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INTRODUCTION TO PHYTOCHEMISTRY

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CHAPTER 1

INTRODUCTION TO
PHYTOCHEMISTRY
CHUKWUEBUKA EGBUNA1,*, JONATHAN C. IFEMEJE1,
TOSKË L. KRYEZIU2, MINAKSHI MUKHERJEE3, HAMEED SHAH4,
G.M. NARASIMHA RAO5, LAURENCE JOHN FRANCIS J. GIDO6,
and HABIBU TIJJANI7
1
Department of Biochemistry, Chukwuemeka Odumegwu Ojukwu
University, Uli, Anambra State, Nigeria, Tel.: +2347039618485
2
Department of Clinical Pharmacy, University of Pristina, Pristina,
Kosovo
3
Department of Biological Sciences, The State University of New York
at Buffalo, Buffalo, New York, USA
4
CAS Key Laboratory for Biomedical Effects of Nanomaterials and
Nanosafety, National Center for Nanoscience and Technology,
University of Chinese Academy of Science, 100049 Beijing, China
5
Department of Botany, Andhra University, Visakhapatnam,
Andhra Pradesh 530003, India
6
Research Center of the College of Medicine, Davao Medical School
Foundation Inc., Davao City, Philippines
7
Natural Product Research Laboratory, Department of Biochemistry,
Bauchi State University, Gadau, Nigeria
*
Corresponding author. E-mail: egbuna.cg@coou.edu.ng;
egbunachukwuebuka@gmail.com; https://egbunac.com
ORCID: https://orcid.org/0000-0001-8382-0693

ABSTRACT

Phytochemistry is the study of the chemicals produced by plants, particularly

the secondary metabolites, synthesized as a measure for self-defense
4 Phytochemistry, Volume 1

against insects, pests, pathogens, herbivores, ultraviolet exposure and

environmental hazards. Phytochemistry takes into account the structural
compositions of these metabolites, the biosynthetic pathways, functions,
mechanisms of actions in the living systems as well as it’s medicinal,
industrial, and commercial applications. The proper understanding of
phytochemical is essential for drug discovery and for the development of
novel therapeutic agents against major diseases. This chapter introduces
phytochemistry, discusses the history of modern phytochemistry, the
relationship of phytochemistry with other sciences and the importance
of phytochemistry. It also provides information on the sources and
classification of phytochemicals, prospects for phytochemists, the
usefulness of computational phytochemistry, biostatistics and the advances
in phytochemical research.

1.1 INTRODUCTION

It will be recalled that in the food chain, plants are referred to as the producers
because they had the ability to trap energy from sunlight, harness and assemble
some basic units which they transform through some chemical process
into complex high energy-yielding compounds that are readily available
to organisms. Their generosity became overwhelmingly and practically
complex to comprehend at a glance. A field has to emerge – “phytochemistry.”
Phytochemistry is the study of chemicals produced by plants, particularly the
secondary metabolites. It takes into account their structural compositions,
the biosynthetic pathways, functions, and mechanisms of actions in the
living system. The study of phytochemicals has been instrumental in the
discovery of new plant natural products which are of commercial values
in various industries such as the traditional and complementary medicine
systems, pharmaceutical industries, nutraceuticals, and dietary supplement
industries. Not left out is the cosmeceuticals industries, clothing and textiles
industries, food, wine, and beverage industries, the military among others.
Owing to the consistent threat of microorganisms, environmental hazards
to public health, the significance of phytochemistry in the medical and
pharmaceutical industries for the quest for the discovery of new drugs has
overshadowed their essence in other industries.
Phytochemicals have been in existence since time immemorial and
are known to be responsible for the organoleptic properties (color, taste,
flavor, aroma, and odor) of plants, such as the smell of garlic, ginger,
and the deep purple color of blueberries. The ability of plants to exhibit
Introduction to Phytochemistry 5

curative potentials and the characteristic difference that exists within them
may also have awakened early interests for the knowledge about their
chemical compositions. In the plant kingdom, these variations are quite
glaring. One example is the Four O’Clocks plant (Mirabilis jalapa), called
the marvel-of-Peru, or beauty-of-the-night because of its ability to open in
mid-afternoon through the night and closes in the early morning. Mirabilis,
a Latin word meaning wonder, also radiates some pleasant fragrances
and exhibits flowers of different colors such as a white, red, pink, yellow,
and some two-toned blooms simultaneously on the same plant. This
phenomenal features in their biodiversity can be understood through the
study of some chemical networks and interactions within the plants and
its external environment. Plants are diverse and widely distributed from
lands, rocky hills, mountains to marine environments. There are over
400,000 species of plants in the world (Pitman and Jørgensen, 2002), out of
which only a small fraction of about 35,000–70,000 species of plants have
been screened for their medicinal use (Veeresham, 2012). The medicinal
potentials of phytochemicals are exhibited from the least primitive to higher
plants. According to Fabricant and Farnsworth (2001), about 80% of 122
plant-derived drugs are related to their original traditional uses. Reportedly,
as at the dawn of 21st century, 11% of the 252 drugs considered as basic
and essential by the World Health Organization (WHO) were exclusive of
flowering plant origin (Veeresham, 2012).
In the evolutionary study of phytochemicals, it was believed that there
was little free oxygen in the atmosphere when plants first evolved. The direct
consequence of this is that as plants metabolize, the oxygen concentration
in the world increased. This polluted the environment and to deal with
it, plants began to synthesize antioxidants molecules to protect it from
highly reactive species that are cytotoxic to the plant cells. Moreover, the
damaging effects of microbes on the cell structures of plants especially the
important biomolecules has left plants with no options than to synthesize
more bioactive compounds to protect it (see Chapter 3 for more details).
This evolutional theory is supported by recent evidence in the compositional
patterns of phytochemicals in plants. For instance, plant parts such as the
leaves, flowers, stems, barks, roots, and seeds that are prone to insects,
pests, microbial attacks, and the harsh environment have more amounts of
phytochemicals than other parts of the plants. Another supportive evidence
is the variation that exists in the same species of plants grown in the harsh
environment and those in areas with less environmental stress (see Volume
3, Chapter 12 and 13 for more information).
6 Phytochemistry, Volume 1

Prior to the in-depth understanding of phytochemicals, the first tool

employed by man is the “error and trial tools” which helped man to distin-
guish between edible and non-edible plants. Many casualties were recorded
at that time. Grazing animals are not left out, they graze, identify, and avoid
toxic plants through their sense of smell. The study continued and was
widely utilized by the oldest medical system, the Chinese and the Indian
Ayurvedic medicine, for the treatment of various diseases such as cancer,
cardiovascular diseases, and stroke. The knowledge became prominent in
the 19th and 20th century due to the extensive research using sophisticated
hybrid chromatography and spectroscopy for the extraction, isolation,
characterization, and purification of phytochemicals (see Chapter 8–14 for
detailed information).
This time around, research is ongoing and individual molecules are
constantly been discovered. The search for the discovery of new drugs and
repurposing of existing ones have driven the study of phytochemistry to
a new era employing in silico study techniques, applying simulation, and
molecular docking procedures of bioinformatics and cheminformatics.

1.2  BRIEF HISTORY OF MODERN PHYTOCHEMISTRY

The ethnobotanical studies of medicinal plants for the treatment of diseases

have existed since antiquity. For instance, the discovery of quinine marked
the first successful use of chemical compounds to treat infectious disease
(David and Jacoby, 2005). This was considered as the most important
medical discovery of the 17th century (Achan et al., 2011). But in practical
terms, the use of the quinine source, that is, the bark of the Cinchona
(quinaquina) tree dated back as at the 16th century. However, the beginning
of the isolation of plant chemical compounds marked the early stages of
modern phytochemistry. One such example is the isolation of alkaloids by the
brilliant pharmacist named Friedrich Wilhelm Adam Serturner (1783–1841)
in the latter part of 18th century (Krishnamurti and Rao, 2016). This isolation
not only led to the synthesis of new drugs but also to the purification of plant
extracts used as medicines. It is important to note that apart from being the
first to isolate an alkaloid, morphine, Friedrich Wilhelm was the first person
to isolate an active ingredient associated with a medicinal plant or herb. Not
long enough, his discoveries transformed pharmaceutical chemistry from a
state of alchemy to an acknowledged branch of science (Krishnamurti and
Rao, 2016).
Introduction to Phytochemistry 7

Under similar circumstance, the scientists Pierre Joseph Pelletier

and Joseph Caventou in 1820 isolated quinine from the herb Cinchona
officinalis, a unique drug with the indication to be used against malaria
(Dobson, 2001). Since then (within the last 300 years), many other
compounds have been successfully isolated and characterized such as
digitalis (1785), picrotoxin (1812–1884), curare (1856–1958), and salicin
(1860–1877) (Dikshit, 2017). With the progress in biotechnology during the
1970’s, a trend in the synthesis of various derivatives of plant metabolites
by mimicking the biosynthetic pathways has led to the production of more
stable, consequently, more effective albeit less poisonous compounds which
are of commercial value. The in vitro synthesis of phytochemical is detailed
in Volume 3 of this book.
Because terpenes represent a diverse nonetheless a problematic class for
extraction, the scientists Croteau and Cane in the 1980’s became the first to
determine terpene-synthesizing enzyme, called terpene synthase which has
led to the discovery of alternative pathways for the synthesis of terpenoids,
monoterpenes, diterpene, and so forth (Hartmann, 2007). The year 1990
became a significant period for modern phytochemistry because of the
development of sophisticated techniques.

