulose, propylene material increases. [138]
Isoniazid
glycol, benzoate, sorbitol)
Wet granulation method • Tween 20 improved dissolution as compared to extract.

(Gum Arabic, HPMC, Methocel K100M CR, • Granule formation increases the solubility of M. oleifera
Anti-inflammatory and extract, thereby effectively reducing paw thickness.
Leaves Ethanolic Granules magnesium stearate, Avicel PH200, tween 20, [139]
anti-arthritic • Body weight reduced at first six days and later
40, 80, span 20, 40, Poloxamer 407, sodium
lauryl sulphate) increased significantly due to gum arabica.
• Pectin produced CGT with a higher swelling ratio

compared to gelatin.
• Higher pectin and gelatin concentrations strengthened
Heating and Congealing the gel structure, and the dissolution time increased
Chewable gummy tablets (Gelatin, high methoxyl pectin, mannitol, Evaluation of Chewable CGT.
Leaves Powder • Pectin-based CGT’s did not show syneresis, whereas [140]
(CGT) sucrose, propylene glycol, citric acid, corn oil, gummy tablets
sodium benzoate) CGT’s with 5% gelatin experienced syneresis.
• Higher hardness values are due to increased gelatin
concentration.
• Pectin-based CGT had higher gumminess.
Int. J. Mol. Sci. 2023, 24, 2098 23 of 36
Table 3. Cont.

Mixing method • M. oleifera hydrogel showed significant wound-healing

(Carbopol, propylparaben sodium, activity.
Seeds n-hexane Herbal hydrogel Wound healing • Hydrogel positively affects the proliferation of cells, [141]
methylparaben sodium, propylene glycol,
triethanolamine) granular tissue formation, and epithelization.
• A dose less than 2000 mg/kg showed better in vivo

Thin-layer hydration method assessment.
Leaves Aqueous Phytosome Breast cancer [142]
(soy phosphatidylcholine, TrizolTM) • Inhibition of 4T1 cells is dose-dependent.
• After eight weeks of storage, decreased in the pH of

Dissolving method preparation as Moringa leaves experience
Leaves Ethanolic Emulgel Anti-oxidant activity [143]
(Carbopol 940, triethanolamine Tween 80) decomposition of fatty acid.
Int. J. Mol. Sci. 2023, 24, 2098 24 of 36
12. Miscellaneous Uses

A study was performed on M. oleifera using the HPLC-based cyclo condensation
method. Astragalin and isothiocyanates were used as markers for standardization of the
plant. The conclusive result of the study suggests that the standardized method might
be useful for assessing the quality of the development of cosmetic and natural health
products [144].
The extract of M. oleifera leaves was helpful in eliminating the adverse effects of neem
oil, which is used in aquaculture as an insecticide to control predators and parasites of fish
fry. The researchers concluded that the extract of M. oleifera leaves eliminated the oxidative
stress and toxicity caused by neem oil [145].
The lower yield of okra (Abelmoschus esculentus) was studied. The low production
of these crops was due to infestation by pests and insects and poor soil nutrient content. In
order to improve production conditions, different chemical pesticides were used, which
brought further environmental risks. The use of M. oleifera aqueous leaf extract at different
concentrations (1:30 and 1:40) proved beneficial for okra [146].
The efficacy of M. oleifera leaf and root extract was evaluated as a plant growth regu-
lator and biopesticide in the wheat harvest. The researcher used different concentrations
(5, 10, 12.5, 25% w/w, w/v, v/v) of Moringa leaf and root extract at different stages of
the wheat plant. Significant plant growth was observed, resulting in increased yield and
a decrease in aphid invasion [147].
M. oleifera is rich in macronutrients and micronutrients, vitamins, phytohormones,
alkaloids, and flavonoids, which make this plant a multipurpose plant. Recent research has
shown that Moringa extract is also helpful in tolerance to abiotic and biotic stress under
stressful environmental conditions [148].
The therapeutic effect of bioactive constituents (flavonoids, alkaloids, tannins, isothy-
ocyanin and beta-sitosterol) present in M. oleifera has been reported in chronic diseases
such as hyperlipidemia [149], hypertension [150], hepatoprotective [151], anti-cancer [152],
Alzheimer’s disease [153], Parkinson’s disease [154].
The combined effect of M. oleifera and praziquantel in rats was studied by a group
of researchers. The seeds and leaves of M. oleifera were considered to evaluate their
bioavailability with praziquantel and also the in vivo effects of the same were observed on
Taenia crassiceps. The study showed that the combined action of both had a significant
amount of cytocidal activity compared to the rats, which were only administered with
praziquantel [155].
A variety of bioactive nutrients, such as flavonoids and vitamins, is available in
the M. oleifera plant. The in vitro study conducted by a group of researchers focused on
bioactive compounds that make up the nutritional potential of plants [156]. The conclusive
statement of the researcher revealed that the high content of proteins, lipids, and sulfur-
containing amino acids and the relative lack of toxic components make moringa a great
nutritional alternative for humans [157].
The bioactive isolate palmitic acid from the leaf extract of Moringa has been attributed
to broad therapeutic benefits. A team of researchers studied this isolate against a wide
range of microbial and fungal strains. The results showed that it had the highest zone of
inhibition for both fungal and microbial strains [4].
The polyphenols and flavonoids present in M. oleifera to scavenge free radicals could
be useful in developing an anticancer drug delivery system. Nanoparticle technology was
used to incorporate Moringa extract as a drug carrier. Treatment of HeLa cell lines with
a single dose of the plant showed that the composite film of the plant extract was efficient
in killing malignant cells compared to other isolated and purified phytocomponents on the
market [158].
Int. J. Mol. Sci. 2023, 24, 2098 25 of 36
The bioactive components of M. oleifera inhibit the inflammatory markers in

