Matrix Science Pharma (MSP) 1(1) (2017) 17-26

ISSN: 2521-0815 (Print)

ISSN: 2521-0432 (Online)
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Matrix Science Pharma (MSP)
Journal Homepage: http://www.razipublishing.com/journals/matrix-science-pharma-msp/

Bioactive Compounds from Medicinal Plants and Their Importance in Drug Discovery
in Pakistan
Ghulam Mustafa1,2*, Rawaba Arif1, Asia Atta3, Sumaira Sharif4 and Amer Jamil1
1
Department of Biochemistry, University of Agriculture, Faisalabad-38040, Pakistan
2
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad-38000, Pakistan
3
Department of Biochemistry, Bahauddin Zakariya University, Multan-60800, Pakistan
4
Department of Biochemistry and Molecular Biology, University of Gujrat, Gujrat-50700, Pakistan
*Corresponding author: [email protected]
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
ARTICLE DETAILS ABSTRACT
Article history: Humans have relied on nature throughout their ages to cater for their basic needs including medicines to cure
a wide spectrum of diseases. Plants have formed the basis for sophisticated systems of traditional medicines.
Received 22 January 2017
For therapeutic agents many of the presently known lead compounds are natural products or their derivatives.
Accepted 03 February 2017
Available online 05 February 2017 Ethnomedicinal studies play a vital role to discover new drugs from indigenous medicinal plants. Green
pharmaceuticals are getting popularity and extraordinary importance because vast opportunities for new drug
Keywords: discoveries are provided by the unmatched availability of chemical diversity and natural products either as pure
compounds or as homogenous plant extracts. Therefore, in recent years the demand for herbal medicines and
medicinal plants; northern areas;
several natural products from a variety of plant species is consistently increasing. In spite of being an agricultural
Cholistan desert; secondary metabolites;
biochemical profiling country and having different ecological regions, the medicinal plants of Pakistan have not been explored for their
secondary metabolites which are responsible for treating different diseases. Although, huge importance of different
extracts of medicinal plants from Pakistan have been reported for their different activities such as antimicrobial,
anti-cancerouse, antiviral and antioxidant but complete biochemical profiling of these medicinal plants is lacking.
LC-MS and GC-MS techniques have been applied in the field of drug discovery from medicinal plants but in Pakistan
its success rate is very low in the subject of biochemical profiling. Therefore, such techniques should be used in
Pakistan to explore active constituents from medicinal plants which could be used as medicines in future.

