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Preface
from natural resources are no longer preferred alternative, as it was fifty years ago, boosting the effectiveness of naturally bioactive substances with nanoparticles has become a prevalent characteristic.
Chapter 24 discuss the bioactive compounds as well as the mechanisms of active substance release
and drug delivery routes. Drugs with low bioavailability (e.g., hydrophilic therapeutics) are often administered by injection. Bioactive compounds of plant origin are used all over the world because of their
positive impact on human and animal health and because of their beneficial, specific properties. The
most popular bioactive compounds beneficial to health have been identified and defined earlier, others
are yet to be discovered. In particular, the most common biological activities of these compounds were
indicated, such as: antiallergic, antidepressant, antidiabetic, anti-inflammatory, antimicrobial, antitumor,
antiviral, antithyroid, anxiolytic, to cardioprotective, hepatoprotective and flatulence inhibiting effects.
The beneficial properties of bioactive compounds may be associated with substances like alcohols,
terpenoids, phenolic antioxidants and rosmarinic acid, which are present in several medicinal plants.
Chapter 25 give an overview of the essential aspects of bioavailability and bio accessibility of phytochemicals, components restricting the oral bioavailability of the phytonutrients and the mechanisms
responsible for the absorption and metabolism of bioactive compounds. The chapter will also discuss
some of the recent delivery systems that can be accessed to improve the bioavailability of bioactive
compounds by several folds. Phytochemicals or phytonutrients, are chemicals produced naturally by
plants for protection and prevention from diseases. Bioactive compounds are found in fruits, vegetables,
whole grains etc. including a heterogeneous class of compounds (polyphenolic compounds, organosulfates, tocopherols, carotenoids, and phytosterols) ranging between a wide range of chemical structures
(lipophilic or hydrophilic), natural diversity (ubiquitous or specific), possible action site, concentration
range both in human body and food matrix, efficiency against oxidative damage, biological activity, and
specificity. Various aspects like sources, biomolecules present in the food and chemical interactions with
other phytochemicals interfere with the bioavailability of these bioactive compounds. Several other factors
drastically affecting the oral bioavailability of phytochemicals include controlled discharge of bioactive
components from food matrix, their solubility in gastric juice, absorption through intestinal epithelial
cells, and chemical or enzymatic reactions taking place in the digestive system. Studies on potent health
benefits of phytochemicals and methods to enhance their bioavailability are still much in inception.
As a comprehensive collection on the latest findings related to biomedical sciences, computational
biology and bioinformatics, botany, Herbal drug discovery, microbial diseases and their herbal management, essential oils based-herbal therapeutic drugs, pharmacological uses of medicinal plants and
natural bioactive compounds etc. “Advanced Phytochemicals and Plant-based Drug Discovery”, provides
students, academicians, practitioners, and researchers with a complete understanding of the development
of applications and concepts surrounding these critical issues.
Ajeet Singh
ICAR-Indian Institute of Wheat and Barley Research, India
xxx
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xxxi
Acknowledgment
The editor would like to thank the people involved in this project for their quality time, expertise, and
countless effort. The editor is extremely indebted to the contributors/authors for the countless time and
expertise that they have put into their texts. The editor is also very thankful reviewers for their constructive
reviews in improving the quality and presentation of the contents. Furthermore, the editorial advisory
board for their prodigious supports and suggestions. The teachers, colleagues, friends, and well-wishers
for their endless inspiration and assists.
I would like to express the heartiest gratitude to almighty God and parents. I extremely grateful to my
father Shri Omprakash Singh and mother Late Smt. Shyamwati Devi, brothers and sisters and beloved
wife Dr. Shivangi for their blessings, endless support and encouragement. Further, it is an honor to
acknowledge, mostly I learned and influenced by Prof. R.S. Mehrotra, Dr. Navneet Bithel, Dr. M.U.
