Phytonutrients as therapeutic agents

Abstract

Abstract Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ω-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, anti-allergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization.

Full text

Review
Charu Gupta* and Dhan Prakash
Phytonutrients as therapeutic agents
Abstract: Nutrientspresentinvariousfoodsplaysanimpor-
tant role in maintaining the normal functions of the human
body. The major nutrients present in foods include carbohy-
drates, proteins, lipids, vitamins, and minerals. Besides
these, there are some bioactive food components known as
“phytonutrients” that play an important role in human
health. They have tremendous impact on the health care
system and may provide medical health benefits including
the prevention and/or treatment of disease and various phy-
siological disorders. Phytonu trients play a positive role by
maintaining and modulating immune function to prevent
specific diseases. Being natural products, they hold a great
promise in clinical therapy as they possess no side effects that
are usually associated with chemotherapy or radiotherapy.
They are also comparatively cheap and thus significantly
reduce health care cost. Phytonutrients are the plant nutrients
with specific biological activities that support human health.
Some of the important bioactive phytonutrients include poly-
phenols, terpenoids, resveratrol, flavonoids, isoflavonoids,
carotenoids, limonoids, glucosinolates, phytoestrogens, phy-
tosterols, anthocyanins, ω-3 fatty acids, and probiotics. They
play specific pharmacological effects in human health such
as anti-microbial, anti-oxidants, anti-inflammatory, anti-
allergic, anti-spasmodic, anti-cancer, anti-aging, hepatopro-
tective, hypolipidemic, neurop rotective, hypotensive, dia-
betes, osteoporosis, CNS stimulant, analgesic, protection
from UVB-induced carcinogenesis, immuno-modulator, and
carminative. This mini-review attempts to summarize the
major important types of phytonutrients and their role in
promoting human health and as therapeutic agents along
with the current market trend and commercialization.
Keywords: anthocyanins, carotenoids, flavonoids, gluco-
sinolates, nutraceuticals, phytoestrogens, phytonutrients,
polyphenols, terpenoids
DOI 10.1515/jcim-2013-0021
Received June 14, 2013; accepted May 20, 2014; previously
published online July 22, 2014
Introduction
Food plays a vital role in maintaining normal function of
the human body. With recent advances in medical and
nutritional sciences, natural products have received
extensive attention as health-promoting foods from both
health professionals and the consumers. Bioactive foods
and nutraceuticals have emerged as potential supple-
ments in various diseases and preventive natural sources
from food [1]. Consumers can use nutraceuticals as sup-
plementation to a poor diet, to improve overall health, to
delay the onset of age-related diseases, after illness, for
stress, in pregnancy and slimming, to improve sports
performance, and to treat symptoms (cold, cough, arthri-
tis, etc.). These functional also called as medicinal foods
contain phytonutrients or phytomedicines that play ben-
eficial roles in maintaining well-being, enhancing health,
and modulating immune function to prevent specific dis-
eases. “Phytonutrients” and “Phytotherapy” is a more
recent term that refers to a science of treatment using a
group of natural substances that include certain herbs
and their derivatives for use as dietary supplements and
regulated as foods [2, 3].
As phytonutrients are of natural origin, they are use-
ful in clinical therapy due to their lower side effects as
compared to chemotherapy or radiotherapy and are
advantageous in reducing the health care cost [4].
There are scientific evidences of their chemical and
biological properties, clinical information, mode of action,
quality control, and effectiveness of phytonutrients in
nutritional therapy [5]. Phytonutrients play an important
role in human health as anti-oxidants, anti-bacterial, anti-
fungal, anti-inflammatory, anti-allergic, anti-spasmodic,
chemo-preventive, hepatoprotective, hypolipidemic, neu-
roprotective, and hypotensive agents and help in prevent-
ing aging, diabetes, osteoporosis, cancer and heart
diseases, induced apoptosis, diuretic, CNS stimulant,
analgesic, protection from UVB-induced carcinogenesis,
immuno-modulator, and carminative [6, 7].
Dietary intake of phytochemicals promotes health ben-
efits and protects against chronic degenerative disorders,
such as cancer, cardiovascular and neurodegenerative
diseases, diabetes, high blood pressure, inflammation,
*Corresponding author: Charu Gupta, Amity Institute for Herbal
Research and Studies, Amity University, Noida, Uttar Pradesh, India,
E-mail: charumicro@gmail.com
Dhan Prakash, Amity Institute for Herbal Research and Studies,
Amity University, Noida, Uttar Pradesh, India
J Complement Integr Med. 2014; 11(3): 151–169
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microbial, viral and parasitic infections, psychotic diseases,
spasmodic conditions, and ulcers. These phytochemicals,
either alone and/or in combination, have tremendous ther-
apeutic potential in curing various ailments.
The important phytonutrients include carotenoids,
tocopherols, ascorbates, lipoic acids, and polyphenols.
They are strong natural anti-oxidants with free radical
scavenging activity and are associated with a lower inci-
dence of degenerative diseases. Phytoestrogens are non-
steroidal phytochemicals quite similar in structure and
function to gonadal estrogen hormone. They offer an
alternative therapy for hormone replacement therapy
(HRT) with beneficial effects on cardiovascular system
and may even alleviate menopausal symptoms.
Terpenoids are the largest class of phytonutrients present
in green foods and grains, and they provide a measure of
protection from certain diseases, especially those related
to chronic damage and growth deregulation. Carotenoids
lower risk of chronic diseases like cardiovascular, certain
cancers, and eye. Limonoids provide substantial anti-
cancer actions; phytosterols compete with cholesterol in
the intestine for uptake and aid in the elimination of
cholesterol from the body; glucosinolates (GLSs) that
are activators of liver detoxification enzymes, provide
protection against carcinogenesis, mutagenesis, and
other forms of toxicity. An unconventional category of
nutraceuticals of microbial origin known as probiotics
also exists. The majority of probiotic microorganisms
belong to the genera Lactobacillus and Bifidobacterium.
The probiotic bacteria are used for the manufacture of a
natural remedy, for controlling weight gain, preventing
obesity, increasing satiety, prolonging satiation, reducing
food intake, reducing fat deposition, improving energy
metabolism, treating and enhancing insulin sensitivity,
and treating obesity.
Although most phytonutrients currently used are
known as vital nutrients for the human body, many
details such as dose, drug–drug interaction, nutraceuti-
cal–drug interaction, and their effects on individuals
under certain health conditions remain elusive [8]. It is
normally assumed that proper nutrient balance is
required to maintain a healthy status of the human
body, and excess intake of any nutrient may not benefit
or even can be harmful to health.
Knowledge from food chemistry, nutrition, and clin-
ical studies provides more insight into our understanding
of biological functions, usage, and potential adverse
effects of nutraceuticals [8, 9]. This advanced knowledge
helps to standardize manufacturing processes and clin-
ical practices and add more value to nutraceutical mar-
kets [10]. The present review would focus on therapeutic
property and major food sources of some of the important
phytonutrients or bioactive food components like antho-
cyanidins, carotenoids, lycopenes, flavonoids, GLSs, iso-
flavonoids, limonoids, polyphenols, ω-3 fatty acids,
phytoestrogens, resveratrol, phytosterols, probiotics,
and terpenoids. All these phytonutrients play specific
pharmacological effects on human health as anti-inflam-
matory, anti-allergic, anti-oxidants, anti-microbial, anti-
spasmodic, chemopreventive, hepatoprotective, hypolipi-
demic, neuroprotective, hypotensive, anti-aging, dia-
betes, osteoporosis, protection of DNA damage, cancer
and heart diseases, induced apoptosis, diuretic, CNS sti-
mulant, analgesic, protection from UVB-induced carcino-
genesis, immuno-modulator, and carminative [6].