1.2.1  STRUCTURE–ACTIVITY RELATIONSHIP

A feature of numerous modern-day drug is that they resemble the natural

products from the structural point of view, hence, without the existence
of these compounds in nature, scientist would never be able to treat the
countless number of diseases. A typical illustration is morphine, a model
substance of several anesthetics and salicylic acid, a model for the creation
of acetylsalicylic acid (Lydon and Duke, 1989). Another supporting evidence
of the stereochemistry of drugs (structural resemblance) which resulted in
problems is thalidomide (an analog of glutethimide, a sedative), a sleeping
substance administered to pregnant women with little-known aftermath
effects. During that period, numerous children born from pregnant mothers
who were administered it suffered phocomelia. This led the company to
suffer legal issues and has to withdraw the product from the market. In
reality, thalidomide contained a racemic mixture of both isomers, ((−) (S)
and (+) (R) thalidomide), whereas the isomer (−) (S) thalidomide had tera-
togenic effects, the other (+) (R) thalidomide doesn’t. Eventually, this drug
has found usage in cancer therapy (Fabro and Smith, 1967).
8 Phytochemistry, Volume 1

1.2.2  TRENDS

During the first decade of the 21st century, there was a decrease in the
interest of advancing the knowledge of plant-based chemistry by scientists
and pharmaceutical companies for greater interest in synthetic drugs because
they were easily mass-produced compared to the natural ones (Schmidt and
Ribnicky, 2008). However, due to reported side effects in patients, numerous
products were withdrawn from the market. A study has shown that the effect
of natural remedies persist higher for patients receiving treatment for their
long-lasting diseases. In view of this, there appears to be an increased usage
of plant products since 2010, which provides slower effects yet with fewer
side effects than synthetic medications. At present, new versions of the
pharmacopoeia are also adding recent knowledge about phytochemicals to
their volumes as well as gaining extended sophisticated products related to
the modification of plant enzymes to easily obtain therapeutic substances.
Worthy of note is that some remarkable phytochemicals have been discovered
from the marine environment. Marine-derived compounds have recently
gained a considerable interest because of the wide variety of pharmacological
applications. A detailed overview of marine phytochemistry can be found in
Volume 3 of this book.

1.3  RELATIONSHIP WITH OTHER SCIENCES

Phytochemistry is an important part of a number of disciplines. There have

been controversies and speculations as to the place of phytochemistry in
science. Some scientists consider it as a subfield of botany and chemistry while
others believed it should be part of the food and medicinal chemistry because
of its wide application in drug discovery. Categorically, phytochemistry is a
fulcrum and an aspect of many biosciences and would be difficult to single
out as a stand-alone science (Fig. 1.1). For instance, phytochemistry is an
important part of Systematic Botany, Taxonomy, Ethnobotany, Conservation
biology, Plant Genetic and metabolomics, Evolutionary Sciences and Plant
Pathology. The field of Pharmacy and Pharmacognosy, Complementary
and Alternative medicine, Ethnomedicine, Biochemistry, Microbiology,
Bioinformatics and Computational Chemistry employs the knowledge
of phytochemistry in the discovery of bioactive compounds. The field of
biotechnology and process engineering, nutrition and food sciences, organic
chemistry, employs the knowledge of phytochemistry in the production
of natural products with increase phytochemical yields. In the control of
Introduction to Phytochemistry 9

environmental pollution, the knowledge of phytochemistry is essential in

applying bioremediation techniques such as phytoremediation to mop up
harmful substances (detailed in Volume 3).

FIGURE 1.1  Some contributing fields to phytochemistry.

1.4  IMPORTANCE OF PHYTOCHEMISTRY

The knowledge of phytochemistry is essential in the:

1. Search for the discovery of new drugs and repurposing of existing

ones (see Chapter 20–25 for more information).
2. Characterization and standardization of traditional herbal drugs in
the crude form (see Chapter 9–15, 22 for a comprehensive informa-
tion on the various techniques involved).
3. Assessment of the toxicity levels of plants (see Chapter 16 and 17 for
details).
10 Phytochemistry, Volume 1

4. Understanding of plant physiology, biosynthetic pathways, and

metabolomics (detailed in Chapter 2, 3 and 8).
5. Identification and classification of plants (see Chapter 7 for more
information).
6. Study of inter and intraspecific chemical variability within plants
(see Chapter 3 for details).
7. Biotechnology and genetic engineering for the optimization and
synthesis of classic compounds (detailed in Volume 3).
8. Plant pathology (discussed in Chapter 3).
9. Development of environmentally friendly, biofungicides, insecti-
cides, pesticides, and herbicides (detailed in Volume 3).
10. Food preservations (see Volume 3 for more information).
11. Phytoremediation of toxic substances such as poisons and heavy
metals (presented in Volume 3).

1.5  PHYTOCHEMICALS, CLASSIFICATION, SOURCES, AND

FUNCTIONS

Phytochemicals are simply plant-derived chemicals. The word “phyto”

comes from the Greek word plant. It is used to refer to the secondary metab-
olites produced by plants. As noted earlier, these metabolites are usually
synthesized as a measure for self-defense against insects, pests, pathogens,
herbivores, ultraviolet exposure, and environmental hazards. Phytochemi-
cals differ from the essential nutrients (primary metabolites) such as the
carbohydrates, proteins, fats, minerals, and vitamins that are needed for
the day to day maintenance of the plants. Sometimes, phytochemicals are
used to refer to functional foods with antioxidant properties, nutraceuticals,
phytonutrients, anti-nutrients, phytotoxins, and so forth.

1.5.1  CLASSIFICATION OF PHYTOCHEMICALS

There are tens of thousands of phytochemicals. So far, there could not

have been a consistent classification system because of their numerous
number and the pace by which new phytochemicals are discovered. A simple
classification system divided phytochemicals into three chemically distinct
groups. They are the phenolics, terpenes, N, and S containing compounds
(Table 1.1).
Introduction to Phytochemistry 11

TABLE 1.1  Classification of Common Phytochemicals.

Major classes Subclasses Representatives
Phenolics Polyphenols Flavonoids, isoflavonoids, chalconoids,
lignans, stilbenoids (e.g., resveratrol),
curcuminoids, tannins (e.g., protocatechuic
and chlorogenic acids)
Aromatic acid Phenolic acids (e.g., gallic acid, tannic acid,
vanillin, ellagic acid), hydroxycinnamic acids
(e.g., coumarin)
Terpenes Monoterpenes (C10) Geraniol, limonene, pyrethroids, myrcene
Sesquiterpenes (C15) Costunolides
Diterpenes (C20) Abietic acid, cafestol, gibberellins
Triterpenes (C30) Azadirachtin, phytoecdysones
Polyterpenes (C5)n Tetraterpenes, for example, carotenoids,
rubber
Terpenoids Carotenoids β-carotene, lycopene, phytoene
(tetraterpenoids)
Xanthophylls Lutein, zeaxanthin
Triterpenoid Saponins, ursolic acid
Steroids Tocopherols (vitamin E), phytosterols
(β-sitosterol, campesterol)
N Alkaloids Nicotine, morphine, caffeine, theobromine,
(organonitrides) theophylline
Cyanogenic glucosides
Nonprotein amino acids Canavanine, azetidine-2-carboxylic acid
S Allicin, alliin, piperine
(organosulfides) Glutathione, phytoalexins
Others Phytic acid, oxalic acid, tartaric acid, malic acid, quinic acid

1.5.2  SOURCES OF PHYTOCHEMICALS

Phytochemicals are found in fruits, vegetables, whole grains, spices,

legumes, herbs, shrubs, and trees (Table 1.2). They get accumulated in plant
parts at different concentrations such as in the leaves, fruit, bark, stem, roots,
seeds, and flowers. Some phytochemicals are also synthesized by other
living organisms such as fungi, although the mechanism by which they
synthesize it might differ. However, many foods containing phytochemicals
12 Phytochemistry, Volume 1

are already part of our daily diet except for some refined foods such as sugar
or alcohol. The easiest way to get more phytochemicals is to eat varieties of
at least five to nine servings of fruits or vegetable per day representing colors
of rainbows. Chapter 6 of this book gave a holistic view of phytochemicals
acting as nutraceuticals.

1.5.3  FUNCTIONS OF PHYTOCHEMICALS IN THE LIVING

ORGANISMS

Phytochemicals perform quite a number of roles in the living organisms

(Table 1.2), and the mechanism by which they accomplish it has not been
fully understood. However, phytochemical functions as:

1. Antioxidants by preventing oxidative damage of important

biomolecules such as nucleic acids, proteins, and fats (elaborated
in Volume 2).
2. Antimicrobial agents: antibacterial, antifungal, antiviral, anti-trypano-
cidal agents (discussed in Volume 2).
3. Stimulation of immune system (see Chapter 5 for comprehensive
details).
4. Modulation of detoxifying enzymes.
5. Anti-inflammatory functions.
6. Reduction of platelet aggregations.
7. Physiological activities such as interfering with the binding of
pathogens to cell receptors.