Charaya, Dr. K.R. Aneja, Dr. Ashok Agrawal, Dr. D.K. Maheshwari, Dr. Ram Lakhan Singh, (Vice
chancellor), Nilamber Pitamber University, Medininagar, Palamau, Jharkhand), Dr. Praveen Trivedi
(Vice Chancellor, Jai Narayan Vyas University, Jodhpur, Rajasthan), Dr. A.P. Garg (Vice chancellor,
Shobhit Institute of Engineering and Technology, Meerut), Dr. Inderjeet Singh, (Vice chancellor, Guru
Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab), Dr. R.C. Dubey, Dr. Premlal
Uniyal, Dr. Sewa Ram, Dr. Devendra Singh Malik, Dr. Sneh Narwal, Dr. O.P. Gupta, Dr. Vanita Pandey,
Dr. Bikarma Singh, Dr. P.K. Sharma, Dr. S.K. Shahi, Dr. Dinesh Chand Sharma, P.V. Tiwari, Dr. Ajay
Prakash, Dr. H.V. Raghu, Dr. Neelofar Khan and Dr. Praveen Sharma, Dr. Prabhat Kumar, for their
valuable suggestions and guidance.
My special thanks to Dr. Manmohan Singh Chauhan (Director, ICAR-National Dairy Research Institute
Karnal Haryana, India), and Dr. G.P. Singh (Director, ICAR-Indian Institute of Wheat Research, Karnal,
Haryana, India).
I am also thankful to my friends Dr. Padam Singh, Dr. Brijesh Kumar, Dr. Nikhil Mehta, Dr. Ankita
Gautam, Dr. Shruti Sharma, Dr. Harvijay Singh, for their endless support.
My special thanks to Prof. R.S. Mehrotra and Dr. M.U. Charaya, who inspired me and develop writing
skills and taught to me to never compromise with the quality.
Last, but definitely not least, I am especially thankful to IGI Global publisher, USA for giving me a great
opportunity to publish this book and Elizabeth Barrantes, Assistant Development Editor IGI Global their
aid in the preparation in this edition.
Ajeet Singh
ICAR-Indian Institute of Wheat and Barley Research, India
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Section 1
Phytochemicals in Disease
Management and Herbal Drug
Discovery
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Chapter 1
Therapeutic Utilization
of Bioactive Compounds
and Phytochemicals:
A Current Scenario and Future Prospective
Himani Sharma
Chaudhary Charan Singh University, India
1
Aashaq Hussain Bhat
Institute of Biology, University of Neuchatel, Switzerland
Ashok Kumar Chaubey
Chaudhary Charan Singh University, India
ABSTRACT
Bioactive compounds are compounds that are naturally extracted from plants and microbes. They are
designated as energy-dense molecules because they play an important role in the normal functions and
metabolic pathways of life. Not all bioactive compounds have positive impacts on pathways, and some
have negative consequences as well. It has been observed that these derived bioactive compounds possess remarkable characteristics such as healing, anti-cancerous, anti-oxidant, etc. Phytochemicals are
the bioactive compounds that are present in foods and possess the ability to interfere positively with the
metabolism of human health. They have been classified as alkaloids, terpenoids, phytosteroides, resveratrol, and cardiac glycosides. It has been observed that these bioactive compounds are the center of
attraction in the drug discovery areas which are utilized against various diseases as plants and microbes
are exploited for the extraction of bioactive compounds.
INTRODUCTION
Bioactive compounds are compounds that are naturally extracted from plants and microbes. The term
DOI: 10.4018/978-1-6684-5129-8.ch001
Copyright © 2022, IGI Global. Copying or distributing in print or electronic forms without written permission of IGI Global is prohibited.
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Therapeutic Utilization of Bioactive Compounds and Phytochemicals
‘bioactive’ comprises two words i.e., ‘bios’ and ‘activus’ which refer to compounds having the ability to
provide energy to humans. They are designated as energy-dense molecules because they play an important
role in the normal functions and metabolic pathways of life. Not all bioactive compounds have positive
impacts on pathways, and some have negative consequences as well. Besides this, several bioactive
compounds have both positive and negative effects on the metabolic pathway. The positive and negative
effects of bioactive compounds are determined by their in the body. Though, their concentration is also
dependent on so many factors such as the nature of the compound, components of compounds, their
interaction with the other molecules or substances, etc. It has been observed that these derived bioactive
compounds possess remarkable characteristics such as healing, anti-cancerous, anti-aging, antipyretic,
etc. (Huang et al., 2010; Bendary et al., 2013; Nath et al., 2013). There are some essential bioactive
molecules which have been required by the body in order to develop resistance against various disorders
(Biesalski et al., 2009). There are some non-essential bioactive molecules whose presence increases the
metabolism but their absence doesn’t have any consequences (Biesalski et al., 2013). The essential bio-
active molecules comprises of vitamins, fatty acids which plays important role in metabolic pathways.