1. Role of plants in drug discovery thousands of years [14]. Beginning with morphine which was isolated from
opium in the early 19th century, now active compounds are also isolated
Medicinal plants have been used as a source of medicine in all cultures from medicinal plants [14-15]. Earlier, when the role of medicinal plants in
since times immemorial [1]. Initially plants were used by the people to drugs was discovered then a number of drugs were isolated such as codeine,
meet their nutritional requirements. The natural flora became a very useful cocaine, quinine, digitoxin and morphine. Some of these drugs are still in
source for health improvement and to cure many diseases across various our use [14,16]. The extracts of several medicinal plants are very effective
human communities and a variety of plants species are offered which are against microbial as well as parasitic infections [17]. For example, several
still in use in many parts of the world such as Asia [2], South America [3] groups of antifungal proteins like glucanase, chitinase and proteins which
and Africa [4] for remedies against several diseases. Even though World are of low molecular weight and non-enzymatic in nature are present in the
Health Organization reported that the primary health care system for the seeds of many medicinal plants and these proteins are being used for the
60% population of the world is represented by the traditional medicines protection of a developing embryo from many infections [18].
yet a great number of plant species with potential biological activities were Importance has been given to ethnobotany field in Pakistan [19] and a few
unexplored [5]. The effectiveness of traditional medicines is now a putative studies have been done recently [20-21] but the treasure of medicinal plants
fact because of their better compatibility with human body, better cultural is being vanished with the passage of time and measures are still needed
acceptability in all over the world and lesser side effects [6]. In various to save it [21]. Pakistan is very rich in botanical wealth and has variety of
human cultures around the world more than 35,000 plant species are being medicinal and aromatic plants because of its exceptional phytogeography
used for their medicine purposes [7] and for primary health care nearly with varied climatic and edaphic factors such as soil conditions and multiple
80% of the world populations rely on these traditional medicines which ecological regions. Out of 5700 about 400–600 species of medicinal plants
include the use of plant extracts most of the time [8]. are estimated to be found in Pakistan and only a small percentage of which
Ethnomedicinal studies play a vital role to discover new drugs from have been biochemically investigated [22]. In the early 1950s, for their
indigenous medicinal plants and green pharmaceuticals are getting basic healthcare needs about 84% population of Pakistan was relying on
popularity and extraordinary importance [9] because vast chances traditional medicines [13] but now due to modernization and urbanization
for new drug discoveries are provided by the unrivaled availability of the practice is limited only in the remote areas [23]. Most medicinal plants
chemical diversity and natural products either as pure compounds or as from Pakistan are confined to the mountainous areas and then desert areas.
homogenous plant extracts [10]. A decade ago the synthetic drugs because A total of 1572 genera and 5521 species are identified in Pakistan having
of unanticipated side effects were approved as safe and effective and had to medicinal values for many diseases [24]. To enlist the applications of these
be recalled and relabeled. The herbal medicines on the other hand, have no indigenous medicinal plants a very few attempts have been made [25] and
such adverse effects and because of combinations of medicinal constituents the information is incomplete as very few common plants are listed.
coupled with minerals and vitamins have benefits over synthetic ones [11].
In current scenario, the attention of scientists has been diverted towards 2. Biochemical profiling and related techniques
ethnomedinices due to the revival of knowledge in customary health
practices throughout the world. Therefore, in recent years the demand In an organism the presence of complete complement of small molecules
for herbal medicines and several natural products from a variety of plant is called metabolome [26]. Various terms such as metabolomics,
species is consistently increasing. A number of modern drugs have been metabonomics, metabolic fingerprinting and metabolic profiling have
discovered since the history of ethnobotany paying a distinct importance been defined throughout the years. The variations in metabolite fluxes
to the documentation of traditional information of medicinal plants. From are revealed by metabolomics and therefore it is the decisive level of post-
medicinal plants 78% of new chemical constituents being natural or natural genomic analysis. Minor changes within gene expression is responsible
product-derived molecules are being used as a promising alternative to control these metabolite fluxes and transciptomics and/or proteomic
treatment for infectious diseases [12]. In modern pharmacopeia about 25% analysis are the methods to measure these changes while the analyses
drugs and also a great number of synthetic analogs prepared on proto-type reveal post-translational control over the activity of enzyme involved. The
compounds which have been derived from plants are included [13]. high-throughput qualitative screening of a tissue or an organism with an
Plants have an immense importance in the field of medicines because they analysis of sample comparison and discrimination as a main objective is
have been utilized in medicines for the treatment of so many diseases for called metabolite fingerprinting [26]. The biochemical status of an
Cite this article as: Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil. Bioactive Compounds from Medicinal Plants and Their
Importance in Drug Discovery in Pakistan / Mat. Sc. Pharm 1(1) (2017) 17-26
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Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil/ Matrix Science Pharma 1(1) (2017) 17–26