Others include antimalarial activity, antidiarrheal, antihelminthic,

hepatoprotective, anti-atherosclerosis, anti-allergy, antidiabetic, antimuta-
genic, wound healing, pain relief, and antihypertension. Phytochemicals
are also used in the treatment of a sore throat, cough, toothache, ulcers,
menstrual bleeding, improvement of sperm count, dysentery treatment,
stomach upset, vertigo, and appetite enhancing. Many other functions of
phytochemicals exist depending on the plant. About 80% of the world
most useful drugs are from plants. Chapters 4 and 5 of this book gave an
overview of the biological functions and immunomodulatory properties
of phytochemicals. Volume 2 of this book contains many chapters that
discusses the various applications of plant natural products for the treat-
ment of diseases.
TABLE 1.2  Types of Phytochemicals, Sources, and its Biological Effects.
Phytochemicals Sources Biological effects References
Carotenes
α-carotene Carrots, sweet potatoes and winter Antimetastatic agent, provitamin A, immuno-en- Liu et al. (2015); Rodriguez-
squash, pumpkins, maize, tangerine hancement, cataracts, and macular degeneration Amaya (2015)
β-carotene Carrots, sweet potatoes and winter Coloring agent and as provitamin A, antimetastatic Avraham et al. (2017); Meh-
squash, dark, leafy greens, red, orange agent, immuno-enhancement, cataracts, and rad et al. (2018); Ravanfar
and yellow fruits, and vegetables macular degeneration, anti-autism agent et al. (2018)
Terpenes and Terpenoids
Triterpenoid Soybeans, beans, other legumes, maize, Anticancer agents, antidiabetic effect, anti-inflam- Grishko and Galaiko and
alfalfa matory agents, anti-oxidants, and so forth. (2016); Salvador et al.
(2017); Xu et al. (2018)
Diterpenes Mustard, bugleweeds, common skull- Antioxidant, antifeedant, antimicrobial, Faiella et al. (2014); Grishko
cap, germanders, and so forth anti-inflammatory and Galaiko (2016); De
Oliveira et al. (2017)
Monoterpenes Oils of citrus, cherries, spearmint, dill, Applications in drugs, flavors, and fragrances, Zebec et al. (2016); Mewalal
garlic, celery, maize, rosemary, ginger, advanced biofuels, enzyme inhibition, effects on bio et al. (2017); Zhang et al.
basil, citrus oils, caraway, mints channels (2017)
Steroids Almonds, cashews, peanuts, sesame Neuroactive, neuroprotective, and Chrbolka et al. (2017)
seeds, sunflower seeds, whole wheat, immunomodulatory increase muscle and bone
maize, soybeans, many vegetable oils, synthesis, regulate many aspects of metabolism and
avocado, rice bran, wheat germ, corn immune function, influence sex differences, and
oils, fennel, peanuts, soybeans, haw- support reproduction
thorn, basil, buckwheat
Astaxanthin Salmon, green algae, Krill, arctic Nutraceuticals, cosmetics, and the food and feed Rodriguez-Amaya (2015)
shrimp, red snapper industries, pigmentation, aquaculture, antioxidant,
and so forth.
Introduction to Phytochemistry 13
TABLE 1.2  (Continued) 14

Phytochemicals Sources Biological effects References

β-Cryptoxanthin Kamut, corn flour, quinoa, noodles, egg Provitamin A activity, antioxidant, reduces Rodriguez-Amaya (2015)
inflammatory disorders, effective against
rheumatoid arthritis, antimetastatic potential.
Lutein Colorful fruits and vegetables Reduced risk of age-related macular degeneration Olaf Sommerburg (1998);
and cataracts, found in macular pigment of human Rodriguez-Amaya (2015)
retina
Phenolic compounds
Natur al Parsley, celery leaf, rosemary, sage, Antimicrobial, antioxidant Gutiérrez-Larraínzar et al.
monophenols oregano, thyme, pepperwort, wild (2012)
bergamot
Polyphenols and others
Flavonoids Red, blue, purple pigments, tea, Antioxidant, antimicrobial, enzyme inhibition Ouédraogo et al. (2018); Xu
strawberries, gooseberries, cranberries, et al. (2018)
grapefruit, apples, peas, brassicas
(broccoli, kale, brussels sprouts,
cabbage), chives, spinach, endive, leek,
tomatoes
Isoflavonoids Soy, alfalfa sprouts, red clover, Antimycobacterial agents, estrogenic agents, wound Araya-Cloutier et al. (2017);
chickpeas, peanuts, kudzu, other healing agents, antimicrobial potential Coronado-Aceves et al.
legumes (2017); Ergene Oz et al.
(2018);
Aurones lemons, oranges, and grapefruit Active against hepatitis C, neuro-generatic agents, Liew et al. (2015); Boucherle
antifungal agents, antimicrobial, anticancer, et al. (2017); Liew et al.
antiviral, antimalarial, antioxidant, anti- (2017)
inflammatory, anticarcinogenic
Phytochemistry, Volume 1
TABLE 1.2  (Continued)
Phytochemicals Sources Biological effects References
Chalconoids Licorice root, citrus peel, apple peel Anticancer, antimalarial, antimicrobial, anti- Singh (2014); Mostofi et al.
inflammatory, anti-protozoal, anti-oxidant, (2015); Mirzaei et al. (2017)
antiproliferative agents, enzyme inhibition.
Flavonolignans Artichokes, milk thistle Antioxidant agents, antiviral agents, hepato- Althagafy et al. (2013);
protective agents, inhibiting blood coagulation Pyszkova et al. (2016); Bijak
et al. (2017);
Lignans Apricots, strawberries, Broccoli, kale, Cytotoxic against human tumor cell lines, Jiang et al. (2017); Sownd-
oats, wheat antioxidant, neuroprotective, cognition enhance- hararajan et al. (2017); Xu
ment, anti-inflammatory, enzyme inhibition et al. (2017);
Stilbenoids Grape (skins and seeds, grape wine), Cytotoxic against human tumor cell lines, Basheer et al. (2017); Cao
nuts, peanuts, Japanese knotweed root antioxidant, phytoalexins activity, anti- et al. (2016); Hu et al. (2018)
inflammatory activity, enzyme inhibition
Curcuminoids Turmeric, mustard. Anti-turmeric potential, anti-diabetic potential, drug Bahramsoltani et al., (2017);
interactive ability, painkiller, anti-microbial agents. De Meloa et al. (2017);
Verma et al. (2017)
Tannins Tea, berries, horse chestnut (Aesculus Enzyme inhibition and speed up agents, albumin Adamczyk et al. (2017);
hippocastanum), cranberry juice, peanut interactive agents, wound healing promoters, Barrett et al. (2018);
skin anti-microbial agents, Sekowski et al. (2018);
Aromatic acid Peppermint, licorice, peanut, wheat, Anti-oxidant agents, anticancerous effect, Cvijetic et al. (2018); Zhang
vanilla beans, cloves, soy antibacterial agents et al. (2018)
Glucosinolates Broccoli, cabbage, kale, cauliflower, Antioxidant, antitumeric effects, high doses cause Bieganska-Marecik et al.
turnip, mustard greens toxicity, lower doses stimulate appetite, (2017); Radošević et al.
heart-protective agent (2017)
Betalains Beets, chard, Amaranthus tricolor Antioxidant, anti-tumeric, anti-lipidemic, and Gengatharan et al. (2015);
antimicrobial activity Kumar et al. (2015)
Introduction to Phytochemistry 15
TABLE 1.2  (Continued) 16
Phytochemicals Sources Biological effects References
Chlorophylls Colorful fruits and vegetables. Antioxidant, photosensitizers, clastogenic activity, Dos Reis et al. (2015); Roca
wound healing, anti-inflammatory, photodynamic et al. (2016)
therapy
Amines Beetroot Cytotoxic nature, International Agency for Research Canales et al. (2017); Gu
on Cancer declared heterocyclic aromatic amines as et al. (2018); Papageorgiou
carcinogenic et al. (2018)
Carbohydrates Wheat, barley, rye, oat Source of energy, maintains cells, tissue, organ Arens (2018); Barazzoni
structures, some have role in maintaining stomach et al. (2017); Gerschenson
acidity, additives, role in insulin resistance, brain et al. (2017).
functions regulator
Phytochemistry, Volume 1
Introduction to Phytochemistry 17

1.5.4  ROLE OF PHYTOCHEMICALS IN PLANT DISEASE

MANAGEMENT

Plants synthesize a large number of secondary metabolites numbering above

200,000 that do not play a direct role in their growth but help them to survive
in the environment especially by providing defense against diseases and
pests. The wide variety of secondary compounds is synthesized mainly by the
isoprenoid, phenylpropanoid, alkaloid or fatty acid, or polyketide pathways.
The biosynthesis of phytochemicals is detailed in the next chapter.
Plant disease management involves the reduction in the economic
loss of plants due to diseases caused by pathogens. Plants have evolved
several mechanisms which have led to the production of tens of thousands
of phytochemicals. Earlier, plant-based chemicals constitute a very small
portion which was overlooked. Since the introduction of Food Quality
Protection Act of 1996, there has been a vast market opportunity for agro-
allied-based chemicals used in plant disease management in the United
States and most of North America (Isman, 2000).
A lot of essential oils in plants have shown a high potential for getting
rid of insects. A range of essential oils such as cinnamaldehyde, α-pinene,
extracts from clove (Syzygium aromaticum, major oil being eugenol) and
star anise (Illicium verum) has been shown to have fumigant and antifeedant
effect on red flour beetle (Tribolium castaneum), and the maize weevil
(Sitophilus zeamais) (Ho et al., 1995, 1997; Huang and Ho, 1998; Huang
et al., 1998). Eugenol and oils from the holy basil (Ocimum suave) have
also shown to be effective against Sitophilus granarius and Prostephanus
truncatus (Obeng-Ofori and Reichmuth, 1997). Essential oils of cumin,
star anise, oregano, and eucalyptus have been shown to be active against
greenhouse pests such as cotton aphid (Aphis gossypii) and carmine spider
mite (Tetranychus cinnabarinus) (Tuni and Sahinkaya, 1998). Volume 3 of
this book contains comprehensive chapters on the role of essential oil in pest
and disease management.
Plant-derived aldehydes and ketones play key roles against pathogenic
fungi. Among aliphatic aldehydes and ketones, cinnamaldehyde has been
shown to have the most potent activity against fungi especially two species
of Penicillium that causes disease in humans (P. cyclopium and P. frequen-
tans). The effects of perillaldehyde and citral were slightly weaker but
potent enough. Penicillium ulaiense, an important pathogen causing molds
in citrus, and other Penicillium spp. causing molds in apple and pear can be
targeted using these aliphatic aldehydes that have one or more double bonds
18 Phytochemistry, Volume 1