Some of the vitamins are required by the enzymes as cofactors. Though they are considered beneficial
for human health, still, consumption of these compounds beyond the prescribed doses can cause adverse
effects also (Chambial et al., 2013). Phytochemicals are the bioactive compounds that are present in
foods and possess the ability to interfere positively with the metabolism of human health. They are the
non-essential compound which shows diversity in structure and function (Biesalski et al., 2009). They
have been classified as alkaloids, terpenoids, phytosteroides, and cardiac glycosides (Somani et al., 2015).
It has been observed that these bioactive compounds are the center of attraction in the drug discovery
areas which are utilized against various diseases as plants and microbes are exploited for the extraction
of bioactive compounds. Phytochemicals are the ones which are mostly present as active compound or
secondary metabolite in the plants. There are primary and secondary metabolites in the plants. Primary
metabolites are those compounds which are required by the plants for their survival purposes (Akhtar et
al., 2019; Omeroglu et al., 2019). On the contrary, secondary metabolites are the ones which have been
used by the plants for their defense purposes (Zhang et al., 2015; Cooper & Nicola, 2015).
MAJOR PHYTOCHEMICALS
Alkaloids
These are one of the classes of secondary metabolites processed by the plants. The basic structure of
alkaloids comprises of the nitrogen group. The presence of nitrogen group in the place of hydrogen
characterizes it under alkaloids. They possess the antimicrobial and anti-analgesic effects. The antimicrobial activity of these compounds came into light when it has been observed that they enhance
the activities of WBCs (White Blood Cells). Due to the enhance activity of the WBCs, microorganism
clearance increases in the cell (Ogunwenmo et al., 2007). The other alkaloids found to be complex in
structure which involves the aromatic alkaloids. They target the genetic material of the organisms and
like ethidium bromide; they are also involved in the intercalation along with the cell wall (Cowan, 1999).
The most commonly used alkaloids have multifaceted role in the medicine field. They are known to act
as antimalarial, anti- depressant, anti antineoplatic activities and many more (Ngoci et al., 2011). The
utilization of the alkaloids is not limited to these activities only. Besides this, they are involved in the
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Therapeutic Utilization of Bioactive Compounds and Phytochemicals
treatment of various diseases. They have the potential to stimulate various known and important neurotransmitters at the junction where a muscle and neuron passes down the signal with the help of these
neurotransmitters (Ngoci, et al., 2011). They are also helpful in reducing the pain cycles which frequently
arouses in different conditions such as wounds, pain in the abdomen etc. (Ngoci et al., 2011). Cancer is
one of the diseases where metastases become a major problem in the malignant tumor. There are various
drugs and chemicals have been exploited in the chemotherapy to restrict the growth of the tumor. The
alkaloids also play important role in the treatment of cancer mainly leukemia and Hodgkin’s disease. As
mentioned earlier, the dose of the phytochemicals is very crucial in deciding the adverse and beneficial
effects. Though, they are very useful for the metabolic activities and other properties which provide
benefits to human society. It has been seen that some of the alkaloids are not good for the metabolic
purposes and they possess negative effects on the health (Ogunwenmo et al., 2007; Ngoci et al., 2011).
Tannins
One of the classes of polyphenols is tannins. The basic structure of tannins consists of the phenolic ring
and they are classified into two categories i.e., hydrolysable and condensed. The hydrolysable tannins
have been obtained by the action of gallic acid on the tannins. The –OH group present on the tannins
undergo esterification process by the gallic acid (Al Mamari, 2021). On the contrary, the tannins which
don’t undergo hydrolysis reactions are termed as condensed tannins. As their name suggests they are
formed from the condensation reactions (H. Al Mamari, 2021). The major difference between the two
categories which leads to the classification is that hydrolysable tannins can be easily degraded by the
action of acids as they can be hydrolyzed. However, the condensed tannins doesn’t degraded that easily
as they can’t be hydrolyzed by the acids. The condensed tannins possessed the antioxidant activities and
found to be involved in many other reactions such as restricting the oxidative enzymes and many more
(Navarro et al., 2003; Vit et al., 2008; Ngoci et al., 2011). Various studies also suggest the role of tannins
in inhibiting the growth of tumor. They target the cell death pathway commonly known as apoptosis.