lipopolysaccharide-induced human macrophages. The induced macrophages were treated
with M. oleifera extract. Thereafter the treated cells were tested for their anti-inflammatory
and cellular mechanism. The results revealed that the extract suppressed mRNA expres-
sion of IL -6, IL -1, NF-κB (P50), PTGS2, and TNF-α. At the same time, the inhibition of
phosphorylation of IκB-α and nuclear factor (NF)-κB was also observed in the study. The
researchers’ final statement suggests that the blocking of NF-κB and IκB-α may be the
reason for the inhibition of inflammation [159].
Apart from its wide use in preventing and curing various human diseases, Moringa is
known for a number of non-medicinal uses, chief among which is its use for poultry, espe-
cially in curing viral infections (Newcastle Disease Virus) and other parasitic and bacterial
diseases that cause mortality in animals [160]. The plant also serves as an important growth
promoter for farmers in the production of tomatoes, peanuts, corn, and wheat in their early
vegetative stages [161]. Environmentally friendly biopesticides are produced from this
plant, which is cheap and easily available and helps in curing various plant diseases [162].
Studies have shown that the total crop production increased by 20–35% by using M. oleifera
leaf extract, which is a good sign for increasing agricultural growth at a minimal cost [163].
The aqueous extract of M. oleifera is a source of various minerals and growth promoters
(indole acetic acid, gibberellins, cytokines). It thus can be used as an effective plant biostim-
ulant that could be a simple alternative to the artificial fertilizers and pesticides available
in the market [161]. The methanolic extract of the plant is found to be rich in potassium,
calcium, carotenoid, phenols, and zeatin, and when three sprays of this extract are applied
on the oilseed rape plant, it is observed that the pods, twigs, height, and number of seeds
increase significantly compared to the untreated control group [164]. The ability of the plant
to resist drought is due to the plant hormone “zeatin”, which is present in large quantities
in the methanolic extract, so the plants exposed to such climatic conditions when sprayed
with the methanolic extract of Moringa showed improved growth characteristics compared
with well-watered plants [165]. The tree is efficient in removing water hardness and is
used by African tribes as a cheap source compared to chemical softeners [166]. A study
conducted by several groups found that treating river water in African countries with
Moringa seeds reduced color and microorganisms by 90% and microorganism (Escherichia
coli) levels by up to 95%. Previous reports indicated that a water sample treated with
M. oleifera seeds reduced the hardness content of the water by 50–70%, which used to be
80.3 g L−1 CaCO3 [167]. It has also been shown to be an effective solution for treating
turbidity, alkalinity, and dissolved organic carbon. It is suggested that Moringa could be, to
some extent, an alternative to chemical alum used to remove water turbidity [168]. Moringa
is a good source for curing plant diseases and can be a good option for biopesticides [162].
Since various plant pathogens affect the plants, Pythium debaryanum-a pathogen responsi-
ble for damping-off disease-can be cured by adding leaves to the soil [169]. Nearly all plant
part (fruits, flowers, leaves, seeds, roots) is believed to have different properties that can
heal the body spiritually and psychologically [34].
13. Phytochemistry
Almost all parts of M. oleifera and its isolates have been studied for research. Based on
the literature collected between 2010 and 2022, more than 90 compounds from the genus
Moringa have been identified, many of which have therapeutic potential. The isolates fall
into the category of proteins and amino acids [170], phenolic acids [171], carotenoids [172],
alkaloids [173], glucosinolates [174], flavonoids [175], sterols [175], terpenes [176], tan-
nins and saponins [177], fatty acids [178], glycosides [179], and polysaccharides [180]
(Tables 4 and 5).
Int. J. Mol. Sci. 2023, 24, 2098 26 of 36
Table 4. Phytochemicals present in different plant part extracts of M. oleifera.
Extract Methanolic Ethanolic Methanolic Ethanolic Aqueous Methanolic Ethanolic Aqueous

