Polyphenols More Than An Antioxidant Role and Scop
Polyphenols More Than An Antioxidant Role and Scop
Abstract
In this article, an attempt has been made review on phenolics antioxidant activity, and characteristics,
as well as the constituents of the different phenolics present in various consumable food items, which
reduce the risk of non-communicable diseases. Some polyphenolic compounds are present in
selected species, which are beneficial to public health, and it should be comprised as component
of food habits for a proper nutrition’s plan. Polyphenols are basically a natural compound and their
micronutrients are found in different fruits, beverages, and vegetables. There is no specific deficiency
disease caused due to the low dietary intake of phenolics; while the proper intake possibly gives
health benefits. Polyphenols are antioxidants, and evidence for their role with improved heart health,
neurodegenerative (Alzheimer’s disease) diseases, better blood sugar control, diabetes, reduced
inflammation, and a reduced risk of cancer development was studied. A comprehensive understanding
of the biological availability of the nutritional polyphenols will helpful to recognize those that are
beneficial and protective for human health. Based on latest reports, polyphenolic compounds
occupy a unique place in environmental science as an important and common class of bioactive
natural products globally. It is building a bridge between different interdisciplinary academic fields
of science. This work is based on the reports examined the health effect of polyphenols until today.
Keywords: Phytochemicals, antioxidants, polyphenols, Food sources, Dietary intake, Non-Communicable Diseases,
Bioavailability
Citation: Syed Khalid Mustafa, Atif Abdul Wahab A. Oyouni, Meshari M. H. Aljohani and M. Ayaz Ahmad, Polyphenols more than
an Antioxidant: Role and Scope, J. Pure Appl. Microbiol., 2020; 14(1): 47-61. https://doi.org/10.22207/JPAM.14.1.08
© The Author(s) 2020. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License which
permits unrestricted use, sharing, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and
the source, provide a link to the Creative Commons license, and indicate if changes were made.
heterocyclic (ring C), further subdivided as have been identified. Polyphenols are found in
flavonols, flavones, isoflavones, flavanones, high amount mainly, in coffee, berries, and dark
anthocyanidins, and flavanols (catechins and chocolate, cocoa powder, olive oil, in certain spices
proanthocyanidins). Flavonoids and phenolic acids and seasonings, like cloves and star anise. Some of
are the most common classes. the top sources of polyphenol foods that should
Flavonoids or bioflavonoids are classified be added in daily diet intake have been shown in
as plant and fungi secondary metabolites. Table 1.
Flavonoids have the common arrangements with Olive Oil
a 15-carbon atoms which contains two benzene The least processed form of olive
rings (A and B) and a heterocyclic ring (C), depicted oil is called Extra-virgin olive oil; it has the
in Fig. 5. dense collection of polyphenolic compounds,
Stilbene extracted from the olive fruit. Consuming
1, 2-diphenylethene {structural formula of olive oil as a diet inappropriate quantity
C6H5CH=CHC6H5} exist in the cis and trans form. helps to protect from heart disease, strokes,
Classified as a diarylethene, it has a central metabolic syndrome, and some kinds of cancer
ethylene group attached with one phenyl group diseases.19,20.
substituents on each end of the carbon-carbon Health Effect of Polyphenols
double bond (Fig. 6). There is no doubt that food can act
Lignans as natural medicine, our diet can determine
The lignans are a large collection of our destiny and fate. Polyphenols including
polyphenols present in plant life. Flaxseed and flavonoids, tannins, lignans, and stilbenes are
sesame are the best sources of lignans than the most abundant phytochemicals in our diet.
