Representative chemical structure of one of many plant-derived polyphenols that comprisetannic acid. Such compounds are formed by esterification ofphenylpropanoid-derivedgallic acid to a monosaccharide (glucose) core.
The name derives from theAncient Greek wordπολύς (polus, meaning "many, much") and the word ‘phenol’ which refers to a chemical structure formed by attachment of an aromaticbenzenoid (phenyl) ring to ahydroxyl (-OH) group (hence the-ol suffix). The term "polyphenol" has been in use at least since 1894.[4]
The term polyphenol is not well-defined, but it is generally agreed that they are natural products with "severalhydroxyl groups onaromatic rings" including four principal classes: "phenolic acids, flavonoids, stilbenes, and lignans".[5]
Flavonoids include flavones, flavonols, flavanols, flavanones, isoflavones, proanthocyanidins, and anthocyanins. Particularly abundant flavanoids in foods arecatechin (tea, fruits),hesperetin (citrus fruits),cyanidin (red fruits and berries),daidzein (soybean),proanthocyanidins (apple, grape, cocoa), andquercetin (onion, tea, apples).[2]
The White–Bate-Smith–Swain–Haslam (WBSSH) definition[6] characterized structural characteristics common to plant phenolics used intanning (i.e., the tannins).[7]
In terms of properties, the WBSSH describes the polyphenols as follows:
Raspberry ellagitannin, atannin composed of 14 gallic acid units around a core of three units of glucose, with two gallic acids as simple esters, and the remaining 12 appearing in 6 ellagic acid-type units. Ester, ether, and biaryl linkages are present, see below.
According to Stéphane Quideau, the term "polyphenol" refers to compounds derived from theshikimate/phenylpropanoid and/or thepolyketide pathway, featuring more than one phenolic unit and deprived of nitrogen-based functions.[citation needed]
Ellagic acid, a molecule at the core of naturally occurring phenolic compounds of varying sizes, is itself not a polyphenol by the WBSSH definition, but is by the Quideau definition. Theraspberry ellagitannin,[8] on the other hand, with its 14gallic acid moieties (most in ellagic acid-type components), and more than 40 phenolic hydroxyl groups, meets the criteria of both definitions of a polyphenol. Other examples of compounds that fall under both the WBSSH and Quideau definitions include theblack teatheaflavin-3-gallate shown below, and the hydrolyzable tannin,tannic acid.[citation needed]
Theaflavin-3-gallate, a plant-derived polyphenol, an ester of gallic acid and atheaflavin core. There are nine phenolic hydroxyl groups and two phenolicether linkages.
Polyphenols, such as lignin, are larger molecules (macromolecules). Their upper molecular weight limit is about 800daltons, which allows for the possibility to rapidly diffuse across cell membranes so that they can reach intracellular sites of action or remain as pigments once the cellsenesces. Hence, many larger polyphenols are biosynthesizedin situ from smaller polyphenols to non-hydrolyzable tannins and remain undiscovered in the plant matrix. Most polyphenols contain repeating phenolic moieties of pyrocatechol, resorcinol, pyrogallol, and phloroglucinol connected byesters (hydrolyzable tannins) or more stable C-C bonds (nonhydrolyzablecondensed tannins).Proanthocyanidins are mostly polymeric units ofcatechin andepicatechin.
The C-glucoside substructure of polyphenols is exemplified by the phenol-saccharide conjugate puerarin, a midmolecular-weight plant natural product. The attachment of the phenol to the saccharide is by a carbon-carbon bond. Theisoflavone and its 10-atombenzopyran "fused ring" system, also a structural feature here, is common in polyphenols.