Phytonutrients or bioactive food components can be
added or increased to traditional foods through genetic
engineering techniques. An example would be the high
lycopene tomato, a genetically modified tomato with
delayed ripening characteristics that is high in lycopene
and has potent anti-oxidant capabilities.
The present chapter would discuss about these
potential bioactive food components that could provide
benefits in terms of health and well-being and the poten-
tial role of these functional ingredients (Table 1) along
with their current market trends and scenario.
Phytonutrients and their health
benefits
Polyphenols
Major source
Polyphenols are naturally occurring compounds found
largely in fruits, vegetables, cereals, and beverages.
Legumes and chocolate also contribute to the polyphe-
nolic intake. The major sources of dietary polyphenols
are cereals, legumes (barley, corn, nuts, oats, rice, sor-
ghum, wheat, beans, and pulses), oilseeds (rapeseed,
canola, flaxseed, and olive seeds), fruits, vegetables,
and beverages (fruit juices, tea, coffee, cocoa, beer, and
wine) [11–13].
Amounts
Fruits such as apple, grape, pear, cherry, and various
berries contain up to 200–300 mg polyphenols per 100 g
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Table 1 Major phytonutrients of nutraceutical importance, their sources, and health benefits [109, 110].
Phytonutrient Source plant Health benefits
Anthocyanins Blackberry, cherry, orange, purple corn, raspberry, and
red grapes
Anti-allergic, anti-inflammatory, anti-oxidants, and
pigments
Carotene Carrots, leafy greens and red, orange and yellow
vegetables, and pumpkin
Anti-carcinogenic, enhances release of immunogenic
cytokines IL-1 and TNF-α, provides cornea protection
against UV light, and stimulates DNA repair enzymes
Lycopene Apricots, papaya, pink guava, tomato, and watermelon Lowers risk of atherosclerosis and prostate cancer
Resveratrol Blueberry, peanuts, red grapes, and red wine Anti-oxidant, anti-cancer, prevents aging, diabetes, and
heart diseases
Stigmasterol
(phytosterol)
Soybean Anti-cancer, hypolipidemic, and prevention of
osteoporosis
GLSs Broccoli sprouts, cabbage, cauliflower, collards,
cruciferous vegetables, kale, radish, and turnip
Anti-oxidant, prevent DNA damage, and reduce risk of
breast and prostate cancers
Flavonoids Berries, legumes, tea, grapes, olive oil, cocoa, walnuts,
peanuts, spices, fruits, and vegetables. Especially
green vegetables, onion, apple, berries, and tea
Anti-bacterial, anti-oxidant, anti-viral, analgesic
activities, inhibition of hydrolytic and oxidative
enzymes, anti-inflammatory, anti-viral, and anti-
proliferative
Quercetin Red onions, buckwheat, red grapes, green tea, and
apple skin
Strong anti-oxidant, reduces low-density lipoprotein
(LDL) oxidation, vasodilator, and blood thinner
Isoflavonoids Members of the Fabaceae (Leguminosae) family, soy
cheese, soy flour, soy bean, and tofu
Anti-oxidant, anti-proliferative, anti-cancer, and
prevention of osteoporosis
Limonoids Citrus juice and citrus tissues Anti-cancer, insecticidal, insect anti-feedant, and
growth regulating activity on insects, as well as anti-
bacterial, anti-fungal, anti-malarial, and anti-viral.
Polyphenols Cereals, legumes (barley, corn, nuts, oats, rice,
sorghum, wheat, beans, and pulses), oilseeds
(rapeseed, canola, flaxseed, and olive seeds), fruits,
vegetables, and beverages (fruit juices, tea, coffee,
cocoa, beer, and wine)
Anti-oxidant, anti-carcinogenic, anti-inflammatory, anti-
neurodegenerative, anti-diabetic, anti-viral, skin photo-
protective, anti-allergic, anti-platelet, anti-aging,
cytoprotective, and DNA-protective properties.
ω-3-fatty acids Fish such as salmon, rainbow trout, mackerel, herring,
and sardines. Plants – canola, soybean, and flax oils
Osteoarthritis, lowers cholesterol, reduces high blood
pressure, protects from heart attacks, eases joint
pains, fights wrinkles and skin ailments, and improves
memory
Phytoestrogens Soybeans, wheat, barley, corn, alfalfa, and oats Anti-cancer, heart diseases, menopausal symptoms,
and osteoporosis
Terpenoids Green foods, fruits, vegetables, and grains Anti-microbial, anti-fungal, anti-parasitic, anti-viral,
anti-allergenic, anti-spasmodic, anti-hyperglycemic,
anti-inflammatory, chemotherapeutic, and immuno-
modulatory properties
Probiotics Fermented foods – milk, curd, and cheese, fermented
vegetables
Anti-microbial, prevention of traveler’s diarrhea and
antibiotic-associated diarrhea, inflammatory bowel
disease, lactose intolerance, protection against
intestinal infections, irritable bowel syndrome, vaginal
infections, and immune enhancement, inactivation of
pathogens in the gut, rheumatoid arthritis, improving
the immune response, and liver cirrhosis
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fresh weights. Similarly, a glass of red wine or a cup of
coffee or tea contains about 100 mg polyphenols. Their
total dietary intake may be about 1 g per day, which is
about 10 times higher than that of vitamin C and 100 times
higher than those of vitamin E and carotenoids [14, 15].
Mode of action
These molecules are secondary metabolites of plants and
are generally involved in defense against ultraviolet (UV)
radiation or aggression by pathogens. Basic researches
and epidemiological studies have shown the inverse
association between risk of degenerative diseases and
intake of diet rich in polyphenols. The epidemiological
studies provide convincing evidences that diet rich in
anti-oxidants is associated with a lower incidence of
degenerative diseases. Polyphenols, with ~8,000 struc-
tural variants, are characterized by the presence of aro-
matic rings bearing one or more hydroxyl moieties, which
have proven pivotal roles in mediating their properties
(Figure 1) [16]. Although the knowledge of absorption,
bioavailability, and metabolism of polyphenols is not
entirely known, it appears that some polyphenols are
bioactive and are absorbed in their native or modified
form by the microflora of the intestine. The active com-
ponents of dietary phytochemicals (e.g. curcumin, resver-
atrol, capsaicin, catechins, vitamins, and β-carotene) are
believed to suppress the inflammatory processes, moder-
ate cell signaling pathways, proliferation, apoptosis,
redox balance and most often appear to be protective
against cancer, neurodegenerative disorders and cardio-
vascular diseases among others [17, 18]. Polyphenols are
known for their unique property of activation at multiple
levels, through the modulation of MAPK, Akt, and NF-κB
signaling pathways, inhibiting the production of inflam-
matory cytokines and chemokines, suppressing the activ-
ity of COX and iNOS and decreasing the production of
free radicals [19]. Several phytochemicals including gen-
istein [20], curcuminoids [17], and catechins [21] are
known to suppress the activation of Akt, thus, inhibiting
cancer cell growth. Some phenols like resveratrol, curcu-
min, and green tea catechins have been shown to sup-
press COX-2 giving the benefit of decreasing the
production of reactive oxygen species (ROS) [22, 23].