S. No
Chemical Roots Roots Leaves Leaves Leaves Seeds Seeds Seeds
1. Alkaloid + + + + + + + +
2. Tannins + + + + + + - +
3. Flavonoids + + + + + - + -
4. Saponins + + + + + - + -
5. Terpenoids + + + + + - - -
6. Glycosides + + + + + - - -
7. Steroids + + + + + - - -
8. Coumarins - - + + - - - -
9. Proteins - - - - - + + -
10. Starch + + - - - - - -
Table 5. Select phytoconstituents of M. oleifera isolated through various techniques.
Constituents Concentrations # Category Technique Used Reference

LEAVES
Isoquercetin 1575.28 µg/g (w/w) Flavonoids UPLC-ESI-MS/MS [181]
Astragalin 0.153 µg/g (w/w) Flavonoids HPLC [182]
Isorhamnetin 2.9 mg/g (w/w) Flavonoids HPLC [183]
Daidzein ND * Flavonoid HPLC [183]
Apigenin ND * Aglycone HPLC [184]
Luteolin ND * Flavonoid HPLC [184]
Genistein ND * Flavonoid HPLC [184]
4-(α-L-rhamnopyranosyloxy) benzyl
33.9 mg/g Glucosinolates LC/MS [184]
glucosinolate
4-[(20 -O-acetyl-α-L-rhamnosyloxy)
21.84 to 59.4 mg/g Glucosinolates HPLC [184]
benzyl] Glucosinolate
Epicatechin 5.68 mg/g Flavonoid HPLC [184]
Ferulic acid 0.078 mg/g Phenolic acid HPLC [184]
Caffeic acid 0.409 mg/g Phenolic acid HPLC [184]
Ellagic acid 0.018 mg/g Phenolic acid HPLC & MS/MS [185]
Sinalbin 2.36 mg/g Glucosinolates HPLC [185]
Sinapic acid ND Phenolic acid HPLC &MS/MS [185]
Chlorogenic acid 0.018 mg/g Phenolic acid HPLC &MS/MS [185]
Gallic acid 1.034 mg/g Phenolic acid HPLC &MS/MS [186]
Salicylic acid 0.14 µg/g Phenolic acid HPLC GC MS [186]
Vicenin-2 193.43 ng/mg Flavonoid HPLC PDA [187]
Quercetin-3-O-(600 -malonyl)
ND * Flavonoid HPLC DAD [188]
glucoside
Pyrrolemarumine-400
NA ˆ Pyrole alkaloid NMR [189]
-O-α-Lrhamnopyranoside
4-[(40 -O-Acetyl-α-L-
2.16 to 5.0 mg/g Glucosinolates HPLC [190]
rhamnosyloxy)benzyl]
SEEDS
Niazimicin NA ˆ Isothiocyanates HPLC [173]
Niazirin NA ˆ Isothiocyanates HPLC [173]
ROOTS
Arachidic acid ND * Fatty acid GC-MS [190]
BARK
β-Sitosterol-3-O-β-D-
26.67 mg/g Glucoside HPTLC [190]
galactopyranoside
ND—not detected; NA—not available; * lower but appreciable amount present; ˆ compounds were isolated, but
data not available; # the concentration of the constituent may vary according to geographical location.
The leaves contain larger amounts of calcium, potassium, proteins, and amino acids
such as arginine and histidine [170].
Int. J. Mol. Sci. 2023, 24, 2098 27 of 36
M. oleifera leaves contain a higher concentration of phenolic acids and flavonoids,