An example of a synthetically achieved small ellagitannin,tellimagrandin II, derived biosynthetically and sometimes synthetically by oxidative joining of two of the galloyl moieties of1,2,3,4,6-pentagalloyl-glucose
Extraction of polyphenols[12] can be performed using a solvent like water,hot water, methanol, methanol/formic acid, methanol/water/acetic or formic acid.Liquid–liquid extraction can be also performed orcountercurrent chromatography.Solid phase extraction can also be made on C18 sorbent cartridges. Other techniques are ultrasonic extraction, heat reflux extraction, microwave-assisted extraction,[13]critical carbon dioxide,[14][15] high-pressureliquid extraction[16] or use of ethanol in an immersion extractor.[17] The extraction conditions (temperature, extraction time, ratio of solvent to raw material, particle size of the sample, solvent type, and solvent concentrations) for different raw materials and extraction methods have to be optimized.[18][19]
Mainly found in the fruit skins and seeds, high levels of polyphenols may reflect only themeasured extractable polyphenol (EPP) content of a fruit which may also contain non-extractable polyphenols. Black tea contains high amounts of polyphenol and makes up for 20% of its weight.[20]
TheDMACA reagent is an histological dye specific to polyphenols used in microscopy analyses. Theautofluorescence of polyphenols can also be used, especially for localisation of lignin andsuberin. Where fluorescence of the molecules themselves is insufficient for visualization by light microscopy, DPBA (diphenylboric acid 2-aminoethyl ester, also referred to as Naturstoff reagent A) has traditionally been used, at least inplant science, to enhance the fluorescence signal.[22]
Polyphenolic content in vitro can be quantified byvolumetric titration. An oxidizing agent,permanganate, is used to oxidize known concentrations of a standard tannin solution, producing astandard curve. The tannin content of the unknown is then expressed as equivalents of the appropriate hydrolyzable or condensed tannin.[23]
Some methods for quantification of total polyphenol content in vitro are based oncolorimetric measurements. Some tests are relatively specific to polyphenols (for instance the Porter's assay). Total phenols (or antioxidant effect) can be measured using theFolin–Ciocalteu reaction.[14] Results are typically expressed as gallic acid equivalents. Polyphenols are seldom evaluated byantibody technologies.[24]
Other tests measure the antioxidant capacity of a fraction. Some make use of theABTS radicalcation which is reactive towards most antioxidants including phenolics,thiols andvitamin C.[25] During this reaction, the blue ABTS radical cation is converted back to its colorless neutral form. The reaction may be monitored spectrophotometrically. This assay is often referred to as theTrolox equivalent antioxidant capacity (TEAC) assay. The reactivity of the various antioxidants tested are compared to that ofTrolox, which is avitamin E analog.
New methods including the use ofbiosensors can help monitor the content of polyphenols in food.[29]
Quantitation results produced by the mean ofdiode array detector–coupled HPLC are generally given as relative rather thanabsolute values as there is a lack of commercially availablestandards for all polyphenolic molecules.[citation needed]
Some polyphenols are traditionally used asdyes inleather tanning. For instance, in theIndian subcontinent,pomegranatepeel, high in tannins and other polyphenols, or its juice, is employed in the dyeing of non-synthetic fabrics.[30]
Of some interest in the era of silver-based photography, pyrogallol and pyrocatechin are among the oldestphotographic developers.[31][32]
Natural polyphenols have long been proposed asrenewable precursors to produce plastics or resins bypolymerization withformaldehyde,[33] as well asadhesives for particleboards.[34] The aims are generally to make use of plant residues from grape, olive (calledpomaces), orpecan shells left after processing.[14]
The most abundant polyphenols are thecondensed tannins, found in virtually all families of plants. Larger polyphenols are often concentrated in leaf tissue, the epidermis, bark layers, flowers and fruits but also play important roles in the decomposition of forest litter, andnutrient cycles in forest ecology. Absolute concentrations of total phenols in plant tissues differ widely depending on the literature source, type of polyphenols and assay; they are in the range of 1–25% totalnatural phenols and polyphenols, calculated with reference to the dry green leaf mass.[35]
Polyphenols incorporate smaller parts and building blocks from simplernatural phenols, which originate from thephenylpropanoid pathway for the phenolic acids or theshikimic acid pathway forgallotannins and analogs. Flavonoids and caffeic acid derivatives are biosynthesized fromphenylalanine andmalonyl-CoA. Complex gallotannins develop through thein vitro oxidation of1,2,3,4,6-pentagalloylglucose or dimerization processes resulting in hydrolyzable tannins. For anthocyanidins, precursors of the condensed tannin biosynthesis,dihydroflavonol reductase andleucoanthocyanidin reductase (LAR) are crucial enzymes with subsequent addition of catechin and epicatechin moieties for larger, non-hydrolyzable tannins.[46]
Polyphenol oxidase (PPO) is an enzyme that catalyses the oxidation ofo-diphenols to produceo-quinones. It is the rapid polymerisation of o-quinones to produce black, brown or red polyphenolic pigments that causesfruit browning. In insects, PPO is involved in cuticle hardening.[48]