Furthermore, several polyphenols suppress lipid per-
oxidation to maintain the cellular status of anti-oxidant
enzymes like superoxide dismutase, catalase, and glu-
tathione peroxidase [24]. Due to the NF-κB suppressing
effect of polyphenols, some of them (e.g. curcumin, resver-
atrol, quercetin, and green tea polyphenols) have been
shown to decrease the expression of chemokines and cyto-
kines [25]. Polyphenols present in healthy foods or drinks
are readily metabolized to phenolic acids and aldehydes
by the microflora of the intestine, raising the possibility
that these metabolites are responsible for their anti-inflam-
matory properties [26]. A wide variety of polyphenols, most
of which are dietary supplements, have been reported to
possess substantial skin photo-protective effects [27].
Therapeutic property
In the recent years, there has been much awareness about
functional foods and nutraceuticals fortified with natural
polyphenols and their health benefits like their potent
anti-oxidant activity, anti-carcinogenic, anti-inflammatory,
anti-neurodegenerative, anti-diabetic, anti-viral, skin
photo-protective, anti-allergic, anti-platelet, anti-aging,
cytoprotective, and DNA-protective properties [23].
Terpenoids
Major source
The terpenes, also known as isoprenoids, are the largest
class of phytonutrients in green foods and grains. These
compounds are found in higher plants, mosses,
RR
1
OH
OH
H
OCH
3
H
p
-Coumaric acid CH=CH.COOH H H
OH H
Ferulic acid CH=CH.COOH
CH=CH.COOH
H
Chlorogenic acid CH=CH.COO-quinic acid OH H
R
OH
R
2
R
1
R
2
OH
OCH
3
OCH
3
OCH
3
Vanillic acid
Syringic acid
Gallic acid
Protocatechuic acid COOH
COOH
COOH
COOH
Caffeic acid
Figure 1 Phenolic acids: hydroxycinnamic acids.
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liverworts, algae, and lichens, as well as in insects,
microbes, or marine organisms. Terpenoids are derived
from a common biosynthetic pathway based on mevalo-
nate as parent and are named terpenoids, terpenes, or
isoprenoids with the subgroup of steroids among them as
a class [28, 29]. Their importance to plants relates to their
necessity to fix carbon through photosynthetic reactions
using photosensitizing pigments. Animals have evolved
to utilize these compounds for hormonal and growth
regulatory functions (vitamin A), and the presence of
these molecules in animal tissues also provides a mea-
sure of protection from certain diseases, especially those
related to chronic damage and growth deregulation.
The diverse functional roles of some of the terpenoids
are characterized as hormones (gibberellins), photosyn-
thetic pigments (phytol and carotenoids), electron car-
riers (ubiquinone and plastoquinone), and mediators of
polysaccharide assembly, as well as communication and
defense mechanisms [30].
Mode of action
Terpenes have a unique anti-oxidant activity in their
interaction with free radicals. They react with free radi-
cals by partitioning themselves into fatty membranes by
virtue of their long carbon side chain. The most studied
terpene anti-oxidants are the tocotrienols and tocopher-
ols. They are found naturally in whole grains and have
effects on cancer cells. The tocotrienols are effective
apoptotic inducers for human breast cancer cells. The
impact of a diet of fruits, vegetables, and grains on
reduction of cancer risk may be explained by the actions
of terpenes in vivo [6, 13].
Therapeutic property
Several biological actions have been reported for diter-
penes including anti-bacterial, anti-fungal, anti-inflamma-
tory, anti-leishmanial, cytotoxic, and anti-tumor activities
[31]. Currently, a broad range of biological responses can
be elicited in humans through various terpenoids that are
applicable to human health care [32]. Different terpenoid
molecules have anti-microbial, anti-fungal, anti-parasitic,
anti-viral, anti-allergenic, anti-spasmodic, anti-hyperglyce-
mic, anti-inflammatory, chemotherapeutic, and immuno-
modulatory properties [32, 33]. Terpenes are also used as
skin penetration enhancers, as well as natural insecticides,
and can be of use as protective substances in storing
agriculture products [34].
Resveratrol
Resveratrol is a natural compound made by type of
plants. It is a phyto-alixin, made by plants in stress
conditions and pathogen attack.
Major source
It is found in considerable concentrations in grapes, pea-
nuts, and so forth. In the diet, the major source is found
in red wine (Figure 2). Resveratrol is made in grape skins,
but not in the flesh, thus it is found very little in white
wine, and proportionally in rose wines with the highest
concentration in red wines. The richest natural sources of
resveratrol are dark grape extracts (Vitis vinifera) and
giant knotweed (Polygonnum cuspidatum, a perennial
shrub). It is also found in abundance in labrusca and
muscadine grapes. It is also present in other plants such
as Eucalyptus, spruce, and lily and in foods such as
mulberries, peanuts, blueberries, strawberries, hops,
and their products [35, 36].
Amount
It also occurs in the vines, roots, seeds, and stalks, but
its highest concentration is in the skin, which contains
50–100 µg/g [37].
Mode of action
Resveratrol produces various physiological effects. At low
concentrations that normally occur in food, resveratrol
has been shown to exert neuroprotective effects [38], as
well as beneficial effects on the cardiovascular system
[39]. These effects are mostly attributed to its anti-oxidant
properties. Resveratrol inhibits the proliferation and
induces apoptotic cell death in multiple cancers cell
types in vitro [40, 41]; moreover, in animal models of
cancer, resveratrol has been shown to inhibit
HO
OH
OH
Figure 2 Resveratrol.
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angiogenesis and delay tumor growth [42], impede carci-
nogenesis [43], and reduce experimental metastasis [44].
Resveratrol acts on the process of carcinogenesis by
affecting the three phases: tumor initiation, promotion,
and progression phases, and suppresses the final steps of
carcinogenesis, i.e. angiogenesis and metastasis. It is also
able to activate apoptosis, arrest the cell cycle, or inhibit
kinase pathways.
Therapeutic property
Resveratrol is trans-stilbene that undergoes isomerization
under UV radiation. It is the “trans” form of resveratrol
that has been shown to display a much broader spectrum
of pharmacological activity than its “cis” isomer.
Stilbenes, in particular trans-resveratrol and its gluco-
side, are widely reported to be beneficial to health and
possess anti-oxidative, anti-carcinogenic, and anti-tumor
properties [37]. Trans-resveratrol is synthesized naturally
by several plants in response to pathogen infection, trau-
matic damage, UV irradiation, and other stresses.
Most noticeable biological activities are anti-throm-
bogenic, anti-inflammatory, cardio-protective, neuropro-
tective, anti-aging, and cancer preventive and therapeutic
activities.
Flavonoids
Major source
Flavonoids are polyphenolic compounds present in ber-
ries, legumes, tea, grapes, olive oil, cocoa, walnuts, pea-
nuts, spices, fruits, and vegetables. Green vegetables,
onion, apple, berries, and tea are the rich sources of
flavonoids. Flavonoids are present in most plant tissues
and often in vacuoles [45].
Amount
Flavonols are the most ubiquitous flavonoids in the
foods. Quercetin and kaempfreol are the main represen-
tatives of this group (Figure 3). They are generally present
at relatively low concentrations of about 15–30 mg/kg
fresh weight. Onions, curly kale, leeks, broccoli, and
blueberries are the rich sources of flavonols. Flavanones
are found in tomatoes and certain aromatic plants such
as mint (Mentha piperita), but they are present in high
concentrations only in citrus fruits. The main flavanones
are naringenin in grapefruit, hesperetin in oranges, and
eriodictyol in lemons. The major sources of flavonoids
intake are tea (61%), onions (13%), and apples (10%); the
other sources include cherry, tomato, broccoli, black
grapes, and blueberries [45].