conjugated to their carbonyl group. Among aromatic aldehydes, cuminalde-

hyde had been shown to have fairly potent antifungal activity (Kurita et al.,
1981). The essential oils of Thymbra spicata and Satureja thymbra plants
used as spices in Mediterranean cuisine have been shown to inhibit phyto-
pathogenic fungi such as Fusarium moniliforme, Rhizoctonia solani, and
Phytophthora capsici at a concentration of 400–800 µg/mL. Thymol and
carvacrol have been identified as the major constituents in the essential oils
involved in the fungicidal property, followed by monoterpenes γ-terpenin
and p-cymene (Muller et al., 1995).
Phenolic compounds play a significant role in plant defense against
bacteria and fungi. One important phenolic compound is coumarin. Haloge-
nated coumarin, often brominated, chlorinated, or iodinated, is more stable
than coumarin. It has been shown to be particularly effective against plant
pathogenic fungi such as Macrophomina phaseolina (charcoal rot), Phytoph-
thora spp. (damping off and seedling rot), Rhizoctonia spp. (damping off
and root rot), and Pythium spp. (seedling blight). These four fungi are from
different families, showing the broad spectrum activity of halogenated
coumarins. In addition, halogenated coumarins have polymer seed coating
abilities and less phytotoxicity, making them good candidates for natural
pesticide development. In another study, 7-hydroxylated coumarin has been
shown to be effective against parasitism of Orobanche cernua in sunflower
(Serghini et al., 2001).
Tannins are another class of phenolic compounds that provide defensive
properties. Though tannins are mostly known to provide defense against
herbivores due to their astringent properties, they also play some fungicidal
roles. They are active against Colletotrichum circinans, a fungus that causes
smudge in onions. Tannins are also known to be inhibitory for fungal spore
germination. Tannins are also known to be inhibitory for fungal spore germi-
nation (Mazid et al., 2011).
Throughout evolution, plants have come up with multiple defense
mechanisms against different pathogens and predators. With the develop-
ment of high throughput technologies, the understanding of the mechanisms
of plant–pathogen interactions has widen. Subsequent chapter address this
in details.

1.6  PHYTOCHEMIST, SKILLS, AND FUTURE PROSPECTS

A chemist or chemical scientist is one that is involved in research activi-

ties related to chemical analysis, confirmation of elements, elucidation
Introduction to Phytochemistry 19

of the structure of chemical compounds for industrial purposes. But a

phytochemist is a specialist who is interested in the study of chemical
interactions in plants based on the knowledge of chemical science which
is employed for a successful isolation of its components and the determi-
nation of its molecular structure through the study of its properties. The
phytochemists have a good command over medicinal plants through the
study of plant physiology, morphology, internal structure elucidation, and
metabolic activities. A phytochemist is one who is knowledgeable about
the identification, characterization of different natural products by using
biochemical analysis to understudy the chemical composition of different
plant products. The utilization of plants for medicinal purposes is not a
new approach. However, periodically, plants are explored for extraction of
chemical compounds which are beneficial to humans in several aspects.
Once a plant-derived product is confirmed to exhibit curative potentials,
the product will be recommended for drug designing, clinical approach, and
finally to pharma industries.

1.6.1  SKILLS AND EXPERTISE REQUIRED OF A PHYTOCHEMIST

A phytochemist is required to be knowledgeable about the basics of plant

science, isolation, and identification of molecules from plants. The knowledge
and expertise on different analytical techniques for extraction, characterization,
and quality assessment is a prerequisite. In addition, a phytochemist should
be familiar with natural products induction, metabolomics profiling (nuclear
magnetic resonance [NMR], mass spectrometry [MS]), micro-fractionation,
natural products database, e-bioprospecting. Expertise in the state-of-art
techniques including the various extraction methods, for example, solvent
extraction methods, superficial fluid extraction, microwave-assisted
extraction, chromatographic fingerprinting, and marker compound analysis is
required. Advances in chromatographic techniques (liquid chromatography–
MS; liquid chromatography–NMR), gas chromatography–mass spectroscopy,
anti-microbial and antioxidant studies will help in a comprehensive analysis
of natural product extracts. In the recent years, studies are being conducted in
relation to the stress induction of natural products under metabolomics view
(plant metabolomics). The use of metabolomics in conjunction with direct
NMR profiling approaches is important for the understanding of metabolic
reactions in plants. Chapter 8 of this book provides an overview of plant
metabolomics and its applications.
20 Phytochemistry, Volume 1

1.6.2  FUTURE PROSPECTS FOR PHYTOCHEMISTS

Today, a huge sector of the population is relying on medicinal plants for

their preventive and curative properties. WHO stated that those traditional
medicine/ethnomedicine are still being used to treat different ailments.
Nearly 70% of the populations rely on these medicinal practices. People
from remote areas and semi-urban regions of the globe still depend on either
crude or purified product from the plant’s origin. Standardization and quality
control is an important factor in ethnomedicinal formulations. At present,
the phytochemists aim to apply modern techniques to preserve and maintain
the standard and quality of these plant products. Findings by phytochemists
through research investigations are supporting the ethnomedicinal
formulations used by the tribal doctors. Several chemical compounds
derived from plants are undergoing clinical trials and some of them are in
preclinical treatment. Similarly, research is to be focused on the possibility
of developing new products in combination with natural compounds from
ethnomedicine. They identified the diversity of chemical compounds
observed with phytochemicals which have led to the formulations of novel
drugs against multidrug-resistant pathogens.
Phytochemists are seriously embarking on research activities involving
the extraction of natural compounds present in plants. Some of these
phytochemicals have the ability to suppress the activity of cancer cells by
encouraging cell cycle inhibition and apoptosis. There is a lot of demand
for natural products of plant origin and these by-products are to replace the
synthetic products in view of their side effects on human health. Therefore,
a lot of attention is needed toward natural products in which a phytochemist
plays a key role in this context. Owing to the increasing demand for novel
drugs, so many important and vital compounds regularly being manufac-
tured by the industries generate employment opportunities for experts in
this field. In addition, the increasing acceptance of the chemical diversity of
natural products is well suited to provide the core scaffolds for future drugs.
There will be further developments in the use of novel natural products and
chemical libraries based on natural products in drug discovery campaigns.

1.7  COMPUTER-AIDED PHYTOCHEMICAL STUDIES

Advances in the knowledge of genome sequencing have led to increase

in knowledge of therapeutic targets for pharmaceutics research (de Ruyck
et al., 2016). Just as the knowledge of high-throughput crystallography
Introduction to Phytochemistry 21

and NMR methods have developed over the time and contributed to the
acquisition of atomic structures of proteins and protein–ligand interactions
to an increasing level of detail (Gore and Desai, 2014), the knowledge of
computational phytochemistry has also grown to give insight into protein
interactions with their ligands. Computational phytochemistry method has
been utilized by research-based pharmaceutical industries to study struc-
ture–activity relationships (Hughes et al., 2011).
This aspect of phytochemistry among other computer-aided drug
discovery program have gain extensive use in studies of drug candidates, to
increase their efficiency and development pipeline, based on their purpose
and required interest (Zhang, 2011). Among such programs are docking
techniques. Docking program is a software technique that allows the user
to fit a molecule (ligand) into target (protein)-binding sites. It can also be
used to predict the structure of the molecular interactions between these
pairs (ligand/protein). The ligands are often relatively the smaller molecules
which conformations (ligand–receptor complexes), binding energies or
affinities, and nature of interactions are assessed in the binding site of their
receptors, which are relatively larger macromolecules. The various software,
databases, and tools for molecular docking and dynamics simulations are
detailed in Chapter 19 of this book. Its applications are discussed further in
Volume 2.
Molecular docking studies have diverse applications. It is a powerful and
important modeling tool utilized in modern drug discovery. They are cheap,
convenient, and not time-consuming, as several samples could be asses in
lesser time. Prior to in vivo studies, molecular docking studies are used to
access lead compounds for further studies. Its applications to phytochemicals
studies are of immense importance, some of which are summarized below;

1. Identification of natural phytochemical: Molecular docking tools

are used in identifying natural phytochemical as well as in the repur-
posing of existing commercial drugs that are effective in treating
disease. In applying this knowledge to phytochemical studies, the
constituents in a particular plant are tested individually for their
activities against key enzymes in selected diseases.
2. Development of phytochemical database: There exist the impor-
tance of means to obtain phytochemicals in the format required
for in silico studies. Data-based design for this purpose have been
identified (Barlow et al., 2012). The availability of phytochemical
dataset with their various two-dimensional/three-dimensional struc-
ture, possible target proteins, simplified molecular input line entry
22 Phytochemistry, Volume 1

specification, MOL2 files, and chemical class may enable their use
in docking studies. This will ease the process of identification of
lead compounds from natural products and their development into
phytomedicines (Pathania et al., 2015).
3. Sorting out lead compounds: Molecular docking studies are applied
to a large database, in order to identify hit compounds. The defined
program and the various scores obtained from each compound can
be compared to identify such hit compounds.
4. Optimization of lead phytochemicals: Molecular docking can be
used to predict and subsequently develop a more potent, and effec-
tive drug candidates from selected phytochemicals. The develop
candidate end up with optimized ligand–protein interactions.
5. Identification of the mechanism of action: When in search of the
mechanism of action of certain active phytochemicals, molecular
docking studies may be applied in order to identify the nature of the
interaction of the compound with the protein. Their binding affinities
and nature of interactions can similarly be analyzed.

1.8  BIOSTATISTICS AS A TOOL FOR PHYTOCHEMISTS

Biostatistics is the application of statistics to topics relating to biology.

Biology, is a natural science concerned with life and living organisms,
branches out to a handful of other related fields such as ecology, zoology,
anatomy, microbiology, biochemistry, and so on. Statistics as the best breed
of mathematical analysis provides objective and rational methods that
enable research questions to be answered and rational questions to be asked
for research after research.
The scope of biostatistics ranges from formulating the research ques-
tion until the presentation or publication of the results. Biostatisticians and
practitioners spend a considerable amount of time in developing research
designs, evaluating methodologies, and analyzing statistical results.
However, just like how it is used in any other fields, statistics in biology can
often be misused. And as the application moves into life applications such as
medical and pharmacological studies, statistics must be practiced efficiently
and truthfully.
A misconception exists that the role of statistics come into play after
data collection – when the analysis is done to determine rationale find-
ings regarding the data. However, statistics should be well accounted all
throughout the research process. Good research problems start with simple
Introduction to Phytochemistry 23

and measurable objectives. Even for qualitative studies, there must be a clear
set of indicators to be used in the research. A sound literature review needs
good statistics for the research to gain some traction regarding its signifi-
cance. Methodologies and data analysis must be systematic and abiding with
the fundamentals of the different fields not only biology but most commonly
with chemistry and mathematics. Lastly, publication and result dissemina-
tion require a grasp of the understanding of how statistics can be used to
relay findings in scientific yet technical manner. Essentially, the role of
biostatistics is to keep every aspect of a research, from the objectives down
to result publication, as efficient and valid as possible.

