The biological properties of polyphenols comprise anticancer, antioxidant, and anti-inflammatory impacts.

Polyphenols have anti-microbial and anti-cariogenic properties and are an important source as anti-infective elements towards against antibiotic-resistant human pathogens. As antioxidants, polyphenols are the most abundant a Man daily diet.

In the last few years, a sufficient volume of researches evaluating the physiological behavior of dietary-derived bioactive and dietary ingredients with functional properties have noticeably raised.

Foodstuffs having bioactive compositions are reducing the risks of many chronic diseases that are getting the key sources of worldwide morbidity and mortality rates 17, Classification of Various Polyphenols Polyphenols can be categorized as according to the phenol rings exist and the structural parts that unite these rings collectively, characterizing the molecules as phenolic acids, flavonoids, stilbenes, and lignans, as shown in [Fig.

Polyphenols may be combined with different carbohydrates and organic acids together. Phenolic acids They are non-flavonoid polyphenolic compounds, subdivided into two key groups, derivatives of benzoic acid and cinnamic acid; depend on the arrangement of C1-C6 and C3-C6 as shown in Fig.

Flavonoids They have a simple structure with two benzenoid rings A and B that are bonded mutually by 3 carbon atoms that make an oxygenated heterocyclic ring C , further subdivided as flavonols, flavones, isoflavones, flavanones, anthocyanidins, and flavanols catechins and proanthocyanidins.

Flavonoids and phenolic acids are the most common classes. Flavonoids or bioflavonoids are classified as plant and fungi secondary metabolites.

Flavonoids have the common arrangements with a carbon atoms which contains two benzene rings A and B and a heterocyclic ring C , depicted in Fig. Classified as a diarylethene, it has a central ethylene group attached with one phenyl group substituents on each end of the carbon-carbon double bond Fig.

Lignans The lignans are a large collection of polyphenols present in plant life. Flaxseed and sesame are the best sources of lignans than most other foods.

Leading Food sources with Polyphenols More than 8, types of polyphenols have been identified. Polyphenols are found in high amount mainly, in coffee, berries, and dark chocolate, cocoa powder, olive oil, in certain spices and seasonings, like cloves and star anise.

Some of the top sources of polyphenol foods that should be added in daily diet intake have been shown in Table 1. Table 1 : Daily diet intake of polyphenols in various food items.

Olive Oil The least processed form of olive oil is called Extra-virgin olive oil; it has the dense collection of polyphenolic compounds, extracted from the olive fruit. Consuming of olive oil as a diet inappropriate quantity helps to protect from heart disease, strokes, metabolic syndrome, and some kinds of cancer diseases.

Health Effect of Polyphenols There is no doubt that food can act as natural medicine, our diet can determine our destiny and fate. Polyphenols including flavonoids, tannins, lignans, and stilbenes are the most abundant phytochemicals in our diet. Polyphenol-rich foods found in fruits, vegetables, nuts, and seeds are medicine to enhance our health quality and life span.

The modes of action of different polyphenolic compounds, more than ever as correlated to reduced menace of disease in individuals, are not entirely explained. A number of show antioxidant behaviors, while others activate defense mechanisms that improve the response to oxidative stress and preventing from extensive damage.

They have been associated with numerous valuable effects on human being health. Currently, many researchers have taken an interest in polyphenols, because of their antioxidant nature, large quantity in our food, and their action in the prevention of different diseases related to oxidative stress, such as cancer, cardiovascular and neurodegenerative diseases.

Intake of polyphenols can be achieved by consuming a large variety of plant foodstuff because the main resource of polyphenols is dietary. This dietary polyphenol includes honey, most legumes and fruits are all rich in polyphenols.

Meanwhile, fruits such as apples, pomegranate, strawberries, blackberries, Aronia berries, cranberries, blueberries, raspberries, cherries, cantaloupe, grapes, plums, and pears are all rich in polyphenols.

In addition, vegetables such as parsley, broccoli, celery, cabbage, and onion, green tea, white tea, black tea, chocolate, as well as olive oil, are rich in polyphenols Polyphenols as an Antioxidant Compounds that repress oxidation are called antioxidants.