Therapeutic property
Flavonoids have been studied extensively since they have
many curative effects such as anti-bacterial, anti-oxidant,
anti-viral, and analgesic activities [46]. Flavonoids form a
group of many different compounds of which more than
5,000 have been currently characterized. Flavonoids can
be classified into several distinct subclasses based on
their chemical structures and exert various health-
promoting effects in human body for disease prevention.
Among the biological activities, flavonoids are active
against free radicals; free radical mediated cellular sig-
naling, inflammation, allergies, platelet aggregation,
microbes, ulcers, viruses, tumors, and hepatotoxins.
Anti-proliferative effects such as cancers, cardio vascular,
and inflammatory diseases of dietary flavonoids are also
well recognized. Scavenging activity of hydroxyl radicals,
superoxide anion radicals, and lipid peroxy radicals sig-
nifies the health-promoting functions of flavonoids [47].
Mode of action
Flavonoids are a subclass of plant phenols which include
the minor flavonoids (flavanones and dihydroflavonols),
flavones, and flavonols (Table 2). Proposed mechanisms
by which they provide health benefits, in addition to being
direct chemical protectants involve modulatory effects on
a variety of metabolic and signaling enzymes. Flavonoids
R
7
O
O
R
R
2
R
1
R
6
R
7
R
3
R
4
R
5
R
2
R
R
1
R
3
R
4
R
5
R
6
Kaempferol
Quercetin
OH OH
OH OH OH OH
OHOH
OH
H
H
H
HH
HH
Figure 3 Flavonoids.
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have been shown to block the angiotensin converting
enzyme that raises blood pressure; inhibit cyclooxygenase
which forms prostaglandins; and block enzymes that pro-
duce estrogen. The implications of these in vitro inhibitory
actions are that certain flavonoids prevent platelet aggre-
gation, reduce heart disease and thrombosis, and inhibit
estrogen synthase which binds estrogen to receptors in
several tissues, thus decreasing the risk of estrogen-related
cancers. Bioactive properties such as free radical scaven-
ging, inhibition of hydrolytic and oxidative enzymes, anti-
inflammatory and anti-viral [48] action of flavonoids are
well known. There is inverse association between flavo-
noids intake and coronary heart disease mortality.
Flavonoids in regularly consumed foods appeared to
reduce the risk of death from coronary heart disease; but
some flavonoids have been reported to be mutagenic as
well [49]. The capacity of flavonoids to act as anti-oxidants
depends upon their molecular structure. The position of
hydroxyl groups and other features in the chemical struc-
ture of flavonoids are important for their anti-oxidant and
free radical scavenging activities. Quercetin, the most
abundant dietary flavonol, is a potent anti-oxidant
because it has all the right structural features for free
radical scavenging activity [47]. Luteolin has anti-inflam-
matory, anti-mutagenic, and anti-bacterial activities.
Research has proved that apigenin suppressed
Table 2 Dietary sources of polyphenols [109, 110].
Classes/subclasses Polyphenols Sources
Anthocyanidins
Flavonoids
Cyanidin 3-glycosides
Delphinidin
Malvidin
Pelargonidin
Black berries, black currant, black grape, blue berries,
cherries, cranberry, plums, pomegranate, raspberry, red
wine, strawberries
Anthoxanthins
Flavonols
Fisetin
Isorhamnetin
Kaempferol
Myricetin
Quercetin
Apples, apricots, beans, berries, black currant, broccoli,
buckwheat, celery
Cherries, cherry tomatoes, chives, cocoa, grapes, kale,
lettuce, onions
Peppers, plums, red wine, spinach
Sweet potato, tea
Flavanones Hesperetin
Naringenin
Eriodictyol
Citrus fruits and their juices
Grapes, tangerine juice
Flavones Apigenin
Luteolin
Celery, fresh parsley, olives, oregano
Peppers, rosemary
Flavanols
(Flavan-3-ols)
Epicatechin and their gallates, Morin
Procyanidins
Prodelphinidins, Catechin
Apples, apricots, berries, cherries
Chocolate, grapes, peaches, pears, plums, raisins, red
wine, tea
Isoflavones
(Flavans)
Daidzein
Equol, Genistein
Grape seeds/skin, soy cheese and sauces, soy products,
soybean
Flavonoid glycoside Hesperidin
Naringin, Rutin
Grape fruit, lemon, orange juice
Orange, tangerine juice
Phenolic acids Caffeic acid
Chlorogenic acid
Ferulic acid
p-Coumaric acid
Apple, apple juice, blueberry, cider, cranberry, grape fruit,
lemon, lettuce, coffee beans, orange, peach, pear, cherry,
potato, spinach, tea
Hydroxy-benzoic acids Ellagic and Gallic acids Grape juice, pomegranate juice
Raspberry grape juice, longan seed, strawberry
Trihydroxy-stilbenes Resveratrol Grapes, peanuts, red wine
Tannins Catechin
Epicatechin polymers, Ellagitannins
Proanthocyanidins
Tannic acids
Apple juice, blackberry, chick pea
Cocoa, coffee, grape seeds and skin
Lentils, olive, peach, peas, plum
Pomegranate, raspberries, red wine
Strawberries, tea, walnuts
Diferuloylmethane Curcumin Turmeric
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12-O-tetradecanoylphorbol-3-acetate (TPA)-mediated
tumor promotion of mouse skin, similar to curcumin, a
dietary pigmented polyphenol, possibly through suppres-
sion of protein kinase C activity and nuclear oncogene
expression. Apigenin is anti-bacterial, anti-inflammatory,
diuretic, and hypotensive and also promotes smooth mus-
cle relaxation. Myricetin, a hexahydroxyflavone, exhibits
anti-bacterial activity and has anti-gonadotropic activity,
but apparently is not a mutagen. The flavonol kaempferol,
which is widely found in the diet, has anti-inflammatory
and anti-bacterial activities and is directly mutagenic.
Quercetin, the most common flavonoid in higher plants,
seems to contribute to the mutagenicity of kaempferol in
the presence of microsomal metabolizing systems.
Quercetin inhibits a number of enzymes, smooth muscle
contraction, and proliferation of rat lymphocytes.
Although it is anti-inflammatory, anti-bacterial, anti-viral,
and anti-hepatotoxic, it exhibits mutagenic activity and
allergenic properties [50]. Catechins and gallic acids,
major sources of catechins are grapes, berries, cocoa,
and green tea. Tea contains considerable amounts of gallic
acid esters, such as epicatechin, epicatechingallate and
epigallocatechingallate. Numerous studies have suggested
that these components provide protective benefits by their
free radical scavenging ability and their inhibition of eico-
sanoid synthesis and platelet aggregation. The green tea
provides protection against prostate cancer [51]. Wines
contain catechins and procyanidins that are responsible
for its astringency sensation. Catechin is one of the major
phenolics in grapes and red wines and is considered to be
partly responsible for the protective effect against athero-
sclerotic cardiovascular disease.
Isoflavonoids
Major sources
They are another subclass of the phenolic phytonutrients.