1.8.1  BIOSTATISTICS IN PHYTOCHEMICAL RESEARCH

Phytochemical research has been able to coexist with biostatistics smoothly.

The study of how chemicals from plants may potentially affect humans
and other organisms has been objectified and quantified through statistics.
Specifically, it is in pharmacology and drug development that biostatistics
has been considered not only vital but necessary. The application of biosta-
tistics in pharmacology answers three key notions – validity, significance,
and consistency.
The use of biostatistics for validity refers to a sound formulation of
objectives, research idea, and importance. One researcher may pick a
random plant, derive a concoction, and then test its antimicrobial proper-
ties. However, a good phytochemical research involves an assessment of the
community needs and formulating measurable objectives. This can only be
done by looking into the statistics (statistics in its plural form) related to the
plant. This could be about its folkloric use, history, preparation as well as
how many studies were done regarding this plant. The validity also comes
from the statistics found from these accompanying literature whether future
studies can bare fruitful results. Measurable objectives also contribute to
validity. Using statistical concepts such as the types of variables and varying
levels of the measure will ensure sound objectives and will later on be the
basis for statistical analysis.
Testing for significance has been the highlight between the relationship
of pharmacology and statistics. To test for significance, treatments (usually
in dosages) are compared with a positive treatment (a commercially manu-
facture drug) and a negative control. This phase of the research is fairly
straightforward; nonetheless, the analysis is highly dependent on a sound
methodology and appropriate statistical test/analysis. Most often researches
24 Phytochemistry, Volume 1

do not amount to anything due to bad or mismatched statistical testing. This

is where the role of a biostatistician is crucial as they bridge the gap of
knowledge between masters of two different fields. A research could only be
valid if the statistical methodology on it fits the actual objectives.
With that, consistency allows the public to assess at a glance the
research and development that has come through for a specific pharmaco-
logical study. For example, ASCOF® Lagundi herbal drug that came from
Vitex negundo went through almost 42 years of research and development.
Summative studies were done to determine the consistency of the findings
regarding its anti-inflammatory and anti-histaminic properties before it
was commercially made available to the public. Simply, using statistics to
evaluate results ensures public safety and protects the best interests of every
stakeholder.

1.8.2  ROLE OF A BIOSTATISTICIAN

A lot of statistical tests are utilized for pharma research. A biostatistician

must be equipped with three core skills to ensure a productive study. First,
he must be equipped with a portfolio of parametric/nonparametric tests and
other statistical methods. Sampling or sampling calculations is often an
overlooked aspect of pharmacological studies. A practitioner must be able to
understand the purpose of the study, the research design, and methodology
only then can he start with the sampling technique. A practitioner should at
least be equipped with a standard set of parametric and its nonparametric
counterpart, with their corresponding post hoc analyses. Classic tests such
as analysis of variance, t-tests, and logistic regression analysis have always
been effective in pharmacological studies.
Second is that a practitioner must be able, and willing, to understand both
sides of the coin – statistics and biology. Compromise has been the key in
clinical trials to fit goals with appropriate statistical tests. A practitioner must
be able to discuss results on a life science perspective without losing the
technicality statistics brings onto the study. Last, practitioners must be able
to adapt to technology and developments in the growing field of biostatistics.

1.8.3  TOOLS FOR BIOSTATISTICS

Research and development in biostatistics have always associated with the

release of multiple automated software that made the mitigation between
Introduction to Phytochemistry 25

biology and statistics easier. Microsoft’s Excel spreadsheet has been able
to adapt to the increasing demand by publishing downloadable macros
that can be used for biostatistics, econometrics, and applied statistics.
SPSS and R GUI has been the go-to professional package and academic
statistical packages, respectively. SPSS offers user-friendly interface that
enables non-practitioners to run data, meanwhile, R GUI has been the
most dynamic statistical software tool as it takes advantage of the user’s
in-depth understanding of statistics to program through codes the different
tests. With the increasing demand, specific programs have been made
available for commercial usage. OpenEpi and Stata have been widely
used in clinical trials. Meanwhile, EpiInfo has been the go-to software for
medical professionals, researchers in clinical trials, and even by industrial
manufacturers. Chapter 18 of this book detailed the various statistical tools
used in phytochemical research with web links to download them while
using essential oil studies to make references to the features of few.

1.9  MAJOR PHYTOCHEMICAL SOCIETIES AND FUNDING

AGENCIES

There are several phytochemical groups, institutes, research centers all

over the world. The activities of Phytochemical Society of North America
(PSNA), Phytochemical Society of Europe (PSE), and Phytochemical
Society of Asia (PSA) deserves mention.

1.9.1  PHYTOCHEMICAL SOCIETY OF NORTH AMERICA

The PSNA is a nonprofit organization with membership subscription fee. Its

membership is open to anyone with an interest in phytochemistry. It aims to
promote research on the chemistry and biochemistry of plant constituents, the
physiology and pathology effects upon plant and animals, and the industrial
applications of phytoconstituents. PSNA transcended from Plant Phenolics
Group of North America to this day PSNA with Mabry, T. J. as it is first
President as a Society in 1966. PNSA provides professional development
opportunities such as research presentations (oral or poster), annual confer-
ences, travel awards, the Frank and Mary Loewus Student Travel Award
for undergraduate students, graduate students, and postdoctoral researchers.
More information can be accessed from its website: http://www.psna-online.
org/index.html.
26 Phytochemistry, Volume 1

1.9.2  PHYTOCHEMICAL SOCIETY OF EUROPE

PSE is a membership organization for everyone with the interest in phyto-

chemistry. It promotes the advancement of the chemistry and biochemistry
of plants constituents and its applications in industry and agriculture.
PSE organizes two to three conferences yearly in the United Kingdom
and Continental Europe and gives awards to deserving phytochemists. The
society metamorphosed from Plant Phenolics Group to Phytochemical
Group and to a Society in 1967 and finally adopted its present name in
1977. More information can be accessed from its website: http://phyto-
chemicalsociety.org/.

1.9.3  PHYTOCHEMICAL SOCIETY OF ASIA

The PSA was founded in 2007 at Kuala Lumpur, Malaysia with Prof.
Yoshinori Asakawa (Japan) elected as the founding President and Prof. Iqbal
Choudhary M. (Pakistan) as the Vice President. The aim of the society is
to promote collaborative research between scientists and in the growth and
advancement of research in the field of natural products from of the region
and outside the region. It has different types of membership such as regular
membership, student membership, honorary members, life members, insti-
tutional membership with different subscription rates. More information can
be accessed from its website: http://phytochemsoc-asia.com/.

1.9.4  FUNDING AGENCIES FOR RESEARCHERS IN

PHYTOCHEMISTRY

Government funding programs are available in many countries for

phytochemical and related investigations. Besides, international
organizations such as Intergovernmental Science-Policy Platform on
Biodiversity and Ecosystem Services, International Union for Conservation
of Nature and WHO are offering funds towards the progress of these
investigations.

1.10  ADVANCES IN PHYTOCHEMICAL RESEARCH

So far, a substantial progress has been made for the discovery of new phyto-
chemicals which could serve as a lead compounds for the development of
new drugs. Drug discovery is capital intensive which usually starts with
Introduction to Phytochemistry 27

the screening and identification of active ingredient in traditional plants.

According to Business Wire, the global drug discovery informatics market is
expected to reach the US $2.84 Billion in 2022 from the US $1.67 Billion in
2017 at a CAGR (Compound Annual Growth Rate is the mean annual growth
rate of an investment over a specified period of time longer than 1 year) of
11.2%. The discovery of new drugs usually is carried out by pharmaceutical
and biotechnology companies with the assistance from the universities. The
search for the discovery of new drugs must be continued to stem out the
ravaging effects of diseases in plants and animals. Many more phytochemi-
cals abound yet undiscovered in plants because only a small fraction of the
plants has been studied. The development of new analytical techniques and
validation of the existing ones will greatly help in phytochemical research.
Computer-aided drug discovery is part of the modern drug discovery
tool which helps to drive a fast and efficient discovery process through the
identification of screen hits by molecular docking, modeling, and dynamics
simulations. Target compounds are assessed for their binding affinity to
target receptor cells, its selectivity, efficacy or potency, metabolic stability,
and oral bioavailability. Once a compound is identified to fulfill the require-
ments, it will undergo phase I, II, and III clinical trials.
One drawback in the development of new drugs, is that many plant-
derived compounds still cannot be synthetized and so are not commercially
available. This is why the access to some drugs is quite expensive. More
needs to be made in the area of phytochemistry including government and
non-governmental agencies for fundings, grants, consultation, and collabo-
ration in research projects and so on. The other way to improve the quality
of research output is to establish the field of phytochemistry as a single
stand-alone science. Although few institutions have done so there is a need
for more tertiary institutions to do so.
Phytochemicals are naturally present in many foods but it is expected that
through bioengineering, new plants will be developed, which will contain
higher levels. This would make it easier to incorporate enough phytochemi-
cals into the food.