Oxidation is a chemical process that is able to generate free radicals. Atom or group of atoms that has an unpaired electron called free radicals. They are generally unstable and very reactive for the reason that unpaired electrons are likely to form pairs with other electrons.

When the metabolism taking place in a living organism: an oxygen molecule O 2 undergoes four-electron reduction. Reactive oxygen metabolites are generated in this process, maybe due to the excitation of electrons, the addition of energy or interaction with transition elements.

These generated reactive oxygen metabolites are extremely reactive than the oxygen molecule, are called active oxygen species. In living cells, the formations of free radicals are taking place mainly due to the homolytic chemical bond fission, photolysis, and radiolysis, and due to red-ox reactions.

The free radicals are initiating the chain reaction in the living organism, which may lead to cell damage, thus inducing various diseases. Antioxidants are such substances that terminate the chain reaction, initiated by the free radicals in the living organism. In other words, antioxidants neutralize or deactivate the action of reactive oxygen species free radicals , and protect the living organism from the harmful consequence of the free radicals.

The difference between the formation of highly reactive oxygen groups free radicals and antioxidant defenses, called Oxidative stress. Produced free radical species attack the existing pro-oxidants molecules or ions because it has a very high affinity to combine with others.

The human body depends on various endogenous resistance mechanisms to defend against free radical-induced cell injure. Impair of the body cells due to reactive oxygen species free radicals plays a significant character in the aging development, and in disease growth or development.

It has been recommended that an insufficient nutritional consumption of a nutrient may be compromised with the efficiency of these antioxidant resistance mechanisms.

Many daily practices are directly related to oxidative stress, such as smoking, drinking, irregular diet, and dietary habits. Polyphenol act as an antioxidant, it removes the free radicals and to stimulate certain metal chelation reactions. Singlet oxygen, peroxynitrite, and hydrogen peroxide, as different reactive oxygen species, are required to be constantly removed from cells to keep healthy metabolic function.

Several benefits may be associated with ion transport systems by eliminating and decreasing the concentrations of reactive oxygen species free radicals. The antioxidant nature of polyphenols PhOH is based on the contribution of an H-atom, which disrupts and terminates the succession reactions initiated by the free radicals in the living organism.

More than 8, types of natural polyphenols have been identified. Meanwhile, polyphenols are made up of multiple phenol units and are found naturally in many dietary sources, associated with many health benefits due to their antioxidant content Anticancer effects and Polyphenols Cancer treatment and cancer prevention is a big challenge for the whole scientific community.

According to WHO January reports cancer is the next most important reason of death internationally and is likely to account for 9. In other words, approximately one in six deaths due to cancer reported internationally.

A balanced diet, to get the proper nutrition is a better strategy in prevention more than in cancer therapy. Dietary adaptation and alteration are an important approach to cancer control.

Consumption of fruits and vegetables may have an impressive defensive outcome against several cancers such as the oesophagus, colorectal, breast, endometrium, and kidney. Healthy eating is a way of life that helps to check the development of diet-related cancers will also decreases the probability of other non-communicable diseases [NCDs] A number of studies from different workers have documented the anti-carcinogenic features of natural polyphenols.

Natural polyphenols have anticancer effects mainly due to their powerful antioxidant and anti-inflammatory actions, additionally their effectiveness to modulate molecular targets and signaling pathways, which were affiliated with cell life, migration, separation, proliferation, immune responses, detoxification enzymes, angiogenesis, hormone activities, etc.

Including, anthocyanins, delphinidin has strong anticancer activities; it follows the mechanism of induced apoptosis and cell cycle arrest in different classes of cancer. Peonidinglucoside and cyanidinglucoside induce apoptosis and selectively reduced cell proliferation and abnormal development with HER2 positive breast cancer, and also repressed lung cancer cells growth by down-regulating the matrix metalloproteinase MMP expression Cyanidin O -sambubioside has a preventive effect and also suppresses the development of breast cancer cells Researchers proclaimed that non-acylated monoglycosylated anthocyanins were well effective in suppressing the uncontrolled growth of cancer cell, as compared to anthocyanins with pelargonidin aglycone and tri glycosylation Epigallocatechin gallate EGCG , also recognized as epigallocatechingallate, is an ester of epigallocatechin and gallic acid, a kind of catechin, and components of green tea, which reduces the risk of various cancers like those of the bladder, prostate, esophagus, and stomach Curcumin diferuloylmethane has antitumor potentials which suppress the cellular proliferation and angiogenesis , prevents of tumor cell cycle progression, anti-kinase activity and inducing programmed cell death in vitro and in vivo.