organism is revealed by the measurements of intracellular metabolites called “semi-synthetic drugs” some natural products derived from plants
which would be qualitative or quantitative. These measurements in turn have been modified marginally to make them more effective or less toxic
can be used to assess and monitor the functions of different genes [27]. [39]. In 1953 aspirin was developed as an example to such type of tactic
Different approaches are used to detect and investigate metabolome. For with the help of structural modification of salicylic acid that was observed
metabolic fingerprinting, liquid chromatography–mass spectrometry (LC- as an active constituent in many medicinal plants known for having pain-
MS) and proton nuclear magnetic resonance (1H NMR) are frequently used relieving effects [47]. Guanidine-type of alkaloid, galegine in G. officinalis
techniques. In various fields of plant research, LC-MS as a technique for has blood glucose lowering property and because the alkaloid was found
fingerprinting was applied such as plant biochemistry [28], food chemistry to be very toxic for human use therefore, a number of structural analogs of
[29], chemotaxonomy [30] and for establishing a control over quality of this alkaloid were made and tested clinically. These efforts resulted in the
medicinal plants [31]. Over the past 50 years, spectroscopic techniques development and marketing of metformin which is an effective antidiabetic
coupled with some good extraction methods like chromatography have drug [45].
contributed natural product chemistry to a phenomenal success. Gas
chromatography (GC) and liquid chromatography coupled to mass 4. Bioactive compounds from medicinal plants
spectrometry (GC- and LC-MS) are the most suited equipment for fast and
comprehensive analysis of ultracomplex metabolite samples [32]. Using The extracts of several medicinal plants are very effective against
LC the separation of the thousands of molecules present in biofluids can microbial as well as parasitic infections [17]. For example, several groups
reduce ion suppression [33] by decreasing the number of competing of antifungal proteins like glucanase, chitinase and proteins which are of
analytes entering the mass spectrometer ion source at a time. This results in low molecular weight and non-enzymatic in nature are present in the
a selective approach that allows quantification and structural information, seeds of many medicinal plants and these proteins are being used for the
where sensitivities in the pg/mL range can be achieved readily [34]. LC/MS protection of a developing embryo from many infections [18]. Shoemaker
technique has replaced some of the specialized methods which have been et al. [48] has reported that there are over 400,000 species of plants on
practicing in traditional clinical laboratories [35] that used immunological, earth which have a huge reservoir of bioactive compounds, but only a small
fluorometric, and biological techniques [36]. High sensitivity and selectivity percentage of these have been examined in the research studies. When the
are the main advantages of LC/MS that allow quantitative analysis bioactive compounds from traditional medicinal plants were investigated
of secondary metabolites in complex biological matrices at very low through screening programs, it resulted that these compounds possessed
concentrations [37]. a considerable number of therapeutic properties. As a consequence a
number of antitumoral drugs [49] and antifungal agents [50] are available
3.History of medicinal plants for clinical uses and have been derived from plants. In another study [51],
it has also been reported that plants are an important and continuous
Botanical medicine or phytomedicine, also called herbal medicine is the use source of anticancer agents. During last 10-15 years, the fungal pathogens
of plants’ seeds, roots, berries, leaves, flowers or bark for healthcare and have gained resistance against presently engaged antifungal drugs and the
they have been used since the prehistoric times by the people worldwide to adverse reactions or toxicity of the anti-infective. Due to this reason the
treat, control and manage a variety of diseases [38-39]. Today, the infectious importance of medicinal plants has been increased because they possess
diseases have become worldwide a leading cause of death, therefore, their antimicrobial and antifungal activities [52].
study has become a global concern [40]. The emergence of multidrug-
resistance in the pathogens is threatening the clinical efficiency of many Several epidemiological studies have shown that certain dietary elements
existing antibiotics [41]. It is a matter of fact that a number of infectious play an important role in the prevention as well as in the etiology of
diseases have been treated with herbal medicines throughout the history different types of human cancers. The people who use plant-derived
of mankind. Due to incomparable availability of the chemical diversity, foods in great amounts such as vegetables, fruits and soybeans have less
the plant extracts either as standardized natural products or as pure chances of cancer [53]. Although documentation was limited but it was
compounds have been providing unlimited prospects for new drugs. It is observed experimentally that the preparations of certain plants may cure
an urgent and continuous need that new antimicrobial compounds should many diseases [54]. Stem parts of Euphorbia candelabrum plant has been
be discovered having novel mechanisms of action and diverse chemical used against Newcastle Disease (ND) in poultry while the leaves of Iboza
structures for re-emerging and new infectious diseases [42]. Therefore, the multiflora in combination with Capsicum annuum fruits have been used to
attention of a number of researchers towards folk medicines is increasing cure ND as well [54]. Mtambo et al. [55] reported that in a local preparation in
continuously and they are trying to develop better drugs with antimicrobial Northern Tanzania consisting of three plants, namely Capsicum frutescens,
activities [43]. A continuous increase in the failure of antibiotic resistance Citrus limon and Opuntia vulgaris possess a therapeutic efficiency against
and chemotherapeutics exhibited by the pathogenic microbial infectious ND in commercial chickens. In parasites and pathogenic microbes, the
agents has enhanced the importance of medicinal plants and they have been development of multi-drug resistance and for systemic mycoses the non-
screening out for their potential antimicrobial activity [44]. availability of safe antifungal drugs has forced the researchers to look
Scientists began to isolate, purify and identify active constituents (principles) for new antimicrobial substances from some other sources, including
from medicinal plant extracts during the late nineteenth century and these plants. The medicinal plants which have been used traditionally produce
efforts led them to find some of the vital drugs from medicinal plants which a wide range of compounds with known therapeutic values [56]. For the
are still broadly used in the field of modern medicine [45]. production of new antimicrobial drugs, those substances are considered
the most which have little toxicity to host cells and can inhibit pathogens.
Table 1. Medicinal plants which laid the foundation of drug discovery The antimicrobial properties of medicinal plants from South Asia have been
increasingly reported [57-58]. In the local traditional systems of medicines,
most of these medicinal plants have been used to cure different ailments
including infectious diseases [56]. For instance, Terminalia arjuna bark
has been extensively used for a variety of purposes and particularly, the
bark has been effectively used in cardiovascular therapy [59]. Similarly,
Andrographis lineate has been used for the treatment of snake bites [60].