Polyphenols comprise up to 0.2–0.3% fresh weight for many fruits. Consuming common servings of wine, chocolate,legumes or tea may also contribute to about one gram of intake per day.[2][49] According to a 2005 review on polyphenols:
The most important food sources are commodities widely consumed in large quantities such as fruit and vegetables, green tea, black tea, red wine, coffee, chocolate, olives, and extra virgin olive oil. Herbs and spices, nuts and algae are also potentially significant for supplying certain polyphenols. Some polyphenols are specific to particular food (flavanones in citrus fruit, isoflavones in soya, phloridzin in apples); whereas others, such as quercetin, are found in all plant products such as fruit, vegetables, cereals, leguminous plants, tea, and wine.[50]
In a comparison of cooking methods, phenolic andcarotenoid levels in vegetables were retained better bysteaming compared tofrying.[52] Polyphenols in wine, beer and various nonalcoholic juice beverages can be removed usingfinings, substances that are usually added at or near the completion of the processing of brewing.[citation needed]
With respect to food and beverages, the cause ofastringency is not fully understood, but it is measured chemically as the ability of a substance to precipitate proteins.[53]
Astringency increases and bitterness decrease with the mean degree ofpolymerization. For water-soluble polyphenols, molecular weights between 500 and 3000 were reported to be required for protein precipitation. However, smaller molecules might still have astringent qualities likely due to the formation of unprecipitated complexes with proteins or cross-linking of proteins with simple phenols that have 1,2-dihydroxy or 1,2,3-trihydroxy groups.[54] Flavonoid configurations can also cause significant differences in sensory properties, e.g.epicatechin is more bitter and astringent than itschiralisomercatechin. In contrast, hydroxycinnamic acids do not have astringent qualities, but are bitter.[55]
Polyphenols are a large, diverse group of compounds, making it difficult to determine their biological effects.[56] They are not considerednutrients, as they are not used for growth, survival or reproduction, nor do they providedietary energy. Therefore, they do not have recommendeddaily intake levels, as exist forvitamins,minerals, andfiber.[57][58][59] In the United States, theFood and Drug Administration issued guidance to manufacturers that polyphenols cannot be mentioned onfood labels as antioxidant nutrients unlessphysiological evidence exists to verify such a qualification and a Dietary Reference Intake value has been established – characteristics which have not been determined for polyphenols.[60][61]
In theEuropean Union, twohealth claims were authorized between 2012 and 2015: 1) flavanols incocoa solids at doses exceeding 200 mg per day may contribute to maintenance of vascular elasticity and normal blood flow;[62][63] 2) olive oil polyphenols (5 mg ofhydroxytyrosol and its derivatives (e.g.oleuropein complex andtyrosol) may "contribute to the protection of blood lipids from oxidative damage", if consumed daily.[64][65]
As of 2022,clinical trials that assessed the effect of polyphenols on healthbiomarkers are limited, with results difficult to interpret due to the wide variation of intake values for both individual polyphenols and total polyphenols.[66]
Polyphenols were once considered asantioxidants, but this concept is obsolete.[67] Most polyphenols are metabolized bycatechol-O-methyltransferase, and therefore do not have the chemical structure allowing antioxidant activity in vivo; they may exert biological activity assignaling molecules.[2][61][68] Some polyphenols are considered to bebioactive compounds[69] for which development of dietary recommendations was under consideration in 2017.[70]
In the 1930s, polyphenols (then calledvitamin P) were considered as a factor incapillary permeability, followed by various studies through the 21st century of a possible effect on cardiovascular diseases. For most polyphenols, there is no evidence for an effect on cardiovascular regulation, although there are some reviews showing a minor effect of consuming polyphenols, such aschlorogenic acid orflavan-3-ols, on blood pressure.[71][72][73]
Higher intakes of soy isoflavones may be associated with reduced risks of breast cancer in postmenopausal women and prostate cancer in men.[2]
A 2019 systematic review found that intake of soy and soy isoflavones is associated with a lower risk ofmortality from gastric, colorectal, breast and lung cancers.[74] The study found that an increase in isoflavone consumption by 10 mg per day was associated with a 7% decrease in risk from all cancers, and an increase in consumption of soy protein by 5 grams per day produced a 12% reduction in breast cancer risk.[74]
Isoflavones, which are structurally related to17β-estradiol, are classified asphytoestrogens.[77] A risk assessment by the European Food Safety Authority found no cause for concern when isoflavones are consumed in a normal diet.[78]
Polyphenols are extensively metabolized by thegut microbiota and are investigated as a potential metabolic factor in function of the gut microbiota.[81][82]
Metabolism of polyphenols can result in flavonoid-drug interactions, such as ingrapefruit–drug interactions, which involves inhibition of the liverenzyme,CYP3A4, likely by grapefruitfuranocoumarins, a class of polyphenol.[2][83] The European Food Safety Authority established upper limits for some polyphenol-containing supplements and additives, such asgreen tea extract orcurcumin.[89][90] For most polyphenols found in the diet, an adverse effect beyond nutrient-drug interactions is unlikely.[2]
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