including
M. oleiferacinnamic
leaves acid,
containsinapic acid, concentration
a higher syringic acid, gentisic acid,acids
of phenolic gallicand acid,flavonoids,
ferulic acid,
protocatechuic
including cinnamic acid,
acid, vanillin,
sinapiccaffeic acid, o- coumaric
acid, syringic acid,acid,
acid, gentisic p-coumaric
gallic acid, acidferulic
and epicate-
acid,
chin are phenolic
protocatechuic acids. Incaffeic
acid, vanillin, contrast,
acid,quercetin,
o- coumaric catechin, myricetin,
acid, p-coumaric acidandand kaempferol
epicatechinfall
areunder
phenolicthe category
acids. Inof flavonoids
contrast, havingcatechin,
quercetin, excellent myricetin,
therapeuticand activity and are fall
kaempferol listed above
under
theincategory
Table 2 [171,175,177].
of flavonoids having excellent therapeutic activity and are listed above in
Table 2 The carotenoid lutein is present in larger quantities in the leaves of M. oleifera [172].
[171,175,177].
The Thetherapeutic
carotenoidefficacy
lutein isofpresent
the plant is duequantities
in larger to the active leaves of M.present
in theconstituents oleifera [172].
in theThe plant
therapeutic
leaves. The efficacy
leavesofofthe theplant
plant is due to thenearly
revealed activethirty-five
constituents present inby
compounds thegas
plant leaves.
chromatog-
The leaves of the
raphy–mass plant revealed
spectrometry. nearlythe
Among thirty-five compounds
thirty-five by gas chromatography–mass
isolated compounds, some important ones
spectrometry. Among the thirty-five isolated compounds, some important
isolated in the leaves were palmitoyl chloride, cis-vaccenic acid, 5-O-acetyl-thio-octyl, ones isolated in
pregna-
the7-dien-3-ol-20-one,
leaves were palmitoyl chloride,
γ-sitosterol, cis-vaccenic acid, 5-O-acetyl-thio-octyl,
β-l-rhamnofuranoside, and tetradecanoic acid pregna-7-dien-
[178].
3-ol-20-one,
Two γ-sitosterol,
new alkaloids, marumoside A and and
β-l-rhamnofuranoside, tetradecanoic
marumoside B, wereacidalso[178].isolated from M.
Two leaves;
oleifera new alkaloids,
another type marumoside
of alkaloid, A and marumoside
aurnatiamide B, were
acetate was also isolated
isolated fromfrom M.
M. oleifera
oleifera leaves; another type of alkaloid, aurnatiamide acetate was
roots [173,178]. Moringin and moringinine are the two alkaloids present in the plant’s isolated from M. oleifera
roots
stem [173,178].
[179]. Moringin and moringinine are the two alkaloids present in the plant’s
stem [179].M. oleifera is a rich source of glucosinolates. The most abundant glucosinolate present
in M.theoleifera
species is aisrich source of glucosinolates. The most abundant
4-O-(α-L-rhamnopyranosyloxy)-benzyl glucosinolate
glucosinolates, present as
also known
in glucomoringin
the species is 4-O-(α-L-rhamnopyranosyloxy)-benzyl
[174]. glucosinolates, also known as
glucomoringin [174].
A sterol isolate, β-sitosterol was found in seeds and leaves of M. oleifera [173]. Another
typeA sterol
of sterolisolate, β-sitosterol
glycoside was found in seeds and leaves of was
β-sitosterol-3-O-β-D-galactopyranoside M. oleifera
extracted[173]. fromAn-M.
other type of sterol
oleifera bark [174,175]. glycoside β-sitosterol-3-O-β-D-galactopyranoside was extracted from
M. oleiferaAn bark [174,175].
interesting category of diterpenes and terpenes is found in M. oleifera leaves.
An interesting
Among which Phytol category of diterpenes
is diterpene alcohol, aand terpenes
major is found
component in M. oleifera
of chlorophyll, andleaves.
is found
Among which Phytol is diterpene alcohol, a major component of
abundantly in leaves of the plant. At the same time, terpenes and their derivatives are chlorophyll, and is found
abundantly
present inin leaves
trace of the (linalool
amounts plant. Atoxide,the same time, terpenes
farnsylacetone, and their derivatives
isolongifolene α-ionene, and are α-
present in trace amounts (linalool oxide, farnsylacetone, isolongifolene α-ionene, and α-
and β-ionone), whereas hexahydro-farnesyl acetone can be found in abundance [176].
and β-ionone), whereas hexahydro-farnesyl acetone can be found in abundance [176].
Seed oil extract of M. oleifera commonly contains tannins and saponins, which are
Seed oil extract of M. oleifera commonly contains tannins and saponins, which are
responsible for numerous pharmacological activities [177].
responsible for numerous pharmacological activities [177].
Fatty acids such as arachidic acid, octacosanoic acid, oleic acid, palmitic acid, stearic
Fatty acids such as arachidic acid, octacosanoic acid, oleic acid, palmitic acid, stearic
acid, linolenic acid, behenic acid, and paullinic acid are found in M. oleifera seeds [178].
acid, linolenic acid, behenic acid, and paullinic acid are found in M. oleifera seeds [178].
Two glycosides, namely niazirin and niazirinin were extracted from the ethanolic ex-
Two glycosides, namely niazirin and niazirinin were extracted from the ethanolic
tract of M. oleifera [179].
extract of M. oleifera [179].
The exudate of the gum contains a large number of poly saccharides such as D-ga-
The exudate of the gum contains a large number of poly saccharides such as D-
lactose, L-arabinose, D-xylose, L-rhamnose, D-mannose, and -glucuronic acid [180]. The
galactose, L-arabinose, D-xylose, L-rhamnose, D-mannose, and -glucuronic acid [180]. The
structure
structure of of
somesome of of
thethekeykey phytoconstituentsisolated
phytoconstituents isolatedfrom
fromM. M.oleifera
oleiferaisisshown
shownininFigureFigure7.7.
Figure 7. Cont.
Int. J. Mol. Sci. 2023, 24, 2098 28 of 36
Figure Structure
7. 7.
Figure ofof
Structure some key
some phytoconstituents
key isolated
phytoconstituents from
isolated M.M.
from oleifera.
oleifera.
14.14.Current
CurrentStatus
Status
Moringa
Moringaisisa aversatile
versatileplant
plantwith
withnumerous
numerousbenefits,
benefits,and
andthe
thecurrent
currentstatus
statusofofthe
the
plant suggests that it can be used in various pharmacological activities
plant suggests that it can be used in various pharmacological activities and their and their related
related
formulations,
formulations,biomedical
biomedical applications,
applications,livestock, poultry,
livestock, and fish
poultry, andproduction, enormously.
fish production, enor-
Extensive research conducted in India, Nigeria, Brazil, and China during
mously. Extensive research conducted in India, Nigeria, Brazil, and China during 2019– 2019–2022 has
created a valuable resource for researchers worldwide. After an extensive study
2022 has created a valuable resource for researchers worldwide. After an extensive study of this plant,
it of
was found
this that
plant, M. oleifera
it was foundhas
thatevolved to benefit
M. oleifera humanstoinbenefit
has evolved many ways.
humans A large
in manynumber
ways.ofA
nutrients and phytoconstituents in this plant make it suitable for consumption
large number of nutrients and phytoconstituents in this plant make it suitable for con- by humans
and animals.by
sumption Due to its high
humans and anti-oxidant
animals. Dueproperties,
to its highitanti-oxidant
has become aproperties,
pharmaceutical
it has option
become
fora the
pharmaceutical option for the production of formulations such as wound healing, etc.
production of formulations such as wound healing, anti-cancer, and anti-ageing anti-
It is suitable not only for human use but also as a fertilizer in various forms extracted from
cancer, and anti-ageing etc. It is suitable not only for human use but also as a fertilizer in
M. oleifera. Besides its benefits, it also has severe toxic and abortifacient effects when taken
in large quantities.
Int. J. Mol. Sci. 2023, 24, 2098 29 of 36
15. Conclusions and Future Perspective