5. Herbal medicines today

Various methods have been used to obtain compounds for drug discovery
including isolation and purification of active compounds from medicinal
plants and other natural sources, combinatorial chemistry, synthetic
chemistry and bioinformatics approaches (e.g. molecular modeling) [61].
Although the pharmaceutical companies and funding organizations are
getting interested towards combinatorial chemistry, molecular modeling
and other synthetic chemistry techniques but natural products and
particularly medicinal plants remain an important source of new drugs,
Other than the biologically active natural products derived from medicinal new chemical entities (NCEs) and new drug leads [16].
plants stated above, a great number of natural products derived from
medicinal plants have also served as “lead compounds” to design, synthesize Mostly the plant medicines have been used in their crude forms before
and develop novel drug compounds [47]. In this perspective, to prepare so nineteenth century and administered as infusions (herbal teas),

Cite this article as: Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil. Bioactive Compounds from Medicinal Plants and Their
Importance in Drug Discovery in Pakistan / Mat. Sc. Pharm 1(1) (2017) 17-26
 19
Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil/ Matrix Science Pharma 1(1) (2017) 17–26

decoctions (boiled extracts of bark and root), tinctures (alcoholic extracts)

and syrups [62]. Plants have also been applied externally as herbal washes
and ointments (essential oils, poultices and balms) [46]. Researchers in
developing countries who work on medicinal plants often experience a
comprehensive exercise for the learning of names, uses and preparations
of native plants [63], and in a number of marketplaces of villages of such
countries the medicinal plants are being sold along with vegetables and
other goods. The World Health Organization (WHO) has also recognized
that in developing countries the agenda for effective health can never
be accomplished by western medicine alone therefore it should be
supplemented by other medicines which also include traditional herbal
medicines of these countries [64]. It has also urged and advised accordingly
to utilize the resources of their medicinal plants and other systems of
traditional medicines to accomplish primary healthcare goal. It is reported
for developed countries that the patients of chronic diseases are turning
towards herbal treatments as alternatives to modern synthetic drugs
[65]. In developed countries this interest in the use of herbal medicines is
believed to be motivated by several factors which include:
i. The effectiveness of herbal medicines: Medicinal plants are believed
to be effective, gentle and most of the time specific in their function to
organs or systems of human body, and the belief that herbal medicines can
be used to treat certain diseases where conventional medicine fails [44].
ii. Side effects of synthetic drugs: Although synthetic or chemical drugs
as compared to herbal medicines can have greater or quicker effects but
they possess many adverse effects and risks. Herbal medicines are believed
to be devoid of these adverse effects because millions of people around
the world have been using herbal medicines against many diseases for
thousands of years [66]. 7. Medicinal plants from Northern areas of Pakistan
iii. Synthetic drugs are highly costly: Herbal medicines are generally
less expensive as compared to synthetic ones. The northern most tracts of Pakistan cover an area of 72,486 sq. km, border
Medicinal plants are continuously contributing to modern prescription the Indian-administered Jammu and Kashmir to the east, Central Asia and
drugs considerably by providing principal constituents which can be used Afghanistan through the Wakhan Corridor to the west, Chinese province of
to synthesize new drugs. Xinjiang to the north and Pakistan-administered Azad Jammu and Kashmir
to the south. The Northern areas are divided into six districts. Gilgit region
From medicinal plants the search and use of drugs and dietary supplements has four districts which include Astore, Ghizer, Diamer and Gilgit. Baltistan
have been hastened in the recent past. Biochemists, microbiologists, region has two districts which include Ghangche and Skardu (Fig 1). Being
botanists, pharmacologists and chemists of natural products around the a multidisciplinary, ethnobotany has not been given much importance in
world are engaged to investigate medicinal plants for geting more and more Northern areas of Pakistan although they have ample scope in this field.
phytochemicals and lead compounds which could be developed to treat However, recently these studies have started to gain momentum [74].
different diseases.