It also controls NF-KB activation AP-1 DNA binding, signal transducer and also activatesthetranscription-3 STAT 3 phosphorylation in vitro Cyclind1 starts to express between the G0 and the G1 phases and takes part in the regulation of the G1 phase due to the association of cyclin-dependent kinases 4 CDK4 and 6 CDK6 , conducting to the progression of the cells into the S phase replication of DNA.

Cardiovascular Diseases and Polyphenols According to the World Health Organization WHO -Reports, Cardiovascular diseases CVDs are the key reason of death internationally. Approximately Heart Disease and Stroke Statistics — keep up to date from the American Heart Association mentions that: According to the published data of WHO , about deaths were reported every day from CVD Cardiovascular diseases CVDs are a kind of diseases in which heart or blood vessels are involved.

Polyphenols from different sources of food like cocoa, coffee, tea, and apples have been related with a number of health-associated benefits, as well as cardiovascular disease , Epidemiological studies recommend that consumption of polyphenols because it is clearly associated with the reduction in the CVD prevalence Currently, researchers suggested that owing to antithrombotic, anti-inflammatory, and anti-aggregative character of Polyphenolic compounds; they are acting at the molecular level, improving endothelial function, and reducing platelet aggregation as well.

Thus, in the prevention and treatment of cardiovascular disease, polyphenolic compounds play important roles. It was suggested that the consumption of flavanol from different nutritional sources are beneficial for cardiometabolic consequences, also decreasing the menace of diabetes, and cardiovascular- associated results i.

cholesterol levels, blood pressure, and myocardial infarction. Several foods like tea; nuts, cocoa chocolate , grapes, and legumes consuming regularly have a high content of flavanols, a commonly known polyphenol Rich source of anthocyanins, a kind of flavonoids, are red and blue fruits and vegetables, especially blueberries, raspberries, strawberries, bilberries, red grapes, and cherries, etc.

A dietary intake of anthocyanins, similar to other polyphenols, are metabolized by the host and the micro biome to shape active metabolite that has anti-inflammatory characteristics and produce positive vascular outcome, and also decrease the threat of myocardial infarction in men and women and cause additional favorable effects on cardiovascular risk factors Resveratrol is a Stilbene and is largely occurs in grapes, red wine, and berries have anti-inflammatory and antioxidant actions, and also activates the sirtuins, which produce a positive effect on aging.

It is reported, that supplementation of resveratrol appreciably controls fasting glucose, total cholesterol, C-reactive protein CRP , and systolic and diastolic blood pressure. Quercetin, a flavonol found in the apple that has been appeared to enhance the endothelial function, reduces systolic blood pressure, and decreases the menace of cardiovascular disease Diabetes and Polyphenols Diabetes is one of the most major community health problems in the world and according to WHO estimates that diabetes was the 7th leading cause of death in A healthy diet can facilitate to prevent the development of diabetes and can retard the complication of diabetes.

Polyphenols -rich diets have the potential to defend against type 2- diabetes formerly called non-insulin-dependent, or adult-onset.

Polyphenolic compounds stimulate the secretion of insulin, a hormone that is needed to shuttle sugar from the bloodstream into the cells and keeping the blood sugar levels normal.

It may also prevent the breakdown of starch into simple sugars, and keeping the blood sugar level stable after meals. Various studies suggested that polyphenol-rich diets may help in, to lower the fasting blood sugar levels, higher glucose, tolerance, and increasing insulin sensitivity — all these factors are protecting from type 2 diabetes Among polyphenolic compounds, anthocyanins and procyanidins have the most potent anti-diabetic effect, which is found in red, purple, and blue foods, such as berries, currants, and grapes, bark, leaves, popular drinks like cocoa, coffee, green tea and seeds of many plants and plant-derived food Free radicals are highly reactive chemical groups having an odd number of electrons and are formed in course of the both physiological and pathological processes.