Isoflavonoids are produced almost exclusively by the
members of the Fabaceae (Leguminosae) family. Their
main food sources are soy cheese, soy flour, soy bean,
and tofu. Soybeans are an unusually concentrated source
of isoflavones, including genistein and daidzein (Figure 4),
and soy is the major source of dietary isoflavones.
Therapeutic property
The isoflavones of soy have a property of binding to the
estrogen receptor class of compounds, thus representing
an activity of a number of phytochemicals termed phy-
toestrogens. Genistein inhibits the growth of most hor-
mone-dependent and -independent cancer cells in vitro,
including colonic cancer cells. Isoflavones have received
considerable attention as potentially preventing and
treating cancer and osteoporosis [52]. Research in mice
has shown that dietary soybean components inhibited
the growth of experimental prostate cancer and altered
tumor biomarkers associated with angiogenesis.
Although the epidemiological data suggest that soy
potentially decreases the risk of breast and prostate can-
cer but the evidence that soy exerts a protective effect
against colonic cancer is limited.
Mode of action
Anti-oxidant and anti-proliferative properties of isoflavones
offer important mechanisms for their protection against
many prevalent chronic diseases [53, 54]. Cellular damage
resulting from oxidative stress is believed to be a major
contributor to the etiology of cardiovascular disease
through the oxidation of LDL and cancer by causing DNA
strand breaks which may lead to mutations [55, 56]. Recent
research has shown that the isoflavone genistein from soy,
selectively bound to the β-estrogen receptor and reduced
binding to the α-receptor 20-fold.
Carotenoids
Major sources
The group of carotenoids consists of more than 700 phy-
tochemicals, which constitute photosynthetic membranes
O
HO
O
R
2
R
1
R
1
= H, R
2
= OMe (Formononetin)
R
1
= OH, R
2
= OMe (Biochanin A)
R
1
= H, R
2
= OH (Daidzein)
R
1
= OH, R
2
= OH (Genistein)
Figure 4 Isoflavones (phytoestrogen).
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and produce colors in plants and animals. Out of 700
pigments, only about 24 commonly occur in human food-
stuffs [57]. The most studied carotenoids are α-carotene,
β-carotene, lycopene, lutein, and zeaxanthin (Figure 5).
The principal carotenoids of foods are β-carotene, β-cryp-
toxanthin, lycopene, and lutein. Carotenoid pigments are
abundant in many fruits and vegetables and have been
studied for their diverse roles in phytochemistry and
phytomedicine [57].
Carotenoids are mainly C
40
isoprenoids, consisting
of eight isoprene units. There are two main groups of
carotenoids (i) carotenes (β-carotene, lycopene) contain
only hydrogen and carbon and may be cyclic or linear;
(ii) oxycarotenoids (xanthophylls, lutein) contain hydro-
gen, carbon, and oxygen in the form of hydroxy, epoxy,
and oxy groups, respectively. The polyene chain in car-
otenoids contains upto 15 conjugated double bonds,
which are responsible for their characteristic absorption
spectra and specific photochemical properties [58]. They
are responsible for quenching singlet oxygen and for
intercepting deleterious free radicals and ROS. These
properties make them a part in diverse anti-oxidant
defense system. Most carotenoids are found in linear or
all trans-configuration. However on exposure to light or
heat facilitates their inter-conversion from “trans” to “cis”
isomerization of one or more double bonds [59].
The physico-chemical properties and the biological activ-
ities of carotenoids are intimately related to their chemi-
cal structures. Epidemiological studies have shown a
positive link between higher dietary intake and tissue
concentrations of carotenoids with lower risk of chronic
diseases [60, 61].
Therapeutic property
The β-carotene and lycopene have been shown to be
inversely related to the risk of cardiovascular diseases
and certain cancers, whereas lutein and zeaxanthin are
related with the prevention of eye disorders [60, 62].
Lutein protects against uterine, prostate, breast, color-
ectal, and lung cancers. They also protect against risk
of digestive tract cancer. Xanthophyll, a type of carote-
noids, offers protection to other anti-oxidants and exhibit
tissue specific protection. Zeaxanthin, cryptoxanthin, and
astaxanthin are all the members of xanthophyll group
[63, 64].
Mode of action
The anti-oxidant properties of carotenoids have been sug-
gested to be the main mechanism by which they afford their
beneficial effects. Research has shown that carotenoids med-
iate their effects through other mechanisms such as gap
junction communication, cell growth regulation, modulat-
ing gene expression, immune response, and modulators of
Phase I and II drug metabolizing enzymes [65, 66].
Lycopene
Major source
Lycopene, a carotenoid without provitamin-A activity, is
present in many fruits and vegetables (Figure 6);
CH
3
CH
3
CH
3
CH
3
CH
3
H
3
C
H
3
C
CH
3
CH
3
H
3
C
Figure 5 β-Carotene.
CH
3
CH
3
CH
3
CH
3
CH
3
H
3
C
H
3
C
CH
3
HO
H
3
CCH
3
OH
Figure 6 Lycopene.
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however, tomatoes and processed tomato products con-
stitute the major source of lycopene in diet. Among the
carotenoids, lycopene is a major component found in the
serum and other tissues.
Therapeutic property
Dietary intakes of tomatoes and tomato products contain-
ing lycopene have been shown to be associated with
decreased risk of chronic diseases such as cancer and
cardiovascular diseases. Serum and tissue lycopene
levels have also been inversely related with the chronic
disease risk. Although the anti-oxidant properties of lyco-
pene are primarily responsible for its beneficial proper-
ties, other mechanisms such as modulation of
intercellular gap junction communication, hormonal
and immune system, and metabolic pathways are also
involved [67].
Mode of action
Lycopene also has the ability to destroy free radicals that
are produced as a result of metabolic reactions in the
body. It suppresses the attack of cellular oxygen and
ROS thereby slowing down the formation of free radicals
and therefore prevents destruction of the lipophilic parts
of the cell [68].
A study assessing the acute effects of lycopene on
airway hyper-responsiveness was carried out in patients
with exercise-induced asthma (EIA). The results showed
that 55% of those taking lycopene were significantly
protected against EIA and did not experience this inhaled
steroid dose FEV1 reduction [69]. The anti-oxidant capa-
city of lycopene offers protection against γ-radiation
induced damage to cells [70].
A study by Gitenay et al. [71] showed that even yellow
varieties of tomatoes that are without lycopene showed a
stronger anti-oxidant effect in rats. Rats with mild oxida-
tive stress, caused by low vitamin E level, were fed with
placebo, yellow tomato extract, red tomato extract, and
lycopene. All diets had no effect on plasma cholesterol
but only the red tomato diet reduced triglycerides. Rats
fed with yellow or red tomato extract showed lower levels
of thiobarbituric reactive species in the heart than those
fed with placebo or lycopene. This led the researchers to
conclude that tomatoes, containing lycopene or not, have
a higher potential than lycopene alone to attenuate
oxidative stress parameters in a mild oxidative stress
context [71].
Limonoids
Major sources
These are terpenes present in citrus fruit. Citrus limo-
noids are present in large amounts in citrus juice and
citrus tissues as water-soluble limonoid glucosides or in
seeds as water-insoluble limonoid aglycones [72].
Therapeutic property
Limonoids are highly oxygenated triterpenoid com-
pounds with significant biological activity.