6. Herbal medicine in Pakistan

In developed countries although the direct use of medicinal plant extracts

continued to decrease in the late nineteenth and early twentieth centuries
but in many parts of the world the medicinal plants are still playing a very
important role in healthcare systems [67]. According to World Health
Organization [68] for primary healthcare needs, 60% of world’s population
is dependant on traditional medicines and 80% population of developing
countries is depending almost completely on traditional plants to get herbal
medicines [69]. To the present day, the long tradition of herbal medicine
continues in China, India, Pakistan and many other African and South
American countries [70-71]. Pakistan is very rich in botanical wealth
and diversity of plants resources because it has different climatic and
edaphic factors. Only a small percentage of plants have been investigated
biochemically [22] and now an extraordinary importance and popularity is
being received by green pharmaceuticals [72].
In Pakistan, the major research activities on medicinal plants are on the Fig 1. Map of Northern areas of Pakistan (internet source)
level of documentation and the research works are being conducted mostly
in universities as ethnobotanical listing of resources. There are a number A great treasure of medicinal plants is present in northern areas of Pakistan.
of research institutes in Pakistan which are involved in survey to various Leporatti and Lattanzi [75] studied 27 medicinal plants ethenobotanically
kinds of analytical studies. In Table 2, a list of some known organizations in Makran and discussed their traditional medicinal uses. Goodman and
is given which are involved in medicinal plants research. The knowledge Ghafoor [76] conducted ethenobotanical study in Balochistan province. It
of local communities of the country about traditional uses of medicinal is the region where a heterogeneous cultural group known as Baloch lives.
plants occurring in their areas are centuries old which has been transferred They collected information about 114 plant species used by nomads and
from generation to generation. These indigenous plants are used for the village dwellers. Shinwari [77] focused on information regarding traditional
treatment of almost any kind of disease including headache, stomachic, cut uses of plants of Kaghan valley. Dastagir [78] reported the medicinal plants
and wound [73]. For the extraction of various types of active constituents, of Mai Dhani Hill, Muzaffarabad (AK). Bukhari [79] reported that as many as
some of the important plants are commercially harvested. 69 plant species are used as crude drugs by the local people and folk lore for
treating various diseases in National Park Machayara Muzaffarabad (AK).
Table 2. Major organizations of Pakistan involved in medicinal plants Khan [80] reported phytosociological study in Babusar valley and recorded
research five plant communities in Babusar valley, district Diamer. He also described
the vegetation type, range management and medicinal plants of the area.
Rasool [81] studied the medicinal plants conservation status of Northern
areas and recorded 60 medicinal plants from different locations of Northern
areas. Gorsi and Shahzad [82] reported the medicinal uses of plants by the
local community in Dhir Kot, district Bagh (AK). Local people collect

Cite this article as: Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil. Bioactive Compounds from Medicinal Plants and Their
Importance in Drug Discovery in Pakistan / Mat. Sc. Pharm 1(1) (2017) 17-26
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Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil/ Matrix Science Pharma 1(1) (2017) 17–26

medicinal plants for use as home remedies at large. Information about Fig 2. Map of Cholistan desert of Pakistan (Source: [89])
the collection, quantities and uses of the plants are badly needed to be Medicinal plants from neighboring countries that share habitats similar
communicated. to Cholistan especially from India have been explored for their medicinal
Importance has always been given to therapeutic plants as a mode of properties and traditional uses. Although, a great number of medicinal
treatment for different diseases in local cultures. Plants have also played plants from Cholistan desert have been frequently used the local people but
a vital role for the discovery of modern day medicines with novel chemical unfortunately, the active constituents from these plants with their medicinal
compounds [83]. Although the effectiveness of medicinal plants is often properties have still not documented [89]. Neurada procumbens is one of
accounted for curative purposes in terms of organic constituents they the most conspicuous examples and a great deal of mistreatment of this
possess such as vitamins, oils and glycosides but it is also an established important medicinal plant has made its indigenous status endangered to
fact now that the over dose or prolonged intake of some medicinal plants a critical level.
would lead to chronic accumulation of various elements that cause different
health problems [84]. Traditional uses of some commonly used medicinal
The treasure of medicinal plants in Pakistan has never been preserved
plants by local people of Northern areas are given in Table 3.
which causes loss of very important medicinal plants. Therefore, there
is a need to take steps for the conservation of these important medicinal
Table 3. Some medicinal plants from Northern areas with their
plants. In addition to Government of Pakistan, local people who are working
traditional uses
on medicinal plants should also follow guidelines for the collection and
harvesting of these important medicinal plants. N. procumbens has been
extensively used as a strong stimulant and strong tonic against weakness
and impotency besides as a cooling agent [90]. The serious threat to the
diversity of medicinal plants in Cholistan is from habitat degradation
because of agricultural practices. The farmers cultivate their desirable crops
and destroy or ignore other important plant species. There is an urgent
need for the conservation of medicinal plants in Cholistan by sustaining
natural habitat. The existing knowledge and documentation of medicinally
important plants should be promoted. The local communities of this region
also exploit these plant species for different purposes such as food, fodder
and construction. One such example is of Prosopis cineraria whose seeds
and fruits are used extensively in various dishes [91]. The herbal aqueous
extract of Cymbopogon jwarancusa is used by the people of Cholistan in
summer for relaxing and reducing thirst. Calotropis procera is another
important medicinal plant whose each and every part is used by the local
communities to cure various diseases and some part of this plant have other
applications such as fruit floss are used in pillows and cushions for stuffing
[92].