While reactive oxygen species ROS take part in a number of cellular and signaling pathways at physiological concentrations cell cycle regulation, phagocytosis, and enzyme activation , an undue production of ROS have various unhealthy effects together with DNA, lipid, and protein damage An inequality in the status of oxidant-antioxidant could lead to cell damage.

Oxidative impair as a outcome of ROS has been suggested in the pathogenesis [the development, mechanism, and progress of disease] of neurodegenerative diseases, cancer, diabetes, and aging Comprehensive academic works reported that the superoxide anion; the hydroxyl radical, hydrogen peroxide, and nitric oxide play a vital character in the in oxidative stress eventually leading to neurodegenerative disease Alzheimer ROS is, however, removed by the defense mechanisms, called as enzymatic and non-enzymatic antioxidants.

Polyphenolic compounds have antioxidant character and take part in a foremost neuroprotective role. Workers also reported that walnut Walnut polyphenols have the best efficacy among the nuts extract has a strong potential to prevent amyloid-beta peptide-induced oxidative stress in PC12 cells Oral flora, teeth, and dietary factors play a role in dental caries disease.

Dietary carbohydrates sucrose or sugars are occupied into dental plaque and broken down into organic acids lactic acid by bacteria exist in dental plaque on the outer surface of tooth. The antibacterial role of polyphenols, found in tea, coffee, red grape seeds, and cocoa can also play a role in the keeping off from cariogenic processes: they may decrease the rate of growth of bacteria and keeping the tooth surface protected, and also can have inhibitory effects on the enzymatic activity of glucosyltransferase and amylase.

Flavonoids seem to be a favorable anti-cariogenic molecule Anti cariogenic effects of phenolic compounds can be separated into two groups: I Plant extracts having high concentrations of polyphenols, without the recognition of particular compounds present in the extracts and II Antibacterial activity of specific polyphenolic compounds.

The extracts from unfermented cocoa, green tea, and red grape seeds, all with a high polyphenols content is effective against S. mutants and periodontal diseases QuercetinO-α-L-arabinose-pyranoside guaijaverin , an active flavonoid compound has high probable anti plaque outcome by inhibiting the development of S.

mutants Magnolol and honokiol isolated from extracts of Magnolia sp. A lavandulyl flavone extracted from Sophora Exigua Craig absolutely inhibited the oral bacterial growth, as well as primary cariogenic mutans streptococci, other oral streptococci, actinomycetes, and lactobacilli Isoprenyl flavones isolated from Artocarpus heterophyllus and erycristagallin isolated from Erythrina variegate exhibited antibacterial action against cariogenic bacteria In the last few years, polyphenols extracted from Perillafrutescens var.

japonica seeds have suppressive action against oral cariogenic Streptococci and periodontopathic Porphyromonas gingivalis. Polyphenols isolated from Perilla seed and flavonoid luteolin have active inhibiting property against bacterial growth The regular intake of black tea theaflavins antioxidant polyphenols considerably decreased caries development by Antimicrobial activity of Polyphenolic Compounds Polyphenolic compounds show significant antibacterial activity as well.

Phenolic compounds found in the fruits may well be used as a potential natural antibacterial agent. The tropical fruits like guava, persimmon, and sweetsop, have an antioxidant and antibacterial activity that supported the possibility of developing the fruits into a novel natural resource and functional food in addition to the new natural antimicrobial agents and food preservatives.

Antibacterial action mechanisms of the phenolic compounds are not so far completely explained but these compounds are recognized to involve several sites of action at the cellular level Many workers explained antibacterial action by the alteration in the permeability of cell membranes, the changes in different intracellular functions induced by hydrogen bonding of the phenolic compounds to enzymes or by the change of the cell wall rigidity along with integrity losses because of different interactions with the cell membrane.

Therefore, the elevation of the lipophilic nature of phenolic compounds enhances their antimicrobial activity by favoring their interaction with the cell membrane Recently, the 13th World Congress on the Application of Polyphenols: Malta Polyphenols , International Society of Antioxidants in Nutrition and Health ISANH and the International Society of Microbiota was concluded on October 1, at Malta.