Mode of action
Several citrus limonoids are studied for their role as anti-
cancer utilizing laboratory animals and human breast
cancer cell cultures. In mice, it was found that five limo-
noid aglycones (limonin, nomilin, obacunone, iso-obacu-
noic acid, and ichangin) induced significant amounts of
glutathione-S-transferase (GST) in the liver and intestinal
mucosa [73]. GST is a major detoxifying enzyme system
that catalyzes the conjugation of glutathione with many
potentially carcinogenic compounds which are highly
electrophilic in nature. A study of the inhibitory effects
of two limonoid aglycones (limonin and nomilin) on the
formation of benzo[a]pyrene induced neoplasia in the
fore stomach of ICR/Ha mice showed that incidence of
tumors could be reduced by more than 50% at 10 mg/
dose [74]. The experimental results described above indi-
cate that citrus limonoids may provide substantial anti-
cancer actions. The compounds have been shown to be
free of toxic effects in animal models so limonoids has a
potential against human cancer in either the natural
fruit or in citrus fruits fortified with limonoids, or in
purified forms of specific limonoids. They provide che-
motherapeutic activity by inhibiting Phase I enzymes and
inducing Phase II detoxification enzymes in the liver.
D-Limonene, a common monocyclic monoterpene,
found within orange peel oil, inhibits pancreatic carcino-
genesis induced in experimental models and also pro-
vides protection to lung tissue [63, 64]. Although the
initial studies are very promising, they have been con-
ducted primarily with in vitro cell culture and animal
models. Thus, more research is needed to determine
whether limonoids may be useful in preventing or treat-
ing cancer in humans. The first step is to assess the
bioavailability of the compounds for humans, their
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absorption after ingestion, and appearance in the blood
and tissues. If limonoid compounds are found to be
bioavailable, then more human studies are needed to
assess the effects of limonoid ingestion on biomarkers
related to cancer [64].
Phytosterols
Major source
These are another important terpene subclass. The primary
sources of phytosterols are vegetables, nuts, fruits, and seeds.
Amount
Seeds contain an average of 120 mg of plant sterols/100 g
wet weight; vegetables contain 20 mg/100 g of wet
weight and fruit about 15 mg/100 g wet weight.
Sitosterol, campesterol, and stigmasterol are most abun-
dant in nature comprising 65%, 30%, and 3% of dietary
phytosterol intake (Figure 7) [75].
Therapeutic property
The two sterol molecules synthesized by plants are
β-sitosterol and its glycoside. In animals, these two mole-
cules exhibit anti-inflammatory, anti-neoplastic, anti-
pyretic, and immuno-modulating activity.
Mode of action
Phytosterols block inflammatory enzymes by modifying the
prostaglandin pathways in a way that protect platelets.
Phytosterols compete with cholesterol in the intestine for
uptake and aid in the elimination of cholesterol from the
body. Plant sterols are initially solubilized into a micelle
form in the intestine. These micelles interact with brush
border cells and are transferred into enterocytes. Plant ster-
ols are esterified within the enterocyte, assembled into
chylomicrons, and secreted into the lymphatics. They are
excreted through the biliary system. The non-esterified phy-
tosterols are transported back into the intestinal lumen by
sterolin (1 and 2) pumps containing the ATP binding cas-
sette (ABC) proteins encoded by the genes ABCG5 and
ABCG8. These are expressed in the mucosal cells and the
canalicular membrane, and they re-secrete sterols, espe-
cially absorbed plant sterols, back into the intestinal
lumen and from the liver into bile [76]. Saturated phytoster-
ols appear to be more effective than unsaturated com-
pounds in decreasing cholesterol concentrations in the
body. Their actions reduce serum or plasma total choles-
terol and LDL cholesterol. There is a competition between
phytosterol and cholesterol for absorption from the intes-
tine due to their structural similarity. In mammals, concen-
trations of plasma phytosterol are low because of their poor
absorption from the intestine, their faster excretion from
liver and metabolism to bile acids, compared with choles-
terol [77]. Animal studies have shown that phytosterols
reduce atherosclerosis in the Apo-E deficient mouse
model. Mixed results were obtained from the human studies
and these studies do not prove or disprove an increase in
atherosclerotic risk that can be clearly related to serum
phytosterol levels. Studies have proved that vegetarians
who consume considerable plant sterols are at decreased
risk of arteriosclerosis cardiovascular disease [75].
Phytoestrogens
Major source
Phytoestrogens are non-steroidal compounds produced
by plants and present in many natural dietary products,
such as soybeans, wheat, barley, corn, alfalfa, and oats.
They occur in either plants or their seeds. There are
several classes of phytoestrogens: steroidal estrogens,
found in few plants and the more ubiquitous are phenolic
estrogens, isoflavones, stilbenes, coumestans, and lig-
nans. Soybean is rich in isoflavones, whereas the soy
sprout is a potent source of coumestrol, the major coume-
stan. The precursors of these substances are widespread
in the plant kingdom, but mainly found in Leguminosae
and are especially abundant in soybean and its products,
legumes, berries, whole grains, and cereals [7].
Brassicasterol
Sitosterol Sti
g
masterol
HOHO
HO
HO
Campesterol
Figure 7 Phytosterols.
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The main dietary sources of coumestans are sprouted
legumes such as soy and alfalfa; however, low levels
have been reported in brussel sprouts and spinach.
Clover and soybean sprouts are reported to have its high-
est concentrations. The phytolignans are found in high
amounts in flaxseed, asparagus, whole grains, vegeta-
bles, and tea. Fruits also have their low levels with the
exception of strawberries and cranberries [7].
Mode of action
These are non-steroidal phytochemicals quite similar in
structure and function to gonadal estrogen hormone.
They offer an attractive alternate for HRT with beneficial
effects on cardiovascular system and may even alleviate
menopausal symptoms. They are potential alternatives to
the synthetic selective estrogen receptor modulators,
which are currently applied in HRT. They have anti-oxi-
dant effects due to their polyphenolic nature, anti-carcino-
genic, modulation of steroid metabolism or of
detoxification enzymes, interference with calcium-trans-
port, and favorable effects on lipid and lipoprotein profiles
[7, 78]. On the basis of chemical structure phytoestrogens
can be classified as isoflavones, flavones, coumestans,
stilbenes lignans, and coumestans (Figure 4).
Therapeutic property
Flavonoids have similar structure to estrogen, have the
capacity to exert both estrogenic and anti-estrogenic
effects, and provide possible protection against bone
loss and heart diseases. They share structural features
with estrogen, in the sense that the presence of particular
hydroxyl groups can be positioned in a stereo chemical
alignment virtually identical to one of the estrogens.
Populations in China, Japan, Taiwan, and Korea are esti-
mated to consume high quantities of isoflavones, and
women of these countries complain fewer incidences of
osteoporosis and related health problems, especially hot
flushes and cardiovascular diseases and lower incidence
of hormone-dependent breast and uterine cancers
[79–81]. The main dietary source of phytoestrogenic stil-
benes is resveratrol from red wine and peanuts. Although
there are two isomers of resveratrol, “cis” and “trans”,
but only the “trans” form has been reported to be estro-
genic. It is found only in the skin of red grapes and green
grapes whereas white wine contains very low levels of
trans-resveratrol [82]. The term lignan is used for a
diverse class of phenylpropanoid dimers and oligomers.
Secoisolariciresinol and matairesinol are two lignan
dimers which are not estrogenic by themselves, but read-
ily convert to the mammalian lignans, enterodiol and
enterolactone, respectively, which are estrogenic. These
are of great interest because of their estrogenic, anti-
carcinogenic, anti-viral, anti-fungal, and anti-oxidant
activities [83].