In cancer cells, it has been observed that all the factors and enzymes responsible for natural cell death
found to be down regulated which helps growing tumor. Tannins work towards the stimulation and
enhancement of the apoptosis, so that tumor growth can be reduced or inhibited (Scalbert et al., 2005).
Tannins also functions as anti- microbial agent. The microorganisms in order to develop infection
require attachment with the host which in turn needs adhesion proteins. These adhesion proteins have
been targeted by the tannins and sometimes, they also disrupt the membrane which leads to either prevention from the infection or death of the microorganism (Cowan, 1999; Okuda, 2005; Biradar et al.,
2007; Ngoci et al., 2011). To inhibit the microbe’s infection, they extend their functions beyond the
disruption of cell wall or cell wall proteins. It has been seen that tannins gather those metal ions which
are requisite for the development of microbes. As some of the factors required for the attachment, some
of them necessarily work on the growth and many more. Reverse transcriptase is the enzyme which is
utilized by the viruses especially retroviruses for integrating its genetic material into the host genome.
The enzyme catalyzes the reverse transcription reaction where DNA has been obtained from the mRNA.
This enzyme is also targeted by the tannins which restricts its activity (Okuda, 2005; Biradar et al., 2007;
Ogunwenmo et al., 2007; Ngoci et al., 2011). It is been interesting to know that the susceptibility of the
microorganism towards the tannins infection increases with the increment in the number of –OH group
(Przybylski et al., 1998; Cowan, 1999; Biradar et al., 2007; Samy & Gopalakrishnakone, 2008; Ngoci
et al., 2011). Hormones play major role in the growth and development of the body and they can travel
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Therapeutic Utilization of Bioactive Compounds and Phytochemicals
distant sites as they are released from the ductless glands. They also play important in signaling. Tannins,
despite of all toxic effects to the microbes, also act in this system where they target the receptors of the
estrogen. They are found to be lethal to many mollusks, as a result of which they are highly exploited in
the controlling the infection of the Schistosomiasis. This infection is caused by the trematode parasite
known as Schistosoma spp. and its life cycle involves the definitive and intermediate hosts as humans
and mollusks, respectively. They are also used in curing the diarrhea, fungus and parasitic infections
along with arterial clearance (Awoyinka et al., 2007; Ogunwenmo et al., 2007; Ngoci, et al., 2011).
Flavonoids
The basic structure of flavonoids comprises of 15 carbons forming a C6-C3-C6 compounds. The carbons are attached to the benzene rings and other flavonoids structure derived from the modification in
the basic structure. The presence of the sugar moieties increases the solubility of these compounds in
water (Harborne, 1973). Like all other secondary metabolites, they are helpful in reducing the oxidative
stress. The oxidative stress also produced from the Low-density lipoprotein. The increasing amount of
bad cholesterol also found to be harmful for the heart. The metabolic processes carried out to decrease
the oxidative stress seem to be favored in the presence of flavonoids especially the quercetin (Ngoci, et
al., 2011). They play an important role in the elimination of those compounds which possess the capability of inducing mutation or cancer. Both are serious for the body as mutations are one of the factors
in developing cancer (Ogunwenmo et al., 2007; Ngoci et al., 2011). These compounds also restrict the
growth of the microorganism. They inhibit the growth either by inhibiting the protein required for the
attachment to the host or by interfering with their membrane (Navarro et al., 2003; Al-Bayati & AlMola, 2008; Samy & Gopalakrishnakone, 2008; Kaur & Arora, 2009; Ngoci et al., 2011).Most of the
drugs derived from this have been recommended to the patients of blood pressure as it lowers the pressure and decrease the muscles heavy utilization of the oxygen (Dong et al., 2005; Ngoci et al., 2011).
The consumption of these bioactive molecules has been extended where allergies, spasms and other
diseases such as asthma also treated (Ngoci, et al., 2011). Though, most of the flavonoids derivatives
have the potential to restrict the growth of various disease caused by the microorganism, still, it has been
observed that presence of the alcohol group in the structure increases the efficacy of flavonoids derivatives against the microorganism in comparison to those which lacks the group (Cowan, 1999; Samy &
Gopalakrishnakone, 2008; Ngoci et al., 2011).