They made a long discussion on various approaches in product development, exploitation of novel sources of phenolic compounds, characterization, and the application of novel nutraceuticals based on plant phenolic compounds and also new processes for extraction and formulation of polyphenols on a wide scale.

They also emphasized on the novel approaches for the scientific developments with regards to polyphenols. Further, the industrialists and scientific communities mulled together to explore the promising future of polyphenols, to meet the common goal of serving humanity at large.

Finally, based on the present study and analysis, one can say that, it needs a comprehensive investigation into the interrelationship between the bioavailability, metabolism, and bioactivity, including the prevention of neurodegenerative diseases, Non-Communicable diseases NCDs , such as most cancers, type 2 diabetes, and cardio metabolic effects.

A poor dietary practice has contributed a big percentage in the growth of chronic diseases, as well as diabetes, hypertension, cancer, and cardiovascular diseases. The phophenolic compounds have been related with numerous advantageous consequences on individual health.

Detailed awareness of the bioavailability of the nutritional polyphenols will facilitate us to classify those that are beneficial and protective for public health effects. Therefore, the nutritionists have a task to educate communities on the health benefits of phytochemicals. People should also need to know foods rich in these phytochemicals and preparation methods of enhancing the bioavailability of different phytochemicals.

Foodstuff rich in polyphenols for instance fruits, vegetables, nuts, and seeds act as a natural medicine to enhance our health quality and life span. There is no doubt that our food habits can determine our destiny and fate. CONFLICT OF INTEREST The authors declare that there is no conflict of interest.

Open Access. This article is distributed under the terms of the Creative Commons Attribution 4. Journal About JPAM Articles Current Issue Spl. Issue, Dec. Journal of Pure and Applied Microbiology. Abstract Keywords Introduction Discussion Conclusion Declarations References.

Polyphenols more than an Antioxidant: Role and Scope. Syed Khalid Mustafa 1 , Atif Abdul Wahab A. Oyouni 2 , Meshari M. There is no substantial evidence that reactive oxygen species play a role in the process of skin aging. Controlled long-term studies on the efficacy of low molecular weight antioxidants in the prevention or treatment of skin aging in humans are absent.

Antioxidant levels of purified anthocyanin extracts were much higher than expected from anthocyanin content indicating synergistic effect of anthocyanin mixtures. Contents move to sidebar hide. Article Talk. Read Edit View history. Tools Tools. What links here Related changes Upload file Special pages Permanent link Page information Cite this page Get shortened URL Download QR code Wikidata item.

Download as PDF Printable version. Blackberries are a source of polyphenols. Reactive oxygen species promote oxidized LDL. Corvallis, OR: Micronutrient Information Center, Linus Pauling Institute, Oregon State University. November Retrieved 31 January doi : PMID Natural Products Information Center.

Archived from the original on March 6, Because of the immense variety and many different classes of polyphenol compounds, determining structure—activity relationships SARs for antioxidant properties of polyphenols is a challenging undertaking.

For identification of effective polyphenol antioxidants, determining SARs for these compounds is required to realize their potential to treat and prevent diseases caused by oxidative damage. Cheng and Breen have used cyclic voltammetry to show that four polyphenol compounds, baicilein, naringenin, luteolin, and quercetin Fig.

The two compounds with catechol moieties on the B ring luteolin and quercetin are more potent inhibitors of the Fenton reaction than the two compounds without catechols baicilein and naringenin [ ]. Based on the large stability constants for iron—catecholate complexes, it would seem, therefore, that iron binding at the catecholate group may be responsible for the greater antioxidant activity observed for luteolin and quercetin.

However, baicilein has a gallol group on the A ring rather than the B ring, which could also bind iron. Since baicilein was a weaker antioxidant in this system, Cheng and Breen concluded that substituents on the B ring more significantly affect antioxidant activity.

The higher antioxidant activity of phenol substituents on the B ring as compared to the A ring was confirmed by Jovanovich et al.

In addition to reporting that compounds with no phenol groups had negligible antioxidant activity in a lipid peroxidation model evaluating antioxidant activities of polyphenols, Arora et al.

stated that phenol substituents on the A ring contribute little to the antioxidant activity of polyphenols. However, in this study they also tested one compound 7,8-dihydroxyflavone with a catechol substituent on the A ring that had similar antioxidant activity to compounds with B ring catechol substituents.