There are a great number of other examples of local medicinal plants from
Cholistan desert whose applications along with their chemical constituents
are not yet reported. Although there is a big list of medicinal plants which
are traditionally used by the local people of Cholistan desert but applications
of some commonly used medicinal plants by these people are given in table
4. Local names of these medicinal plants along with parts which are used to
cure different diseases are also given in the table.

Table 4. Some medicinal plants from Cholistan desert with their

traditional uses

8. Medicinal plants from Cholistan desert of Pakistan

In the southeastern part of the Indus plain from eastern Bahawalpur to

southern Thar Parkar region there is a typical desert which is an extension
of Thar Desert present between Pakistan and India. The desert is separated
by dry bed of the river Ghaggar from central irrigated zone of plains in
Bahawalpur and eastern Nara canal in Sindh. In Bahawalpur the desert in
known as Cholistan or Rohi and in Sindh it is called as Thar or Pat desert.
The surface of Cholistan desert is a wild maze of sand dunes and ridges.
Along the south border of Punjab province Cholistan desert is stretched
(Fig 2) and it a part of world’s seventh largest desert also known as the
Great Desert [86] which lies at an altidue of 112 m above the sea level [87].
Comprising an area in total about 25,000 km2 Cholistan desert lies between
27º 42’ and 29º 45’ North and 69º 52’ and 75º 24’ East [88].

Cite this article as: Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil. Bioactive Compounds from Medicinal Plants and Their
Importance in Drug Discovery in Pakistan / Mat. Sc. Pharm 1(1) (2017) 17-26
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Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil/ Matrix Science Pharma 1(1) (2017) 17–26

9. Secondary plant metabolites with medicinal properties

The pharmacological and medicinal properties of medicinal plants are often

attributed to the presence of so called secondary plant metabolites [116].
Unlike the presence of universal macromolecules of primary metabolism
(e.g. monosaccharides, polysaccharides, proteins, nucleic acids, lipids and
amino acids) in all plants, the secondary metabolites which have medicinal
properties are observed only in a few species of plants [117]. Against
herbivores and pathogens some of these secondary metabolites play a role
as defensive compounds while others function in attracting pollinators
and fruit dispersers, in reducing the growth of nearby competing plants, in
mechanical support for plants or in absorbing harmful ultraviolet radiation
[118]. Polysaccharides, waxes and fatty acids, terpenoids, phenolics (simple
Ethnopharmacological applications of some medicinal plants of Pakistan phenolics and flavonoids), alkaloids and glycosides and their derivatives
along with knowledge of their phytochemicals are given in table 5. are plant secondary metabolites which have reported medicinal properties
but not limited to these compounds only. Some of these plants secondary
Table 5. Ethnopharmacological applications of some medicinal plants metabolites are discussed here briefly:
along with their phytochemicals
i). Carbohydrates and related compounds
Fibre, cellulose and its derivatives, dextrins, fructans, pectins, starch
and its derivatives, mucillages (uronic acid containing polymers) and
gums are carbohydrates and related compounds derived from plants
[119]. Carbohydrates and related compounds in addition to their use in
pharmaceutical industry as bulking agents have also been shown to have
immune-modulatory, hypoglycaemic, anticoagulant (e.g. heparin), anti-
tumor and antiviral activities [46].

ii). Alkaloids
Alkaloids contain nitrogen in a heterocyclic ring are organic bases and many
of them have pronounced pharmacological activities [120]. On the basis of
either their basic ring system (e.g. atropine, quinoline, indole, isoquinoline,
piperdine alkaloids or imidazole) or plant sources (e.g. opium, vinca,
belladonna, ergot alkaloids or cinchona) or pharmacological properties (e.g.
analgesic, anti-malarial alkaloids or stimulant) alkaloids can be classified
into several groups [116]. Mostly, alkaloids are strongly bitter in taste and
are very toxic, for these reasons they are used by plants to defend them
against herbivores, microbial pathogens and invertebrate pests attacks
[119]. Heinrich et al. [116] reported that several medicinal plants which
contain alkaloids have been used by the early man as pain relievers and
as recreational purposes or in some religious ceremonies to achieve a
psychological state in which they could communicate with their ancestors
or god. Structure of reserpine is given in fig 3 as an example of alkaloids.
Reserpine was derived from Vinca rosea and Rauwolfia serpentine and it
reduces the production of neurotransmitters which causes hypotension and
sedation by interfering membrane of synaptic vesicles [121].