In humans, gut microflora enzymatically metabolizes
the isoflavones and lignans, and the mammalian lignans
are readily absorbed [84]. The different activities and the
bioavailability of phytoestrogens vary depending on fac-
tors such as the form of administration, dosage, individual
metabolism, and the ingestion of other pharmacological
substances [85].
Glucosinolates
Major sources
GLSs are exclusively found in dicotyledonous plants,
genus Brassica alone contains more than 350 genera
and 3,000 species [86]. Crucifers contain very high con-
centration of GLSs. Many commonly consumed vegeta-
bles, condiments, forages and oil containing plants, such
as cabbage, broccoli, cauliflower, collards, kale, mustard,
brussels sprouts, and rapeseeds are good sources of GLSs
[87]. These vegetables are an excellent dietary source of
phytochemicals including GLSs and its breakdown pro-
ducts, phenolics and other anti-oxidants like vitamins C
and K, as well as dietary essential minerals [88].
Therapeutic property
They are present in cruciferous vegetables and are activa-
tors of liver detoxification enzymes. These chemicals are
responsible for the pungent aroma and bitter flavor of
cruciferous vegetables. Consumption of cruciferous vege-
tables provides protection against carcinogenesis, muta-
genesis, and other forms of toxicity of electrophiles and
reactive forms of oxygen. The sprouts of certain crucifers,
including broccoli and cauliflower, contain higher
amounts of glucoraphanin (the GLS of sulforaphane)
than do the corresponding mature plants. Crucifer sprouts
may protect against the risk of cancer more effectively than
the same quantity of mature vegetables of the same variety
[89, 90]. During food preparation, chewing, and digestion,
GLSs in cruciferous vegetables are broken down to form
biologically active compounds such as indoles, nitriles,
thiocyanates, and isothiocyanates [91]. Indole-3-carbinol
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(an indole) and sulforaphane (an isothiocyanate) have
been scientifically proved for their anti-cancer effects.
Epidemiological studies indicate that consumption of bras-
sica vegetables is associated with a reduced incidence of
cancers at a number of sites including the lung, stomach,
colon, and rectum due to the presence of a predominating
thioglucosides GLSs, [92] (Figure 8).
Mode of action
Dietary GLSs block the formation of endogenous or exo-
genous carcinogens that prevent the initiation of carcino-
genesis [93]. The mechanism of protective effect is due to
the modulation of carcinogen metabolism by the induc-
tion of Phase II detoxification enzymes and inhibition of
Phase I carcinogen-activating enzymes, thereby influen-
cing several processes related to chemical carcinogenesis,
e.g. the metabolism, DNA binding, and mutagenic activ-
ity of promutagens. Studies in experimental animals
including humans have proved a reducing effect on
tumor formation and positive effect on health on con-
sumption of adequate amounts of indoles in brassica
vegetables. Indole-3-carbinol is a GLS metabolite that
inhibits organ-site carcinogenesis in rodent models. Its
preventive effect on human mammary carcinogenesis is
due to its ability to regulate cell cycle progression,
increase the formation of anti-proliferative estradiol
metabolite, and induce cellular apoptosis [89, 90].
ω-3 fatty acids
There is an extensive interest in increasing consumption of ω-
3 fatty acids, because they are associated with many health
benefits, but are consumed only in small amounts. In 2002,
the National Academy of Sciences Institute of Medicine
recognized that ω-3 fatty acids are essential in the diet and
established an estimated adequate intake for them [94].
Major source
The main food sources of the long-chain ω -3 fatty acids
are fish, especially fatty species such as salmon, rainbow
trout, mackerel, herring, and sardines. Plants like canola,
soybean, and flax oils provide the 18-carbon ω-3 fatty
acid, α-linolenic acid (Figure 9). However, higher plants
lack the enzymes to make 20- and 22-carbon polyunsatu-
rated fatty acids (PUFAs) needed by mammals. Humans
can convert α-linolenic acid to the more biologically
active long-chain form but not so efficiently. Thus, plant
foods with α-linolenic acid may be insufficient to supply
the need for long-chain ω-3 fatty acids, especially during
pregnancy and lactation [95].
Therapeutic property
The benefit of ω-3 fatty acids is well known in the treat-
ment of people suffering from osteoarthritis. Clinical stu-
dies have proved the value of ω-3 fatty acids in treating
inflammatory conditions ranging from atherosclerosis to
osteoarthritis. People suffering from osteoarthritis can
improve symptoms and even allow a reduction in the
use of NSAIDs on increasing their dietary intake of ω-3
fatty acids and monounsaturated fatty acids as found in
olive oil [96]. These fatty acids have other positive effects
like influencing cellular metabolic functions, supporting
cell membrane structure, and reducing the expression of
pro-inflammatory cytokines [97]. The most potent of the
ω-3 fatty acids containing oils are eicosapentaenoic acid
(EPA) and docosahexaenoic acid, which are found in
abundance in cold-water fish [98].
Western diets contain predominately ω-6 PUFAs
found in soybean, corn, sunflower, canola, and cotton-
seed oils. It is now recognized that diets high in ω-6 fatty
acids and low in ω-3 fatty acids may exacerbate several
chronic diseases [99]. One strategy to increase the avail-
ability of long-chain ω-3 fatty acids is to develop oilseed
RC
S b-D-glucose
N
OSO
3
-
Figure 8 General structure of GLS.
12
b
a
1215
9
9
1
1
C
C
O
O
OH
OH
9
Figure 9 (a) α-Linolenic acid and (b) structure linoleic acid.
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crops such as canola and soybean that contain stearido-
nic acid (18:4n-3). This ω-3 fatty acid occurs naturally in
only a few plants such as black currant seed oil and
echium. Stearidonic acid is the first product formed
when α-linolenic acid is converted to EPA, a desirable
long-chain ω-3 fatty acid.
Anthocyanins
Major source
Anthocyanins occur in all tissues of higher plants, includ-
ing leaves, stems, roots, flowers, and fruits.
Anthocyanins are derivatives of anthocyanidins, which
include pendant sugars (Figure 10). Plants rich in antho-
cyanins are Vaccinium species, such as blueberry, cran-
berry, blackberry, cherry, and red cabbage. The highest
recorded amount appears to be especially in the seed
coat of black soybean [100].
Therapeutic property
Anthocyanins are the largest group of water-soluble pig-
ments in the plant kingdom. They have potential health
benefits and disease prevention properties and are
known as potential anti-oxidants [101]. Consumption of
anthocyanin-enriched foods is associated with a reduced
risk of several diseases such as atherosclerosis [102],
dyslipidemia [103], and diabetes [104]. Anthocyanins
may appear red, purple, or blue depending on the pH.
They are synthesized through the phenylpropanoid path-
way; they are odorless and nearly flavorless, contributing
to taste as a moderately astringent sensation.
Anthocyanins are secondary metabolites and are also
approved for use as a food additive in the European
Union, Australia, and New Zealand. The main anthocya-
nin compounds are pelargonidin, cyaniding, and delphi-
nidin. Cyanidin and its glycosides are naturally dietary
pigments which have been found with promising poten-
tial benefits to humans, especially in the prevention and
treatment of diabetes mellitus [104, 105].
Probiotics – the unconventional source of
bioactive food components
The probiotics are the unconventional source of bioactive
food components. The combination of probiotics and
prebiotics commonly known as synbiotics modifies the
composition of the GI microbiota, restores the microbial
balance, and therefore has the potential to provide health
benefits [106, 107].