The review summarizes various aspects of M. oleifera, including its worldwide research,
ethnopharmacology, pharmacology activities, phytochemistry, phytopharmaceutical for-
mulations, clinical studies, toxicology, and other miscellaneous parameters. The presence of
alkaloids, phenolic acid, glycosides, sterols, glucosinolates, flavonoids, terpenes and fatty
acids are responsible for the medicinal effects of M. oleifera. In addition, M. oleifera is also
rich in compounds such as vitamins, micronutrients, and carotenoids which increase its
medicinal value and consumption as a superfood. Pharmacological studies show that the
active constituents of the plant have effectively cured various diseases such as neuropathic
pain, cancer, hypertension, diabetes, obesity etc. Nevertheless, several phytochemicals have
yet to be explored for their possible therapeutic benefits. In addition to its clinical use, the
plant is also used as an effective biostimulant for farmers in their fields and has proven to
be a cost-effective alternative. A literature survey suggested that much preclinical research
has been carried out in the last few years. In the future, more clinical studies are required
to investigate the efficacy of the plant in life-threatening diseases such as coronavirus out-
breaks, an acquired immunodeficiency syndrome (AIDS), and various cancers. Moreover,
further mechanism base studies are also proposed to explore the mechanistic approach
of the plant to identify and isolate active or synergistic compounds. Overall, M. oleifera
signifies its name, “Miracle tree,” and appears to be a phytopharmaceutical and functional
food that, if consumed daily, can potentially treat various chronic diseases in humans and
could be used by medical practitioners as a safer alternative to treat various ailments.
Author Contributions: Conceptualization, A.P. (Ashutosh Pareek); methodology, A.P. (Aaushi Pa-
reek) and M.P.; software, M.P.; writing—original draft preparation, M.P., P.K., V.J., M.M.G. and A.P.
(Aaushi Pareek); validation, Y.R., A.A.C. and M.P.; writing—review and editing, A.P. (Ashutosh
Pareek), A.A.C., Y.R. and M.M.G.; supervision, A.P. (Ashutosh Pareek); project administration, A.P.
(Ashutosh Pareek) and A.A.C. All authors have read and agreed to the published version of the
manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Acknowledgments: The authors are grateful to Banasthali Vidhyapith for providing all the necessary
resources for completing this report. The authors also thank Brijmohan Bairwa, Department of
Remote Sensing, Banasthali Vidyapith, for technical support during the geospatial analysis.
Conflicts of Interest: The authors declare that they have no conflict of interest with respect to research,
authorship, and/or publication of this article.
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International Journal of