Fig 3. Structure of reserpine (an alkaloid) (Adopted from: [45]

iii). Phenolics
Another class of plant secondary metabolites are phenolics which are
characterized by the presence of one or more hydroxyl (-OH) groups
attached to an aromatic ring either benzene or some other complex
aromatic ring structure [116]. Phenolics plant secondary metabolites on the
basis of their structure can be classified into two broad classes, flavonoid
and non-flavonoids phenolic compounds and they are responsible for the
development of different colors in plants and play a role in pollination
also they protect plants from UV radiation and pathogens [116,119]. A
three ring structure with two aromatic centers (ring A and B) and a central
oxygenated heterocyclic ring (C) are contained by flavonoids which are a
large and complex group of phenolics compounds [122] (Fig 4). Flavonoids
are known to be present in garlic and they have been found effective in
reducing atherosclerosis, coronary thrombosis, cholesterol level and many
other serious as well as fatal ailments [121].

Cite this article as: Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil. Bioactive Compounds from Medicinal Plants and Their
Importance in Drug Discovery in Pakistan / Mat. Sc. Pharm 1(1) (2017) 17-26
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Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil/ Matrix Science Pharma 1(1) (2017) 17–26

Fig 6. Structure of aloesin (a glycoside) (Adopted from: [129])

10. Bioactive compounds and defense mechanisms in plants

Bioactive compounds (also known as defense bioactive compounds) are a
wide variety of chemically diverse compounds produced by plants through
complex mechanisms to respond the attacks of insect herbivores and
microbial pathogens. Bioactive compounds from plants have been widely
used in cosmetic, food and pharmaceutical industries [130]. Microorganisms
are causing diseases in a huge number of plant hosts and are responsible for
big losses in economical crops and also preventing valuable food distribution
worldwide [131-132]. The plants which are continuously exposed to a large
number of pathogens are being attacked in both chemical and mechanical
ways by these pathogens [133]. It has also been found that against these
Fig 4. Basic structure of flavonoids (Adopted from: [123]) pathogen attacks, plants show both inducible and constitutive defenses
[134]. And these defenses are due to the transcriptional regulation of genes
On the other hand simple phenols (e.g. euginol, hydroquinone, catechol, which plays a primary role in response against the pathogen infections in
phloroglucinol and p-anisaldehyde) [124], the C6-C3 phenyl propanoids plants [135]. The pathogen attacks induce a number of defense-related and
and their derivatives (caffeic acid, cinnamic acid, ferulic acid myristicin pathogenesis related (PR) genes in plants and these genes are regulated
and synapyl alcohol), the C6-C1 benzoic acids (gallic acid, vannilic acid transciptionally through different signal transduction pathways which
and protocatechic acid), coumarins (warfarin, scopoletin and dicoumarol), are mediated by ethylene [136], salicylic acid [137], jasmonic acid [138]
hydrozable tannis (gallotannins and ellagitannins) and lignans and related and probably hydrogen peroxide [139]. A wide range of mechanisms are
compounds all are included in non-flavonoid phenolic compounds. involved in plants for defense against invading pathogens. These include the
induction of those genes which encode pathogenesis-related (PR) proteins,
iv). Terpenoids the hypersensitive response (HR) which is necessary for restricting the
The largest group of plant secondary metabolites is terpenoids which are pathogens from spreading at the primary site of infection and the production
also known as isoprenoids [119]. Terpenoids are classified on the basis of of those enzymes which are involved in the production of phytoalexins. In
isoprene units into monoterpenes (C10), sesquiterpenes (C15), diterpenes addition, those which are related to tissue repair, oxidative stress protection
(C20), triterpenes (C30) and tetraterpenes (C40) [46,116]. They play and cell wall lignification [140].
different roles in plants such as in defense, thermotolerance, wound scaling
and pollination of seed crops. Terpenoids also give flavors to fruits, fragrance Different active protective mechanisms and constitutive defense barriers
to flowers and also responsible for the quality of agricultural products which are accompanied by a variety of physical and biochemical changes
[116]. Structure of bisabolol is given in fig 5 representing Sesquiterpenes are also involved in plants to play an important role in defense against
(C15). Bisabolol is used as an anti-bacterial, antifungal, antimalarial and different pathogens. Synthesis of a group of pathogenesis-related (PR)
mulluscicidal drug [125] and isolated from different plant sources such as proteins which are host-encoded proteins is one of the most studied defense
Salvia stenophylla [126] and Plinia cerrocampanensis [127]. responses in plants. It has been suggested recently that thionins [141], plant
defensins [142] and lipid transfer proteins [143] which are different groups
of small, basic and cysteine-rich antimicrobial proteins they may play an
important role in plant defense responses. In fact it has been found that
some PR proteins have in vitro antifungal activity [144]. Similarly, Alexander
et al. [145] has also reported that the genetically engineered and over-
expressing PR proteins in plants have been found to be resistant against
pathogen infections. Moreover, by the treatment of abiotic elicitors the PR
proteins can also be induced in plant tissues. In addition to biotic elicitors,
polyacrylic acid, benzoic acid, ethephon, 2,6-dichloroisonicotinic acid (INA),
salicylic acid (SA), benzo (1,2,3) thiadiazole-7-carbothioic S-methyl ester
(BTH) and DL-β-amino-n-butyric acid (BABA) are also some renowned
chemical inducers of PR proteins [145].