1.10.1  PROGRESS IN PHYTOCHEMICAL RESEARCH

1.10.1.1  AS NANOPARTICLE (NP) SYNTHETIC PRECURSORS

Phytochemicals can act as cheap and raw materials for different classes of
nanoparticle (NP) synthesis, which has been discussed in details in Volume 2.
28 Phytochemistry, Volume 1

Phytochemicals can be selectively utilized to synthesize the NP of interest,

for example, having red emission, having good ability to carry drugs, and
so forth.

1.10.1.2  AS A FABRICATING SOURCE OF NPS

Literature goes in favor of the phytochemicals as NPs surface decorating

agents for enhancing the phytochemical activity of the related NPs. It is
also very interesting that this field of research is nascent, and requires a lot
of research which would definitely boost both the areas of phytomedicine
and nanotechnology. A lot of reports are available for the applications of
phytochemicals as fabricating source (Ahmad et al., 2017).

1.10.1.3  ANTITUMOR EFFECTS

Cancer is a leading cause of deaths worldwide. A lot of research has been

done to overcome this notorious disease, while still much is needed to
completely haul this disease. Chapters 20, 21, and 23 are research discov-
eries of potential anticancer drugs. Many chapters in Volume 2 and 3 of this
book contain novel research in this direction.
Phytochemicals could contribute to the cancer treatment in the following
ways:

a) Drugs source: certain important chemicals, such as taxol can directly

be isolated from plants, and could be potentially used as an anti-
cancer agent (Bo et al., 2016).
b) Along with a source of drugs isolation, phytochemicals could also
be used to obtain NPs having anticancerous effects, as well as NPs
using as agents for anticancerous drugs delivery, as well as photolu-
minescent agents in their treatment (Angelova et al., 2017, Kapinova
et al., 2017, Kaur et al., 2017).

1.10.1.4  CUTANEOUS CARCINOMA

The prevention of this heinous disease by phytochemicals is of main concern

these days as compared to their chemoprevention. It has been considered
that phytochemicals are safely relieving multiple pathological processes,
Introduction to Phytochemistry 29

including oxidative damage, epigenetic alteration, chronic inflammation,

angiogenesis, and so forth (Wang et al., 2017).

1.10.1.5  OTHER DISEASES

Research outcomes from the study of the pharmacological effects of phyto-

chemicals in the treatment of various diseases are largely being dependent on
as interest is growing due to the safety of natural herbal products compared
to the synthetic ones with side effects. Many medications for some ravaging
diseases remain a mirage despite the enormous work in drug discovery.
Diseases such as diabetes, a well-known disease of rich and poor, as well as
found in developed and developing nations, have a lot of space to be treated
phytochemically. The study of plant-derived chemicals is continuous with
many sophisticated techniques being developed to assist in the discovery of
compounds which will be of medical significance and to other industries for
the betterment of life. An ample discoveries have been made but more is yet
to be done.

KEYWORDS

•• phytochemistry
•• phytochemicals
•• terpenes
•• flavonoids
•• alkaloids

REFERENCES

Achan, J.; Talisuna, A. O.; Erhart, A. et al. Quinine, an Old Anti-Malarial Drug in a
Modern World: Role in the Treatment of Malaria. Malar. J. 2011, 10, 144. DOI: 10.1186/
1475-2875-10-144.
Adamczyk, B.; Karonen, M.; Adamczyk, S.; Engström, M. T.; Laakso, T.; Saranpää, P.;
Kitunen, V.; Smolander, A. J. Tannins Can Slow-Down but Also Speed-up Soil Enzymatic
Activity in Boreal Forest. Soil. Biol. Biochem. 2017, 107, 60–67.
Ahmad, B.; Hafeez, N.; Bashir, S.; Rauf, A. et al. Phytofabricated Gold Nanoparticles and
Their Biomedical Applications. Biomed. Pharmacother. 2017, 89, 414–425.
30 Phytochemistry, Volume 1

Althagafy, H. S.; Graf, T. N.; Sy-Cordero, A. A.; Gufford, B. T.; Paine, M. F.; Wagoner, J.;
Polyak, S. J.; Croatt, M. P.; Oberlies, N. H. Semisynthesis, Cytotoxicity, Antiviral Activity,
and Drug Interaction Liability of 7-O-Methylated Analogues of Flavonolignans from Milk
Thistle. Bioorg. Med. Chem. 2013, 21(13), 3919–3926.
Angelova, A.; Garamus, V. M.; Angelov, B.; Tian, Z.; Li, Y.; Zou, A. Advances in Structural
Design of Lipid-Based Nanoparticle Carriers for Delivery of Macromolecular Drugs,
Phytochemicals and Anti-Tumor Agents. Adv. Colloid Interface Sci. 2017, 249, 331–345.
Araya-Cloutier, C.; Den Besten, H. M.; Aisyah, S.; Gruppen, H.; Vincken, J. P. The Position
of Prenylation of Isoflavonoids and Stilbenoids from Legumes (Fabaceae) Modulates the
Antimicrobial Activity Against Gram Positive Pathogens. Food Chem. 2017, 226, 193–201.
Arens, U. Authorised EU Health Claim for Carbohydrates and Maintenance of Normal Brain
Function. Food Nutr. Food Ingredients Authorised EU Health Claims 2018, 229, 236.
Avraham, Y.; Berry, E. M.; Donskoy, M.; Ahmad, W. A.; Vorobiev, L.; Albeck, A.; Mankuta,
D. Beta-Carotene as a Novel Therapy for the Treatment of "Autistic Like Behavior" in
Animal Models of Autism. Behav. Brain Res. 2017.
Bahramsoltani, R.; Rahimi, R.; Farzaei, M. H. Pharmacokinetic Interactions of Curcuminoids
with Conventional Drugs: A Review. J. Ethnopharmacol. 2017, 209, 1–12.
Barazzoni, R.; Deutz, N. E. P.; Biolo, G.; Bischoff, S.; Boirie, Y.; Cederholm, T.; Cuerda, C.;
Delzenne, N.; Leon Sanz, M.; Ljungqvist, O.; Muscaritoli, M.; Pichard, C.; Preiser, J. C.;
Sbraccia, P.; Singer, P.; Tappy, L.; Thorens, B.; Van Gossum, A.; Vettor, R.; Calder, P. C.
Carbohydrates and Insulin Resistance in Clinical Nutrition: Recommendations from the
ESPEN Expert Group. Clin. Nutr. 2017, 36(2), 355–363.
Barlow, D. J.; Buriani, A.; Ehrman, T.; Bosisio, E.; Eberini, I.; Hylands, P. J. In-Silico
Studies in Chinese Herbal Medicines’ Research: Evaluation of in-silico Methodologies and
Phytochemical Data Sources, and a Review of Research to Date. J. Ethnopharmacol. 2012,
140, 526–534.
Barrett, A. H.; Farhadi, N. F.; Tracey J. Smith. Slowing Starch Digestion and Inhibiting
Digestive Enzyme Activity Using Plant Flavanols/Tannins-A Review of Efficacy and
Mechanisms. LWT Food Sci. Technol. 2018, 87, 394–399.
Basheer, L.; Schultz, K.; Guttman, Y.; Kerem, Z. In Silico and in Vitro Inhibition of
Cytochrome P450 3A by Synthetic Stilbenoids. Food Chem. 2017, 237, 895–903.
Bieganska-Marecik, R.; Radziejewska-Kubzdela, E.; Marecik, R. Characterization of
Phenolics, Glucosinolates and Antioxidant Activity of Beverages Based on Apple Juice
with Addition of Frozen and Freeze-Dried Curly Kale Leaves (Brassica oleracea L. var.
acephala L.). Food Chem. 2017, 230, 271–280.
Bijak, M.; Szelenberger, R.; Saluk, J.; Nowak, P. Flavonolignans Inhibit ADP Induced Blood
Platelets Activation and Aggregation in Whole Blood. Int. J. Biol. Macromol. 2017, 95,
682–688.
Bo, L.; Cui, H.; Fang, Z.; Qun, T.; Xia, C. Inactivation of Transforming Growth Factor-
Beta-Activated Kinase 1 Promotes Taxol Efficacy in Ovarian Cancer Cells. Biomed.
Pharmacother. 2016, 84, 917–924.
Boucherle, B.; Peuchmaur, M.; Boumendjel, A.; Haudecoeur, R. Occurrences, Biosynthesis
and Properties of Aurones as High-End Evolutionary Products. Phytochemistry 2017, 142,
92–111.
Business Wire. $2.84 Billion Drug Discovery Informatics Market 2017 by Function, Solution
and End User - Global Forecast to 2022 – Research and Markets. https://www.businesswire.
com/news/home/20180108006006/en/2.84-Billion-Drug-Discovery-Informatics-
Market-2017. (Accessed Jan 9, 2018).
Introduction to Phytochemistry 31