most other foods. Fundamentally the chemical Polyphenol-rich foods found in fruits, vegetables,
structures of lignans have two phenyl propane nuts, and seeds are medicine to enhance our
groups attached to a C-C bond connecting the health quality and life span. The modes of action
central atoms of the particular side chains of different polyphenolic compounds, more than
(position 8 or β), also named β-β’ bond, as it has ever as correlated to reduced menace of disease
been illustrated in Fig. 714-15,18. in individuals, are not entirely explained. A number
Leading Food sources with Polyphenols of show antioxidant behaviors, while others
More than 8,000 types of polyphenols activate defense mechanisms that improve the
Journal of Pure and Applied Microbiology 50 www.microbiologyjournal.org
Table 1. Daily diet intake of polyphenols in various food items
Grains Nuts Beans Vegetables Beverages Fruits Others
51
spinach, vinegar grapes, dried marjoram,
shallots grapefruit, dried parsley,
nectarines, dried peppermint,
peaches, dried spearmint,
pears, lemon, verbena,
pomegranate, Mexican, oregano,
plums, Rosemary,
raspberries, Sage,
Strawberries Star anise
Mustafa et al., J. Pure Appl. Microbiol., 14(1), 47-61 | March 2020 | https://doi.org/10.22207/JPAM.14.1.08
www.microbiologyjournal.org
Mustafa et al., J. Pure Appl. Microbiol., 14(1), 47-61 | March 2020 | https://doi.org/10.22207/JPAM.14.1.08
response to oxidative stress and preventing from cherries, cantaloupe, grapes, plums, and pears are
extensive damage. They have been associated with all rich in polyphenols. In addition, vegetables such
numerous valuable effects on human being health. as parsley, broccoli, celery, cabbage, and onion,
Currently, many researchers have taken an interest green tea, white tea, black tea, chocolate, as well
in polyphenols, because of their antioxidant as olive oil, are rich in polyphenols16-21.
nature, large quantity in our food, and their action Polyphenols as an Antioxidant
in the prevention of different diseases related to Compounds that repress oxidation
oxidative stress, such as cancer, cardiovascular and are called antioxidants. Oxidation is a chemical
neurodegenerative diseases. Intake of polyphenols process that is able to generate free radicals.
can be achieved by consuming a large variety of Atom or group of atoms that has an unpaired
plant foodstuff because the main resource of electron called free radicals. They are generally
polyphenols is dietary. This dietary polyphenol unstable and very reactive for the reason that
includes honey, most legumes and fruits are all rich unpaired electrons are likely to form pairs with
in polyphenols. Meanwhile, fruits such as apples, other electrons. When the metabolism taking
pomegranate, strawberries, blackberries, Aronia place in a living organism: an oxygen molecule
berries, cranberries, blueberries, raspberries, (O2) undergoes four-electron reduction. Reactive
oxygen metabolites are generated in this process, (PhOH) is based on the contribution of an H-atom,
maybe due to the excitation of electrons, the which disrupts and terminates the succession
addition of energy or interaction with transition reactions initiated by the free radicals in the living
elements. These generated reactive oxygen organism.
metabolites are extremely reactive than the R• + PhOH ̶ ̶ ̶ > R- H + PhO•
oxygen molecule, are called active oxygen species. The generated phenoxyl radicals (PhO•)
Superoxide (O 2-), hydrogen peroxide (H 2O 2), maybe stabilized through the resonance or by
hydroxyl radicals (OH*), and singlet oxygen (1O2) the self-combination of (PhO•) to yield dimer
is the example of active oxygen species. In living products, and finally terminating the chain
cells, the formations of free radicals are taking reaction.
place mainly due to the homolytic chemical bond PhO• + PhO• ̶ ̶ ̶ >PhO-OPh
fission, photolysis, and radiolysis, and due to More than 8,000 types of natural
red-ox reactions. The free radicals are initiating polyphenols have been identified. Meanwhile,
the chain reaction in the living organism, which polyphenols are made up of multiple phenol units
may lead to cell damage, thus inducing various and are found naturally in many dietary sources,
diseases. Antioxidants are such substances that associated with many health benefits due to their
terminate the chain reaction, initiated by the free antioxidant content21-28.