Major source
The majority of probiotic microorganisms belonging to the
genera Lactobacillus and Bifidobacterium are present in
abundance in fermented dairy products like yoghurt, fer-
mented milk, and butter-milk. Both Lactobacillus and
Bifidobacterium are Gram-positive lactic acid-producing
bacteria that constitute a major part of the normal intest-
inal microflora in animals and humans [108]. The number
of Bifidobacteria in the colon of adults is 10
10
–10
11
CFU/g,
but this number decreases with age. Bifidobacteria are non-
motile, non-spore forming, Gram-positive rods with varying
cell morphology. Most strains are strictly anaerobic.
Prebiotics and lactic acid bacteria (LAB) (probiotics)
have demonstrated beneficial effects with respect to the
function of innate immunity, intestinal barrier function,
and increased resistance to disease. The gut mucosa and
microbiota are intimately linked in the maintenance of a
functional interface between the host and the external
environment [109, 110]. A combined supply of prebiotics
and probiotics (synbiotics) has synergistic effects in enhan-
cing immunity and facilitating intestinal barrier function.
Therapeutic property
The probiotic bacteria are used for the manufacture of a
natural remedy, for controlling weight gain, preventing
obesity, increasing satiety, prolonging satiation, reducing
food intake, reducing fat deposition, improving energy
R
2
R
7
O
+
R
3
R
4
R
5
R
6
R
R
1
R
7
R
2
R
R
1
R
3
R
4
R
5
R
6
Pelargonidin
Cyanidin
OH OH H OHOH H OH H
Delphinidin
OH OH OHOHHHHH
OH OH OHOH
HOH H
OH
Figure 10 Anthocyanins.
164 Gupta and Prakash: Bioactive compounds in health
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metabolism, treating and enhancing insulin sensitivity,
and treating obesity. Animal studies have demonstrated
the efficacy of some strains of LAB to lower serum cho-
lesterol levels, presumably by breaking down bile in the
gut, thus inhibiting its re-absorption [111].
Lactobacillus (Lb. sporogenes and Lb. acidophilus
NCFB 1748) and Bifidobacterium genus representatives
have been reported to play a critical role in weight reg-
ulation as an anti-obesity effect in experimental models
and humans [112]. Lactobacillus sporogenes has the abil-
ity to lower cholesterol levels. It produces a significant
reduction in LDL levels and a small but significant
increase in high-density lipoprotein cholesterol.
Lactobacillus acidophilus ferments lactose into lactic
acid, like many LAB. During digestion, L. acidophilus
assists in the production of niacin, folic acid, and pyri-
doxine. It also helps in bile de-conjugation, separating
amino acids from bile acids, which can then be recycled
by the body [113]. L. acidophilus may provide additional
health benefits, including improved gastrointestinal func-
tion, a boosted immune system, and a decrease in the
frequency of vaginal yeast infections and relief from indi-
gestion and diarrhea [114]. In addition, probiotics, pre-
biotics, and synbiotics are frequently recommended after
a course of antibiotics as a means of restoring the micro-
biota within the intestinal tract to its normal, healthy
state, as well as an aid in resolving uncomplicated
cases of diarrhea. Synbiotics are also being investigated
as aids in treating some non-gastrointestinal diseases.
There is some evidence that synbiotics may be useful in
treating some skin ailments, such as atopy.
Mode of action
Intake of probiotics, prebiotics, and synbiotics has been
demonstrated to modify the composition of the GI micro-
biota, restore the microbial balance, and therefore, have the
potential to provide health benefits. However, only recently,
well-designed clinical studies have provided clear evidence
of health-promoting effects, such as prevention of antibiotic-
associated diarrhea, treatment of acute diarrhea, inflamma-
toryboweldisease,eradicationofClostridium difficile infec-
tion, and enhancement of intestinal immunity [115, 116].
Market trend of phytonutrients
The markets for phytonutrients in the form of nutraceu-
ticals and functional foods are rapidly expanding. They
represent annual global sales of US$75 billion in 2007. It
is reported that the Global Nutraceutical market would
grow at a CAGR of 6.30% over the period of 2013–2018.
One of the key factors contributing to this market growth
is the increasing global aging population. The Global
Nutraceutical market has also been witnessing the
increase in the nutraceutical product development.
However, the threats of ingredients and raw material
contamination could pose a challenge to the growth of
this market [117].
The predicted annual growth rates of various nutra-
ceutical categories have been estimated to range from 6%
for products treating digestive ailments up to 25% for eye
health products.
Current and predicted sales claim that the joint
health supplements like glucosamine, chondroitin, and
MSM appear to be the major product group, followed by
the PUFAs. However, fish oils and MSM have been pre-
dicted to show the greatest increase in sales [118]. The
contemporary use of soy, for example, is not simply a
matter of geographical habitat or cultural lifestyle. The
availability of specific foods and nutraceuticals refined
from soy allows all consumers to derive the proposed
benefits. This also applies to green tea, fish oils, flaxseed,
and others. However, a more active approach has to be
taken with those only normally available in formulated
dosages such as glucosamine, chondroitin, and MSM, for
example.
Nutraceutical manufacturers are extolling the virtues
of controlled release formulations for release of precise
levels of active entities over a particular time period, in
order to achieve maximum therapeutic effects. An exam-
ple of the use of this technology is the Novasoy soya
isoflavone range [119].
Conclusions
The present paper thus provides a comprehensive insight
into some of the major phytonutrients of therapeutic
importance, their human health benefits, and their pos-
sible use as health supplements and nutraceuticals.
Dietary intake of phytochemicals promotes health bene-
fits by protecting against chronic degenerative disorders,
such as cancer, cardiovascular, and neurodegenerative
diseases. These phytochemicals, either alone and/or in
combination, have tremendous therapeutic potential in
curing various ailments. Phytochemicals with nutraceuti-
cal properties present in food are of enormous signifi-
cance due to their beneficial effects on human health
Gupta and Prakash: Bioactive compounds in health 165
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since they offer protection against numerous diseases or
disorders such as cancers, coronary heart disease, dia-
betes, high blood pressure, inflammation, microbial, viral
and parasitic infections, psychotic diseases, spasmodic
conditions, and ulcers. Thus phytonutrients can be reg-
ularly taken without any side effects. The future of nutra-
ceuticals from both plant (phytonutrients) and animal
origin holds exciting opportunities for the food industry
to create novel food products containing bioactive food
components. The government should persuade the food
industry by investing more in the nutraceuticals and
functional foods and gaining monetary rewards.
However, the products should be designed and formu-
lated as per the interest and tastes of the consumers.
Acknowledgments: Authors are grateful to Dr Ashok K.
Chauhan, Chairman and Founder President and Mr Atul
Chauhan, Chancellor, Amity University-UP, Noida-
201303, (India) for the encouragement, research facilities,
and financial support.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors sta-
ted that there are no conflicts of interest regarding the
publication of this article. Research support played no
role in the study design; in the collection, analysis, and
interpretation of data; in the writing of the report; or in
the decision to submit the report for publication.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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Useful links and database
http://www.cabi.org/nutrition/ebook/20143083504
http://www.academicpub.org/jmrd/paperInfo.aspx?ID=20
http://link.springer.com/chapter/10.1007/978-1-60761-308-
4_12#page-1
Gupta and Prakash: Bioactive compounds in health 169
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