i). Antimicrobial peptides (AMPs)

Fig 5. Structure of bisabolol (Adopted from: [125]) Antimicrobial peptides (AMPs) provide resistance to plants against
microbial infections and have been detected in many agricultural plant
v). Glycosides species [146]. In vitro strong antimicrobial activity of antimicrobial peptides
Glycosides are plant secondary metabolites which are made up of two and their localization in a wide range of plant tissues have indicated
components including glycone (a carbohydrate component) and aglycone that they can play an important role for the protection of plants against
(a non-carbohydrate component). The former component usually consists pathogens. The role of these AMPs in plant protection is also supported by
of one or more glucose units and the latter component may be any one of their high expression levels both systemically and locally during the attacks
the plant secondary metabolites from alkaloids, phenolics or terpenoids of different pathogens [147].
[46,116]. Anthraquinone glycosides, steroidal (cardiac) glycosides and All these AMPs do have antimicrobial activity and they can be categorized
coumarin glycosides are medically important glycosides but the medicinal into different types according to their structures and functions [146].
importance is not limited to these glycosides only. Structure of aloesin is In different plants two well-known subclasses of these AMPs are found
shown in fig 6 that is an example of glycoside. Aloesin has been isolated which are called as thionins and plant defensins [148]. Chitin-binding
from Aloe vera and reported for antioxidant activity, free radical scavenging proteins [146], knottin-type peptides [149] and protease inhibitors [150]
and anti-inflammatory effects [128]. are some other AMPs which have also been isolated from medicinal plants
and studied. Much attention has been given in recent years to the potential
use of AMPs to design novel fungicides which should be environmentally
friendly. To engineer genes of disease resistance in plants which can reduce
the use of additional chemical fungicides, AMPs are also a possible source
of these genes [151].

ii). Anticancerous compounds

Over the last century, the secondary metabolites of plants and their
derivatives have acquired most new clinical applications as they are being
applied to fight against cancers [16]. Drug discovery from medicinal plants
for the treatment of different cancers has played a vital role. In a study [51]
it was shown that from all the available anticancer drugs, , there were 40%
natural products or their derivatives with another 8% were considered as a
mimic of natural products. Many bioactive compounds comprising

Cite this article as: Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil. Bioactive Compounds from Medicinal Plants and Their
Importance in Drug Discovery in Pakistan / Mat. Sc. Pharm 1(1) (2017) 17-26
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Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil/ Matrix Science Pharma 1(1) (2017) 17–26

anticancerous activity have also been extracted and purified. The extracts Nadu, India. BMC Complement. Altern. Med. 6: 35–41.
of Pavetta crassipes showed potential toxicity against human cancer cells [3] Bolzani, V. da S., M. Valli, M. Pivatto, C. Viegas. 2012. Natural products
[152]. The leaves of Pavetta crassipes have also been reported to have from Brazilian biodiversity as a source of new models for medicinal
indolomonoterpenic alkaloids, hydroxyl-elaeocarpidin and elaeocarpidin chemistry. Pure Appl. Chem. 84: 1837–1846.
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Catharanthus roseus (L.) and Vinca rosea (L.) two anticancerous agents medicines. Vet. World. 1(11): 347-350.
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Importance in Drug Discovery in Pakistan / Mat. Sc. Pharm 1(1) (2017) 17-26
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Cite this article as: Ghulam Mustafa, Rawaba Arif, Asia Atta, Sumaira Sharif and Amer Jamil. Bioactive Compounds from Medicinal Plants and Their
Importance in Drug Discovery in Pakistan / Mat. Sc. Pharm 1(1) (2017) 17-26