radicals in the living organism. In other words, Anticancer effects and Polyphenols
antioxidants neutralize or deactivate the action of Cancer treatment and cancer prevention
reactive oxygen species (free radicals), and protect is a big challenge for the whole scientific
the living organism from the harmful consequence community. According to WHO January 2019
of the free radicals. The difference between the reports cancer is the next most important reason
formation of highly reactive oxygen groups (free of death internationally and is likely to account
radicals) and antioxidant defenses, called Oxidative for 9.6 million deaths in 2018. In other words,
stress. Produced free radical species attack the approximately one in six deaths due to cancer
existing pro-oxidants (molecules or ions) because reported internationally. About 30-50% of all
it has a very high affinity to combine with others. cancer cases are possibly preventable. A balanced
The human body depends on various endogenous diet, to get the proper nutrition is a better strategy
resistance mechanisms to defend against free in prevention more than in cancer therapy. Dietary
radical-induced cell injure. Impair of the body cells adaptation and alteration are an important
due to reactive oxygen species (free radicals) plays approach to cancer control. Consumption of fruits
a significant character in the aging development, and vegetables may have an impressive defensive
and in disease growth or development. outcome against several cancers such as the
It has been recommended that an oesophagus, colorectal, breast, endometrium, and
insufficient nutritional consumption of a nutrient kidney. Healthy eating is a way of life that helps
may be compromised with the efficiency of to check the development of diet-related cancers
these antioxidant resistance mechanisms. Many will also decreases the probability of other non-
daily practices are directly related to oxidative communicable diseases [NCDs]29.
stress, such as smoking, drinking, irregular A number of studies from different workers
diet, and dietary habits. Polyphenol act as an have documented the anti-carcinogenic features
antioxidant, it removes the free radicals and of natural polyphenols. Natural polyphenols have
to stimulate certain metal chelation reactions. anticancer effects mainly due to their powerful
Singlet oxygen, peroxynitrite, and hydrogen antioxidant and anti-inflammatory actions,
peroxide, as different reactive oxygen species, are additionally their effectiveness to modulate
required to be constantly removed from cells to molecular targets and signaling pathways,
keep healthy metabolic function. Several benefits which were affiliated with cell life, migration,
may be associated with ion transport systems by separation, proliferation, immune responses,
eliminating and decreasing the concentrations of detoxification enzymes, angiogenesis, hormone
reactive oxygen species (free radicals). activities, etc. 30-35 .Including, anthocyanins,
The antioxidant nature of polyphenols delphinidin has strong anticancer activities; it
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follows the mechanism of induced apoptosis decrease the expression of cyclind1, which is
and cell cycle arrest in different classes of most possible due to the inhibiting property of
cancer. Peonidin-3-glucoside and cyanidin-3- these compounds in the propagation of K562 and
glucoside induce apoptosis and selectively reduced maintaining additional cells in the G0/G1 phase45.
cell proliferation and abnormal development with Cardiovascular Diseases and Polyphenols
HER2 positive breast cancer, and also repressed A c co rd i n g to t h e Wo r l d H e a l t h
lung cancer cells growth by down-regulating the Organization (WHO) -Reports, Cardiovascular
matrix metalloproteinase (MMP) expression36-39. diseases (CVDs) are the key reason of death
Cyanidin-3-O-sambubioside has a preventive effect internationally. Approximately 17.9 million
and also suppresses the development of breast public died from CVDs in 2016; mean 31% of all
cancer cells40. total deaths number. About 85% of the above
Researchers proclaimed that non- mentioned death’s figure is because of heart
acylated monoglycosylated anthocyanins were attack and stroke. About 75 percent of the
well effective in suppressing the uncontrolled world’s deaths from CVDs happen in low- and
growth of cancer cell, as compared to anthocyanins middle-income countries46. Heart Disease and
with pelargonidin aglycone and tri glycosylation41. Stroke Statistics - 2019 keep up to date from the
Many polyphenolic compounds, like quercetin, American Heart Association mentions that: 116.4
catechins, isoflavones, lignans, flavanones, ellagic million or 46% of US people age of above 18 are
acid, anthocyanidins, xanthohumol, resveratrol, likely to have hypertension (high blood pressure).
or curcumin showed protective and suppressive According to the published data of (WHO) 2016,
effects by different mechanisms in some cancerous about 2303 deaths were reported every day from
model’s studies42. Epigallocatechin gallate (EGCG), CVD47. Cardiovascular diseases (CVDs) are a kind
also recognized as epigallocatechin-3-gallate, of diseases in which heart or blood vessels are
is an ester of epigallocatechin and gallic acid, involved.