Saponins
They are present in the leguminous plants. The name saponin derived from the characteristics of the
compounds which have the ability to make foams when come in contact with an aqueous solution like
soap. The other noticeable characteristic of saponin is the damage to blood cells which gets hemolysed
in the presence of these compounds (Harborne, 1973).Their characteristics have been exploited in
treating the cough as they induce the release of the sputum through the natural openings such as nose
and mouth. Like all other bioactive molecules, they are also possess the ability to restrict the growth of
microorganism especially protozoa. The protozoan consists of the cholesterol molecules which are the
targets of saponins. Every biological membrane requires cholesterol but this has been disrupted by the
saponins which becomes fatal for the protozoa. The adjuvants play an important role in promoting the
immune response. The role of saponins as adjuvants becomes useful in the vaccines (Ngoci et al., 2011).
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Therapeutic Utilization of Bioactive Compounds and Phytochemicals
They inhibit the growth of the bacteria by utilizing their properties in which they lyse the membranes of
the bacteria. Besides this, the reaction in the extracellular medium increases which makes the bacteria
more susceptible for killing. This is also occurred due to the saponin property of reducing surface tension (Al-Bayati & Al-Mola, 2008).
The drugs derived from the saponin also inhibit the cancer cells invasiveness. The normal cells didn’t
harm from this drugs as they target cholesterol of cancer cells membrane. The reaction leads to the induction of various checkpoints which promotes the arrest and promotes the cell death (Ngoci et al., 2011).
It has been seen that the bacteria responsible for the colon cancer has been inhibited by the saponins
(Ngoci, et al., 2011). It has been found that saponin also possesses the ability to reduce to blood pressure which prevents most of the heart problems. Likewise, it has been observed that in the presence of
saponins, there is a decrement in the demand of oxygen by the myocardial muscles (Dong et al., 2005).
Phytosteroids
This is one of the hormones or bioactive molecules which shares similarity with the animal hormones.
The basic structural similarity between the two has been observed with the contrasting side groups which
them different from each other (Ngoci et al., 2011). Due to their structural similarities with the animal
hormones, they have been used in the pregnant women for the comfortable delivery without complications. Furthermore, they are prescribed to women for increasing the fecundity. They also exploited for
increasing the sex drive in males. Various artificial sex hormones could be prepared from this due to
the structural similarity. They are mostly prescribed at the time of contraception (Edeoga et al., 2005;
Ngoci et al., 2011). The uses of these steroids didn’t stop here as they are exploited for treating diseases
caused by microorganism, inflammation and extending their properties to cure stomach related problems.
They have been reported for reducing the levels of the bad cholesterol which is harmful for the heart
(Ngoci et al., 2011). They inhibit or suppress the immune responses which in some patients have been
exaggerated leads to various problems. The drug derived from the phytosteroids is physalins utilized to
treat those immune responses (Soares et al., 2005; Ngoci et al., 2011).
Terpenoids
Isoprene unit has been derived from the Isopentenyl diphosphate (IPP) and terpenoids derived from the
isoprene. They share similar basic structure with differences in the adjoining groups (Harborne, 1973).
They have been used for treating the diseases caused by the fungus, virus, bacteria and protozoa. They,
in contrast to phytosteroids, have known to boost the immune systems of the humans. The action of these
compounds on cancer cells is commendable as they restrict the invasion without harming the normal
body cells (Roberts, 2007; Ngoci et al., 2011).Their uses doesn’t end here, but, the invasion of the micro-
organisms also limited by them. It has been evident from the studies that they target the membranes of
these microorganisms which are the base of attachment (Cowan, 1999; Ogunwenmo et al., 2007; Samy
& Gopalakrishnakone, 2008; Ngoci et al., 2011). Furthermore, if membranes have been disturbed then
the composition and permeability also gets affected. Sometimes, they are disturbed to that level where
the intracellular material comes out to exterior. The other possible reason came into existence suggested
that interaction between the phytochemicals and the interior materials of the cell serves as the bacterial
inhibitor sites (Trombetta et al., 2005). They are also used to treat epilepsy and other viral borne diseases along with curing the diseases of the lungs (Ngoci et al., 2011). The in vitro studies demonstrated
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Therapeutic Utilization of Bioactive Compounds and Phytochemicals
that the terpene derived from the Ginseng interacts with the master gland and hypothalamus along with
adrenal glands. This fact has been established by observing the levels of hormones in the blood. The
axis which controls all the hormones has been targeting by the derivatives. There is a rise in adrenal
cortex hormone levels which have been regulated by the axis only (Briskin, 2000; Ngoci et al., 2011).