Canales, R.; Guinez, M.; Bazan, C.; Reta, M.; Cerutti, S. Determining Heterocyclic Aromatic
Amines in Aqueous Samples: A Novel Dispersive Liquid-Liquid Micro-Extraction Method
Based on Solidification of Floating Organic Drop and Ultrasound Assisted Back Extraction
Followed by UPLC-MS/MS. Talanta 2017, 174, 548–555.
Cao, H.; Jia, X.; Shi, J.; Xiao, J.; Chen, X. Non-Covalent Interaction Between Dietary
Stilbenoids and Human Serum Albumin: Structure-Affinity Relationship, and its Influence
on the Stability, Free Radical Scavenging Activity and Cell Uptake of Stilbenoids. Food
Chem. 2016, 202, 383–388.
Chrbolka, P.; Paluch, Z.; Hill, M.; Alusik, S. Circulating Steroids Negatively Correlate with
Tinnitus. Steroids 2017, 123, 37–42.
Coronado-Aceves, E. W.; Gigliarelli, G.; Garibay-Escobar, A.; Zepeda, R. E. R.; Curini, M.;
Lopez Cervantes, J.; Ines Espitia-Pinzon, C. I.; Superchi, S.; Vergura, S.; Marcotullio, M.
C. New Isoflavonoids from the Extract of Rhynchosia Precatoria (Humb. & Bonpl. ex
Willd.) DC. and their Antimycobacterial Activity. J. Ethnopharmacol. 2017, 206, 92–100.
Cvijetic, I. N.; Verbic, T. Z.; Ernesto De Resende, P.; Stapleton, P.; Gibbons, S.; Juranic, I. O.;
Drakulic, B. J.; Zloh, M. Design, Synthesis and Biological Evaluation of Novel Aryldiketo
Acids with Enhanced Antibacterial Activity Against Multidrug Resistant Bacterial Strains.
Eur. J. Med. Chem. 2018, 143, 1474–1488.
David, B.; Jacoby, R. M. Y. Encyclopedia of Family Health. Third 2005.
De Meloa, I. S. V.; Dos Santosb, A. F.; Buenoc, N. B. Curcumin or Combined Curcuminoids
are Effective in Lowering the Fasting Blood Glucose Concentrations of Individuals with
Dysglycemia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Pharmacol. Res. 2017.
De Oliveira, N. A.; Cornelio-Santiago, H. P.; Fukumasu, H.; De Oliveira, A. L. Green Coffee
Extracts Rich in Diterpenes–Process Optimization of Pressurized Liquid Extraction Using
Ethanol as Solven. J. Food Eng. 2017.
de Ruyck, J.; Brysbaert, G.; Blossey, R.; Lensink, F. M. Molecular Docking as a Popular Tool
in Drug Design, an in Silico Travel. Adv. Appl. Bioinf. Chem. 2016, 9, 1–11.
Dikshit, M. Foreword. In Herbs for Diabetes and Neurological Disease Management:
Research and Advancements; Kumar, V., Addepalli, V., Eds.; Apple Academic Press: New
York, 2017.
Dobson, SMaM. In Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New
Directions in Drug Discovery; PJ, R., Ed.; Humana Press: Totowa, New Jersey, The history
of antimalarial drugs. 2001; pp 15–25.
Dos, Reis, L. C. R.; De Oliveira, V. R.; Hagen, M. E. K.; Jablonski, A.; Flôres, S. H.; De
Oliveira Rios, A. Carotenoids, Flavonoids, Chlorophylls, Phenolic Compounds and
Antioxidant Activity in Fresh and Cooked Broccoli (Brassica Oleracea var. Avenger) and
Cauliflower (Brassica Oleracea Var. Alphina F1). LWT–Food Sci. Technol. 2015, 63(1),
177–183.
Ergene Oz, B.; Saltan Iscan, G.; Kupeli Akkol, E.; Suntar, I.; Bahadir Acikara, O. Isoflavonoids
as Wound Healing Agents from Ononidis Radix. J. Ethnopharmacol. 2018, 211, 384–393.
Fabricant, D. S.; Farnsworth, N. R. The Value of Plants Used in Traditional Medicine for
Drug Discovery. Environ. Health Perspect. 2001, 109, 69–75.
Fabro, S.; Smith, R. L.; Williams, R. T. Toxicity and Teratogenicity of Optical Isomers of
Thalidomide. Nature 1967, 215, 296. https://www.nature.com/articles/215296a0 (accessed
Nov 19, 2017).
Faiella, L.; Piaz, F. D.; Bader, A.; Braca, A. Diterpenes and Phenolic Compounds from
Sideritis Pullulans. Phytochemistry 2014, 106, 164–170.
32 Phytochemistry, Volume 1

Gengatharan, A.; Dykes, G. A.; Choo, W. S. Betalains: Natural Plant Pigments with Potential
Application in Functional Foods. LWT–Food Sci. Technol. 2015, 64(2), 645–649.
Gerschenson, L. N.; Rojas, A. M.; Fissore, E. N. Carbohydrates. 2017, 39–101.
Gore, M.; Desai, N. S. Computer-Aided Drug Designing. Methods Mol. Biol. 2014, 1168,
313–321.
Grishko, V. V.; Galaiko, N. V. Structural Diversity, Natural Sources and Pharmacological
Potential of Naturally Occurring A-Seco-Triterpenoids. 2016, 51, 51–149.
Gu, J.; Liu, T.; Sadiq, F. A.; Yang, H.; Yuan, L.; Zhang G.; He, G. Biogenic Amines Content
and Assessment of Bacterial and Fungal Diversity in Stinky Tofu–A traditional fermented
soy curd. LWT–Food Sci. Technol. 2018, 88, 26–34.
Gutiérrez-Larraínzar, M.; Rúa, J.; Caro, I.; De Castro, C.; De Arriaga, D.; García-Armesto,
M.; RosarioDel Valle, P. Evaluation of Antimicrobial and Antioxidant Activities of Natural
Phenolic Compounds Against Foodborne Pathogens and Spoilage Bacteria. Food Control.
2012, 26(2), 555–563.
Hartmann, T. From Waste Products to Ecochemicals: Fifty Years Research of Plant Secondary
Metabolism. Phytochemistry. 2007, 68(22–24), 2831–2846.
Ho, S. H.; Ma, Y.; Goh, P. M.; Sim, K. Y. Star Anise, Illicium Verum Hook F. as a Potential
Grain Protectant Against Tribolium Castaneum (Herbst) and Sitophilus Zeamais Motsch.
Postharvest Biol. Technol. 1995, 6, 341–347.
Ho, S. H.; Ma, Y.; Huang, Y. Anethole, a. Potential Insecticide from Illicium Verum Hook F.,
Against Two Stored Product Insects. Int. Pest. Control. 1997, 39(2), 50–51.
Hu, H. B.; Liang, H. P.; Li, H. M.; Yuan, R. N.; Sun, J.; Zhang, L. L.; Han, M. H.; Wu,
Y. Isolation, Modification and Cytotoxic Evaluation of Stilbenoids from Acanthopanax
Leucorrhizus. Fitoterapia 2018, 124, 167–176.
Huang, Y.; Hee, S. K.; Ho, S. H. Antifeedant and Growth Inhibit- Ory e!ects of -Pinene on
the Stored-Product Insects, Tribolium Castaneum (Herbst) and Sitophilus Zeamais Motsch.
Int. Pest Control. 1998, 40(1), 18–20.
Huang, Y.; Ho, S. H. Toxicity and Antifeedant Activities of Cinna- Maldehyde Against the
Grain Storage Insects, Tribolium Castaneum (Herbst) and Sitophilus Zeamais Motsch. J.
Stored Prod. Res. 1998, 34, 11–17.
Hughes, J. P.; Rees, S.; Kalindjian, S. B.; Philpott, K. L. Principles of Early Drug Discovery.
Br. J. Pharmacol. 2011, 162, 1239–1249.
Isman, M. B. Plant Essential Oils for Pest and Disease Management. Crop Prot. 2000, 19,
603–608.
Jiang, Z.; Chai, L.; Liu, Y.; Qiu, H.; Wang, T.; Feng, X.; Wang, Y. et al. Bioactive Lignans
from the Stems of Mappianthus Iodoides. Phytochem. Lett. 2017, 22, 194–198.
Kapinova, A.; Stefanicka, P.; Kubatka, P.; Zubor, P.; Uramova, S.; Kello, M.; Mojzis, J.;
Blahutova, D.; Qaradakhi, T.; Zulli, A.; Caprnda, M.; Danko, J.; Lasabova, Z.; Busselberg,
D.; Kruzliak, P. Are Plant-Based Functional Foods Better Choice Against Cancer than
Single Phytochemicals? A Critical Review of Current Breast Cancer Research. Biomed.
Pharmacother. 2017, 96, 1465–1477.
Kaur ,V.; Kumar, M.; Kumar, A.; Kaur, K.; Dhillon, V. S.; Kaur, S. Pharmacotherapeutic
Potential of Phytochemicals: Implications in Cancer Chemoprevention and Future
Perspectives. Biomed. Pharmacother. 2017, 97, 564–586.
Krishnamurti, C.; Rao, S. C. The Isolation of Morphine by Serturner. Indian J. Anaesth. 2016,
60(11), 861–862. DOI: 10.4103/0019-5049.193696.
Introduction to Phytochemistry 33