1 Department of Pharmacy, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India

Int. J. Mol. Sci. 2023, 24, 2098. https://doi.org/10.3390/ijms24032098 https://www.mdpi.com/journal/ijms

2.2. Software and Techniques Used

3. Worldwide Research and Collaboration

Int. J. Mol. Sci. 2023, 24, x FOR PEER REVIEW 4 of

International studies on M. oleifera involve the collaboration of scientists from coun-

Table 1. Uses of Moringa oleifera listed in Ayurvedic medicinal textbook.

Name of Ayurvedic Text Form of Plant Used Treatment References

Plant part Compound Class Structure Therapeutic Activity References

Plant part Rutin

Plant part Compound Class Structure Therapeutic Activity References

Exerts an excellent effect as anti-diabetic

Int. J. Mol. Sci. 2023, 24, 2098 7 of 36

Plant part Compound Class Structure Therapeutic Activity References

Plant Part Myricetin

Int. J. Mol. Sci. 2023, 24, x FOR PEER REVIEW 9 of 40

Plant part Compound Class Structure Therapeutic Activity References

Ellagic acid Prevents viral and bacterial infections,

Boosts athletic performance, reduces fatigue,

Int. J. Mol. Sci. 2023, 24, 2098 8 of 36

Int. J. Mol. Plant

Int. J. Mol. Sci. 2023, 24, x FOR PEER REVIEW 10 of 40

Plant part Compound

Gallic acid Anti-inflammatory, anti-neoplastic,

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Plant part Compound Class Structure Therapeutic Activity References

Plant Part Compound Class Structure Therapeutic Activity References

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Anti-inflammatory, pain relieving,

Seeds β-sitosterol Phytosterol Anti-inflammatory [63]

Plant part Compound Class Structure Therapeutic Activity References

Seeds Procyaniadin Flavonoid Cardioprotective [68]

Treatment of deficiency caused by genetic

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Plant Part Compound Class Structure Therapeutic Activity References

8.1. Antimicrobial and Antifungal Activity

8.2. Anti-Inflammatory Activity

8.3. Oxidative Stress

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Figure 4. M. oleifera, as an oxidative and inflammatory marker, inhibits IKBα phosphorylation,

8.6. Fertility and Anti-Fertility Activity

8.7. Hepatoprotective Activity

8.8. Cardiovascular Activity

8.9. Anti-Ulcer/Gastroprotective Activity

8.10. Analgesic/Antipyretic Activity

8.11. Neuropharmacological Activity

8.13. Wound Healing Effect

8.14. Immunomodulatory Activity

8.15. Hematological Activity

8.16. Anti-Obesity Activity

8.19. Diuretic Activity

8.20. Angiotensin Converting Enzyme (ACE) Activity

8.21. Anti-Venom Effect

8.22. Cytotoxicity Effect

10. Clinical Trials