Thus, the lower antioxidant activity of A ring polyphenols compared to B ring polyphenols may not apply universally. Khokar and Apenten [ ] compared polyphenol compounds with catechol and gallol moieties on the B ring as well as tannic acid , and concluded that these structural motifs are optimal for iron binding and antioxidant activity in vitro.

By quantifying a representative selection of polyphenol compounds for prevention of iron-mediated DNA damage, Perron et al. Furthermore, the IC 50 values for twelve polyphenols reported by Perron and coworkers correlated to the p K a value of the most acidic phenolic hydrogen of the polyphenol compounds Table 2 , representing the first predictive model of antioxidant potency as a function of iron-binding ability Fig.

This correlation, along with additional experiments, directly established iron binding as the mechanism of the observed antioxidant activity [ , ]. This predictive model allows the library of polyphenols to be efficiently screened for those with the highest iron-binding antioxidant activity.

The data points for myricetin and quercetin were omitted from the data set because of their non-gallol and non-catechol binding sites, respectively. Error bars for IC 50 values are within the size of the data points.

p K a values used in this figure are the averages of the literature values listed in Table 2. The SARs of polyphenols related to iron binding have generally been established for catechol and gallol containing compounds. In addition to these iron-binding groups, hydroxy-keto moieties may also contribute to antioxidant activity by binding iron.

for those with optimal antioxidant activity in vitro. After selecting the best candidates, the in vitro experiments should be followed by cell and animal studies, and eventually clinical trials for the most promising polyphenol antioxidants.

Iron-mediated oxidative damage is not limited to living organisms. Contreras et al. Tiron Fig. In contrast, Binbuga et al. This preservative effect of n -propyl gallate was attributed primarily to its antifungal properties, since it may interfere with the Fenton reaction and redox cycles that wood-decaying brown rot fungi use to decompose wood [ , , ].

In addition to wood preservation, polyphenol compounds have been widely studied for use as preservatives for food, cosmetics, and pharmaceuticals, with many patents for these applications both nationally and internationally related to their antioxidant properties [ — ].

The FDA has also approved n -propyl gallate for use as a food preservative [ ]. However, most patents discussing polyphenol preservative mechanisms do not cite metal chelation as a cause of their antioxidant activity, instead claiming the radical scavenging ability often attributed to these compounds.

The formation of iron—polyphenol complexes has been attributed to negative aspects in foods as well, such as off-color development or browning of bruised or sliced fruits [ ]. Similar polyphenol oxidation pathways occur in polyphenol oxidase and tyrosinase, two enzymes that utilize both a metal ion and O 2 to oxidize phenolic compounds [ , ].

While these enzymes typically have copper-containing active sites, an iron-containing tyrosinase has been isolated from tea leaves [ ]. Based on the limited research in this area, the use of polyphenol compounds as preservatives for food and wood seems promising, although selection of specific polyphenol compounds with antioxidant properties will be important, since some appear to actually accelerate rotting processes under certain conditions.

Therefore, as with polyphenol antioxidants for use in vivo, further testing is needed to determine both the conditions under which polyphenols have preservative effects, and the SARs of polyphenol compounds as related to antioxidant, preservative, and antibiotic properties.

Although the focus of this review is on the antioxidant activity of polyphenol compounds, several reports have described prooxidant behavior for polyphenols, and this activity must not be overlooked. A review of the prooxidant and toxic effects of polyphenols both in vitro and in vivo was published by Schweigert et al.

In these cases, the polyphenol compound can reduce the metal ion via an outer-sphere electron transfer, making it available for reaction with H 2 O 2 or other sources of radicals. Once again, this implies that iron binding is required for polyphenol antioxidant activity, or at the very least, prevention of prooxidant activity.

It must be noted that the intracellular cytoplasmic environment is known to be quite reducing, due to the many reductants present inside the cell, such as NADH, glutathione, thioredoxin, ascorbic acid, and citric acid [ , , ].

Thus, any non-protein-bound metal ions would most likely be present in their reduced forms in vivo [ ]. Due to the deleterious effects of prooxidant activity, however, it is essential to understand both the antioxidant and prooxidant behavior of polyphenol compounds.