Kumar, S. S.; Manoj, P.; Giridhar, P.; Shrivastava, R.; Bharadwaj, M. Fruit Extracts of
Basella Rubra that are Rich in Bioactives and Betalains Exhibit Antioxidant Activity and
Cytotoxicity Against Human Cervical Carcinoma Cells. J. Funct. Foods 2015, 15, 509–515.
Kurita, N.; Miyaji, M.; Kurane, R.; Takahara, Y. Antifungal Activity of Components of
Essential Oils. Agric. Biol. Chem. 1981, 45, 945–952.
Liew, K. F.; Chan, K. L. Lee, C. Y. Blood-Brain Barrier Permeable Anticholinesterase
Aurones: Synthesis, Structure-Activity Relationship, and Drug-Like Properties. Eur. J.
Med. Chem. 2015, 94, 195–210.
Liew, K. F.; Hanapi, N. A.; Chan, K. L.; Yusof, S. R.; Lee, C. Y. Assessment of the Blood-
Brain Barrier Permeability of Potential Neuroprotective Aurones in Parallel Artificial
Membrane Permeability Assay and Porcine Brain Endothelial Cell Models. J. Pharm. Sci.
2017, 106(2), 502–510.
Liu, Y. Z.; Yang, C. M.; Chen, J. Y.; Liao, J. W.; Hu, M. L. Alpha-Carotene Inhibits Metastasis
in Lewis Lung Carcinoma in Vitro, and Suppresses Lung Metastasis and Tumor Growth
in Combination with Taxol in Tumor Xenografted C57BL/6 Mice. J. Nutr. Biochem. 2015,
26(6), 607–615.
Lydon, J.; Duke, S. O. Pesticide Effects on Secondary Metabolism of Higher Plants. J.
Pestic. Sci. 1989, 25(4), 361–373 http://onlinelibrary.wiley.com/wol1/doi/10.1002/
ps.2780250406/abstract (accessed Nov 17, 2017).
Mazid, M.; Khan, T. A.; Mohammad, F. Role of Secondary Metabolites in Defense
Mechanisms of Plants. Biol. Med. 2011, 3(2), 232–249.
Mehrad, B.; Ravanfar, R.; Licker, J.; Regenstein, J. M.; Abbaspourrad, A. Enhancing the
Physicochemical Stability of β-Carotene Solid Lipid Nanoparticle (SLNP) Using Whey
Protein Isolate. Food Res. Int. 2018, 105, 962–969.
Mewalal, R.; Rai, D. K.; Kainer, D.; Chen, F.; Kulheim, C.; Peter, G. F.; Tuskan, G. A. Plant-
Derived Terpenes: A Feedstock for Specialty Biofuels. Trends Biotechnol. 2017, 35(3),
227–240.
Mirzaei, H.; Shokrzadeh, M.; Modanloo, M.; Ziar, A.; Riazi, G. H.; Emami, S. New Indole-
Based Chalconoids as Tubulin-Targeting Antiproliferative Agents. Bioorg. Chem. 2017,
75, 86–98.
Mostofi, M.; Mohammadi Ziarani, G.; Mahdavi, M.; Moradi, A.; Nadri, H.; Emami, S.;
Alinezhad, H.; Foroumadi, A.; Shafiee, A. Synthesis and Structure-Activity Relationship
Study of Benzofuran-Based Chalconoids Bearing Benzylpyridinium Moiety as Potent
Acetylcholinesterase Inhibitors. Eur. J. Med. Chem. 2015, 103, 361–369.
Muller-Riebau, F.; Berger, B.; Yegen, O. Chemical Composition and Fungitoxic Properties
to Phytopathogenic Fungi of Essential Oils of Selected Aromatic Plants Growing Wild in
Turkey. J. Agric. Food Chem. 1995, 43, 2262–2266.
Obeng-Ofori, D.; Reichmuth, Ch. Bioactivity of Eugenol, a Major Component of Essential
oil of Ocimum Suave (Wild.) Against four Species of Stored-Product Coleoptera. Int. J.
Pest Manage. 1997, 43, 89–94.
Olaf, S.; Jan, E.; Keunen, E.; Alan, C. B.; Frederik, J G M Van Kuijk. Fruits and Vegetables
that are Sources for Lutein and Zeaxanthin: the Macular Pigment in Human Eyes. Br. J.
Ophthalmol. 1998, 82, 907–910.
Ouédraogo, J. C. W.; Dicko, C.; Kini, Félix, B.; Bonzi-Coulibaly, Yvonne L.; Dey, E. S.
Enhanced Extraction of Flavonoids from Odontonema Strictum Leaves with Antioxidant
Activity Using Supercritical Carbon Dioxide Fluid Combined with Ethanol. J. Supercrit.
Fluids 2018, 131, 66–71.
34 Phytochemistry, Volume 1

Papageorgiou, M.; Lambropoulou, D.; Morrison, C.; Kłodzińska, E. Namieśnik, J.; Płotka-
Wasylka, J. Literature Update of Analytical Methods for Biogenic Amines Determination
in Food and Beverages. Trends Anal. Chem. 2018, 98, 128–142.
Pathania, S.; Ramakrishnan, S. M.; Bagler, G. Phytochemica: A Platform to Explore
Phytochemicals of Medicinal Plants. Database. 2015, 1–8.
Pitman, N. C. A.; Jørgensen, P. M. Estimating the Size of the World’s Threatened Flora.
Brevia 2002, 298, 989.
Pyszkova, M.; Biler, M.; Biedermann, D.; Valentova, K.; Kuzma, M.; Vrba, J.; Ulrichova,
J.; Sokolova, R.; Mojovic, M.; Popovic-Bijelic, A.; Kubala, M.; Trouillas, P.; Kren, V.
V. J. Flavonolignan 2,3-dehydroderivatives: Preparation, Antiradical and Cytoprotective
Activity. Free Radic Biol Med 2016, 90, 114–125.
Radošević, K.; Srček, V. G.; Bubalo, M. C.; Rimac Brnčić, S.; Takács, K.; Redovniković, I.
R. Assessment of Glucosinolates, Antioxidative and Antiproliferative Activity of Broccoli
and Collard Extracts. J. Food Compos. Anal. 2017, 61, 59–66.
Ravanfar, R.; Comunian, T. A.; Dando, R.; Abbaspourrad, A. Optimization of Microcapsules
Shell Structure to Preserve Labile Compounds: A Comparison Between Microfluidics and
Conventional Homogenization Method. Food Chem. 2018, 241, 460–467.
Roca, M.; Chen, K.; Pérez-Gálvez, A. Chlorophylls; In Handbook on Natural Pigments in
Food and Beverages; Woodhead Publishing: Elsevier, 2016; pp 125–158.
Rodriguez-Amaya, D. B. Carotenes and Xanthophylls as Antioxidants. In Handbook of
Antioxidants for Food Preservatio; 2015, pp 17–50.
Salvador, J. A. R.; Leal, A. S.; Valdeira, A. S.; Goncalves, B. M. F.; Alho, D. P. S.; Figueiredo,
S. A. C.; Silvestre, S. M.; Mendes, V. I. S. Oleanane-, Ursane-, and Quinone Methide
Friedelane-Type Triterpenoid Derivatives: Recent Advances in Cancer Treatment. Eur. J.
Med. Chem. 2017, 142, 95–130.
Schmidt, B.; Ribnicky, D. M.; Poulev, A.; Logendra, S.; Cefalu, W. T.; Raskin, I. A Natural
History of Botanical Therapeutics. Metabolism 2008, 57, S3–S9.
Sekowski, S.; Bitiucki, M.; Ionov, M.; Zdeb, M.; Abdulladjanova, N.; Rakhimov, R.;
Mavlyanov, S.; Bryszewska, M.; Zamaraeva, M. Influence of Valoneoyl Groups on the
Interactions Between Euphorbia Tannins and Human Serum Albumin. J. Lumin. 2018, 194,
170–178.
Serghini, K.; de Luque, A. P.; Castejón‐Muñoz, M.; García‐Torres, L.; Jorrín, J. V. Sunflower
(Helianthus annuus L.) Response to Broomrape (Orobanche cernua Loefl.) Parasitism:
Induced Synthesis and Excretion of 7‐Hydroxylated Simple Coumarins. J. Exp. Bot. 2001,
52(364), 2227–2234.
Singh, P.; Anand, A.; Kumar, V. Recent Developments in Biological Activities of Chalcones:
a Mini Review. Eur. J. Med. Chem. 2014, 85, 758–777.
Sowndhararajan, K.; Deepa, P.; Kim, M.; Park, S. J.; Kim, S. An Overview of Neuroprotective
and Cognitive Enhancement Properties of Lignans from Schisandra Chinensis. Biomed.
Pharmacother. 2017, 97, 958–968.
Tuni, I.; Sahinkaya, S. Sensitivity of Two Greenhouse Pests to Vapours of Essential Oils.
Entomol Exp. Appl. 1998, 86, 183–187.
Veeresham, C. Natural Products Derived from Plants as a Source of Drugs. J. Adv. Pharm.
Technol. Res. 2012, 3(4), 200–201. DOI: 10.4103/2231–4040.104709.
Verma, S.; Mundkinajeddu, D.; Agarwal, A.; Chatterjee, S. S.; Kumar, V. Effects of Turmeric
Curcuminoids and Metformin Against Central Sensitivity to Pain in Mice. J. Tradit.
Complementary Med. 2017, 7(2), 145–151.
 Introduction to Phytochemistry 35

Wang, S.; Shen, P.; Zhou, J.; Lu, Y. Diet Phytochemicals and Cutaneous Carcinoma
Chemoprevention: A Review. Pharmacol. Res. 2017, 119, 327–346.
Xu, F.; Wang, C.; Wang, H.; Xiong, Q.; Wei, Y.; Shao, X. Antimicrobial Action of Flavonoids
from Sedum Aizoon L. Against Lactic Acid Bacteria in Vitro and in Refrigerated fresh Pork
Meat. J. Funct. Foods. 2018, 40, 744–750.
Xu, J.; Cao, J.; Yue, J.; Zhang, X.; Zhao, Y. New Triterpenoids from Acorns of Quercus
Liaotungensis and Their Inhibitory Activity Against α -Glucosidase, α -Amylase and
Protein-Tyrosine Phosphatase 1B. J. Funct. Foods. 2018, 41, 232–239.
Xu, Y.; Li, L.; Cong, Q.; Wang, W.; Qi, X. –L..; Peng, Y.; Song, S.-J. Bioactive Lignans
and Flavones with in Vitro Antioxidant and Neuroprotective Properties from Rubus Idaeus
Rhizome. J. Funct. Foods. 2017, 32, 160–169.
Zebec, Z.; Wilkes, J.; Jervis, A. J.; Scrutton, N. S.; Takano, E.; Breitling, R. Towards Synthesis
of Monoterpenes and Derivatives Using Synthetic Biology. Curr. Opin. Chem. Biol. 2016,
34, 37–43.
Zhang, L.; Xiao, W. H.; Wang, Y.; Yao, M. D.; Jiang, G. Z.; Zeng, B. X.; Zhang, R. S.; Yuan,
Y. J. Chassis and Key Enzymes Engineering for Monoterpenes Production. Biotechnol.
Adv. 2017, 35(8), 1022–1031.
Zhang, S. Computer-Aided Drug Discovery and Development. Methods Mol. Biol. 2011,
716, 23–38.
Zhang, Y.; Wu, S.; Qin, Y.; Liu, J.; Liu, J.; Wang, Q.; Ren, F.; Zhang, H. Interaction of Phenolic
Acids and Their Derivatives with Human Serum Albumin: Structure-Affinity Relationships
and Effects on Antioxidant Activity. Food Chem. 2018, 240, 1072–1080.

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