a kind of catechin, and components of green Polyphenols from different sources
tea, which reduces the risk of various cancers of food like cocoa, coffee, tea, and apples
like those of the bladder, prostate, esophagus, have been related with a number of health-
and stomach 43.Curcumin (diferuloylmethane) associated benefits, as well as cardiovascular
has antitumor potentials (which suppress the disease6-7, 48-52. Epidemiological studies recommend
cellular proliferation and angiogenesis), prevents that consumption of polyphenols because it is
of tumor cell cycle progression, anti-kinase clearly associated with the reduction in the CVD
activity and inducing programmed cell death prevalence53-54. Currently, researchers suggested
in vitro and in vivo. It also controls NF-KB that owing to antithrombotic, anti-inflammatory,
activation AP-1 DNA binding, signal transducer and anti-aggregative character of Polyphenolic
and also activatesthetranscription-3 (STAT 3) compounds; they are acting at the molecular
phosphorylation in vitro44. Flavonoids of astragalus level, improving endothelial function, and
mongholicus have much biological activity such reducing platelet aggregation as well. Thus, in
as anti-injury and anti-mutation properties, and the prevention and treatment of cardiovascular
also have an important suppression outcome on disease, polyphenolic compounds play important
the human being hepatocellular carcinoma BEL- roles. It is suggested that people with a better
7402 cells and induce the cell cycle retardation consumption of flavonoids in their diets have a
in the G0/G1 phase, particularly in the G1 47% lower occurrence of cardiovascular incidence
phase. Cyclind1 starts to express between the G0 against to those with the lowest consumption55.
and the G1 phases and takes part in the regulation It was suggested that the consumption of flavan-3-
of the G1 phase due to the association of cyclin- ol from different nutritional sources are beneficial
dependent kinases 4 (CDK4) and 6 (CDK6), for cardiometabolic consequences, also decreasing
conducting to the progression of the cells into the the menace of diabetes, and cardiovascular-
S phase (replication of DNA). An uncontrollable associated results (i.e. cholesterol levels, blood
expression of cyclind1 deregulation of the cell pressure, and myocardial infarction). Several
cycle will be resulting from CDK4/CDK6. Flavonoids foods like tea; nuts, cocoa (chocolate), grapes, and
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Mustafa et al., J. Pure Appl. Microbiol., 14(1), 47-61 | March 2020 | https://doi.org/10.22207/JPAM.14.1.08
legumes consuming regularly have a high content over 2-4 years, compared with those taking the
of flavan-3-ols, a commonly known polyphenol56-61. lowest amounts. Among polyphenolic compounds,
Rich source of anthocyanins, a kind of flavonoids, anthocyanins and procyanidins have the most
are red and blue fruits and vegetables, especially potent anti-diabetic effect, which is found in red,
blueberries, raspberries, strawberries, bilberries, purple, and blue foods, such as berries, currants,
red grapes, and cherries, etc. A dietary intake and grapes, bark, leaves, popular drinks like cocoa,
of anthocyanins, similar to other polyphenols, coffee, green tea and seeds of many plants and
are metabolized by the host and the micro plant-derived food74-75.
biome to shape active metabolite that has Alzheimer’s disease and Polyphenols
anti-inflammatory characteristics and produce Alzheimer’s disease (AD) is another
positive vascular outcome, and also decrease major widespread neurodegenerative disorders,
the threat of myocardial infarction in men and which is due to the damage of nerve structure
women and cause additional favorable effects and function and eventually leading to the death
on cardiovascular risk factors62-64. Resveratrol of nerve cells in the human brain, affecting older
is a Stilbene and is largely occurs in grapes, people worldwide76-77. According to the recently
red wine, and berries have anti-inflammatory revealed facts from the World Health Organization
and antioxidant actions, and also activates the (WHO)-Worldwide, about 50 million inhabitants
sirtuins, which produce a positive effect on are suffering from Alzheimer’s disease or other
aging. It is reported, that supplementation of dementias, and the number will be exceeded
resveratrol appreciably controls fasting glucose, 152 million by the year 2050 About 60 percent of
total cholesterol, C-reactive protein (CRP), and people living with dementia worldwide are from
systolic and diastolic blood pressure. Quercetin, a a low- or middle-income country78.