Cardiac Glycosides
These are the compounds which are not good for human health as they are poisonous and sometimes
show lethal effects. Though, they are harmful, still they are used as therapeutic agents for heart diseases
(Harborne, 1973). At the times of heart failure, the drugs derived from this has been utilized which interferes physiology of the heart. In congestive heart failure, it has been seen that the heart doesn’t able
to pump the blood properly as a result of which it builds up in the pulmonary area (Ogunwenmo et al.,
2007; Ngoci et al., 2011).
BIOACTIVE MOLECULES IN DIFFERENT PLANTS
AND THEIR THERAPEUTIC USE
There are various plant species which have been used as therapeutic agents. The Aescin bioactive molecule
has been derived from the plant Aesculus hippocastanum L. which is used to treat inflammatory diseases
(Sirtori, 2001). The other bioactive molecule of plant Allium sativum L. i.e., allicin used to lower the
lipid concentration in the body as well as also acts against the bacterial diseases (Jain et al., 1993). The
bioactive molecule androgropholide derived from the Androgrophis paniculata L. known to protect the
lever and used for curing liver related problems (Kapil et al., 1993). In the treatment of malaria, drugs
derived from the bioactive molecules artemesinin obtained from the plant Artemesia annua L. have been
used (Lin et al., 1987). The berberine molecule of Berberis vulgaris L. is used to treat bacterial diseases
and diarrhea (Amin et al., 1969). Rheumatoid arthritis drugs comprises of bioactive molecules boswellic
acid of Boswellia serrata L. (Safayhi et al., 1992; Taneja & Dhar, 1996). A Saikosaponin D molecule
(plant Bupleurum Chinese L.) is known to increase the efficiency of liver metabolism (Yen et al., 1991).
The capsaicin molecule of Capsicum annuum L. used as topical analgesic (Bernstein et al., 1987). The
emetine (Cephaelis ipecacuanha L.) molecules act as antiamebic in dysentery (Botero, 1978). Quinine
is the compound extracted from the Cinchona succirubra L. plant and the molecule exploited for treating
malaria (Leung, 1980). The serious diseases like Gout, Hepatitis and cancer found to be treated with the
bioactive molecule of plant Colchicum autumnale L. known as colchicines (Lange et al., 2001; Warnes,
1991). Curcumin molecule of Curcuma longa L. used to treat bacterial diseases as well as also works
against tumor (Nagabhushan & Bhide, 1992). The challenging conditions in which failure of the heart
has to be treated, the drug derived from the plant Digitalis orientalis L. molecule digoxin is used (Foss
and Benezra, 1980; Campbell & MacDonald, 2003). The severe effects of migraine have been treated
with drugs derived from ergotamine and this is also used at the time of child birth (Kreilgard, 1977).
To maintain the hemostasis of the body, hydrastine (Hydrastic Canadensis L.) is prescribed (Genest,
1969). Most of the pain killers consist of aspirin as one of the components and this is the bioactive
molecule of Salix alba L. (Kaul et al., 1999). One of the compound synthesize from Silybum marianum
L. i.e., silybin is utilized as a protective agent of the liver (Hobbs, 1992; Wellington and Jarvis, 2001).
Besides this, the other fascinating properties of this compound make it more consumable including its
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Therapeutic Utilization of Bioactive Compounds and Phytochemicals
Figure 1. Vitamin C
antioxidant properties. The warts which occur on the skin induced by the virus population can be treated
with podophyllotoxin (Podophyllum peltatum L.) molecules. It is also used to inhibit the uncontrollable
growth of cancerous cells (Jardine, 1980; Canel et al., 2000). Vinblastine is mostly used in chemotherapy
for controlling the growth of tumor cells. This molecule is extracted from the plant Vinca rosea L. (Van
der et al., 2004). Another molecule which is consumed by the diabetic patient is as sweet as sugar with-
out its harmful effects. This sweetener has been prepared from the natural active compound stevioside
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