It is interesting that polyphenol compounds can display both antioxidant and prooxidant activity under very similar conditions. Often these conditions are quite similar to those in biological systems, however, there are not usually ligands as strongly chelating as EDTA other than proteins in cells, and these are highly specialized and prevent iron-mediated prooxidant activity.

Therefore, the conditions for polyphenol prooxidant activity are actually quite limited, often not biologically relevant, and therefore may be of less concern to humans who ingest these compounds in food sources.

However, this body of work showing prooxidant activity for polyphenols when they cannot directly chelate iron does stress the essentiality of iron-binding as a viable antioxidant mechanism for these compounds. Since these reactions form H 2 O 2 , polyphenol compounds may contribute to cellular oxidative stress.

An example of this proposed SOD-like activity was reported by de Souza et al. However, the products of this reaction were not isolated or characterized; therefore, such reaction products must be further characterized to confirm the SOD-like mechanism for iron-polyphenol complexes.

This polyphenol-bound iron would not be available to react with H 2 O 2 , and thus the H 2 O 2 would be decomposed by catalase or peroxidase enzymes, such as glutathione peroxidase [ — ]. The interactions between iron, polyphenols, and ROS and RNS are extremely complex, so it is necessary to explore these systems carefully, using diverse and complementary experimental techniques studying the structure of iron—polyphenol complexes, for example, combined with their ROS reactivity as examined using EPR spectroscopy , to positively identify the mechanisms and products of these reactions.

Although the purpose of this review is to highlight the iron binding properties of polyphenol compounds, due to similarities in copper-mediated ROS generation, the interactions between polyphenols and copper should not be ignored.

This tendency toward copper reduction, coupled with the tendency of polyphenol compounds to oxidize results in complex copper—polyphenol interactions, especially in the presence of ROS [ — ].

To the best of our knowledge, only Andrade et al. and Perron, et al. Andrade et al. examined the antioxidant activity of tannic acid Fig. From their results, they calculated an IC 50 value of 5. Using gel electrophoresis, Perron et al.

They showed inhibition of copper-mediated DNA damage for EGCG Fig. In contrast, EC and EGC displayed prooxidant activity under the same conditions, whereas ECG displayed both prooxidant activity and antioxidant activity at low 0.

Based on these experiments, a copper redox-cycling mechanism was proposed for the prooxidant activity observed for some polyphenols under these conditions [ , , , ].

Recently, however, non-protein-bound copper pools have been found in the mitochondria and neuronal cells of higher organisms [ , ], and mis-regulation of copper homeostasis results in higher cellular concentrations and increased oxidative stress [ , — ].

Therefore, elucidating the antioxidant and prooxidant mechanisms of polyphenol—copper interactions will be important for a complete understanding of polyphenol activity in vivo.

These findings stress the need for caution in experimental design: in addition to the polyphenol compounds, the metal ion must be specifically chosen to examine the metal—antioxidant interactions.

Since results are highly dependent on experimental conditions, it should be the goal of researchers to design the most biologically relevant experiments possible.

Because iron-mediated damage to biomolecules such as lipids and DNA is implicated in disease development, the iron-chelating mechanism of polyphenol antioxidant activity must be fully explored in addition to radical scavenging to understand polyphenol antioxidant behavior.

Polyphenols with gallol or catechol groups are generally the most potent antioxidants, primarily because of the large iron-binding stability constants for these groups. Also, compounds with the hydroxy-keto moiety can chelate iron, giving rise to antioxidant activity. As compared to radical scavenging, however, the iron-binding mechanism for polyphenol antioxidant activity is relatively underdeveloped.

Therefore, additional research is needed in several areas, including stability constant measurements for iron binding, p K a measurements of polyphenols, and additional cell studies and DNA damage prevention experiments to correlate in vitro and in vivo antioxidant activity of these compounds.

The goal of this work should be to develop biologically relevant predictive models and SARs for polyphenol compounds, as well as high-throughput screening methods for determining antioxidant or prooxidant behavior. These further studies will enable identification of highly effective polyphenol antioxidants for clinical trials to prevent or treat diseases caused by oxidative stress.

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