flavonol found in the apple that has been appeared Genetic and environmental aspects are
to enhance the endothelial function, reduces considered as a risk concern in Alzheimer’s disease
systolic blood pressure, and decreases the menace (AD)79-80. Free radicals are highly reactive chemical
of cardiovascular disease65-69. groups having an odd number of electrons and
Diabetes and Polyphenols are formed in course of the both physiological
Diabetes is one of the most major and pathological processes. While reactive
community health problems in the world and oxygen species (ROS) take part in a number of
according to WHO estimates that diabetes was the cellular and signaling pathways at physiological
7th leading cause of death in 201670-71. A healthy concentrations (cell cycle regulation, phagocytosis,
diet can facilitate to prevent the development and enzyme activation), an undue production of
of diabetes and can retard the complication of ROS have various unhealthy effects together with
diabetes. Polyphenols -rich diets have the potential DNA, lipid, and protein damage81-84. An inequality
to defend against type 2- diabetes (formerly in the status of oxidant-antioxidant could lead
called non-insulin-dependent, or adult-onset). to cell damage. Oxidative impair as a outcome
Polyphenolic compounds stimulate the secretion of ROS has been suggested in the pathogenesis
of insulin, a hormone that is needed to shuttle [the development, mechanism, and progress of
sugar from the bloodstream into the cells and disease] of neurodegenerative diseases, cancer,
keeping the blood sugar levels normal. It may also diabetes, and aging85.
prevent the breakdown of starch into simple sugars, C o m p re h e n s i ve a ca d e m i c wo r ks
and keeping the blood sugar level stable after reported that the superoxide anion; the hydroxyl
meals. Various studies suggested that polyphenol- radical, hydrogen peroxide, and nitric oxide
rich diets may help in, to lower the fasting blood play a vital character in the in oxidative stress
sugar levels, higher glucose, tolerance, and eventually leading to neurodegenerative disease
increasing insulin sensitivity — all these factors Alzheimer 86-87. ROS is, however, removed by
are protecting from type 2 diabetes72-73. It is the defense mechanisms, called as enzymatic
also suggested that people taking the highest and non-enzymatic antioxidants. Polyphenolic
amounts of polyphenol-rich diets had up to a 57% compounds have antioxidant character and
reduce menace of developing type 2 diabetes take part in a foremost neuroprotective role. It
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action by the alteration in the permeability of cell health effects. Therefore, the nutritionists have
membranes, the changes in different intracellular a task to educate communities on the health
functions induced by hydrogen bonding of the benefits of phytochemicals. People should also
phenolic compounds to enzymes or by the need to know foods rich in these phytochemicals
change of the cell wall rigidity along with integrity and preparation methods of enhancing the
losses because of different interactions with the bioavailability of different phytochemicals.
cell membrane. Therefore, the elevation of the Foodstuff rich in polyphenols for instance fruits,
lipophilic nature of phenolic compounds enhances vegetables, nuts, and seeds act as a natural
their antimicrobial activity by favoring their medicine to enhance our health quality and life
interaction with the cell membrane109-113. span. There is no doubt that our food habits can
determine our destiny and fate. A very common
DISCUSSION proverb is used “Prevention is better than cure”.
Recently, the 13th World Congress
on the Application of Polyphenols: Malta ACKNOWLEDGEMENTS
Polyphenols 2019, (International Society of The authors would like to acknowledge
Antioxidants in Nutrition and Health (ISANH) the keen support for this work of the Department
and the International Society of Microbiota) was of Chemistry, Faculty of Science, and University of
concluded on October 1, 2019 at Malta. They made Tabuk, Saudi Arabia.
a long discussion on various approaches in product
development, exploitation of novel sources of CONFLICT OF INTEREST
phenolic compounds, characterization, and the The authors declare that there is no
application of novel nutraceuticals based on plant conflict of interest.
phenolic compounds and also new processes for
extraction and formulation of polyphenols on a FUNDING
wide scale. They also emphasized on the novel None.
approaches for the scientific developments with
regards to polyphenols. Further, the industrialists AUTHORS’ CONTRIBUTION
and scientific communities mulled together to All authors listed have made a substantial,
explore the promising future of polyphenols, to direct and intellectual contribution to the work,
meet the common goal of serving humanity at and approved it for publication.
large.
Finally, based on the present study and DATA AVAILABILITY
analysis, one can say that, it needs a comprehensive All datasets generated or analyzed during
investigation into the interrelationship between this study are included in the manuscript.
the bioavailability, metabolism, and bioactivity,
including the prevention of neurodegenerative ETHICS STATEMENT
diseases, Non-Communicable diseases (NCDs), Not applicable.
such as most cancers, type 2 diabetes, and cardio
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