Raspberry ellagitannin, a tannin 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.
The term polyphenol is not well defined, but it is generally agreed that they are natural products "having a polyphenol structure (i.e., several hydroxyl groups on aromatic rings)" including four principal classes: "phenolic acids, flavonoids, stilbenes, and lignans".
Flavonoids include flavones, flavonols, flavanols, flavanones, isoflavones, proanthocyanidins, and anthocyanins. Particularly abundant flavanoids in foods are catechin (tea, fruits), hesperetin (citrus fruits), cyanidin (red fruits and berries), daidzein(soybean), proanthocyanidins (apple, grape, cocoa), and quercetin (onion, tea, apples).
The White-Bate-Smith-Swain-Haslam (WBSSH) definition characterized structural characteristics common to plant phenolics used in tanning (i.e., the tannins).
In terms of properties, the WBSSH describes the polyphenols thusly:
galloyl and hexahydroxydiphenoyl esters and their derivatives
Quideau definition of polyphenols
According to Stéphane Quideau the term "polyphenol" refers to compounds derived from the shikimate/phenylpropanoid and/or the polyketide pathway, featuring more than one phenolic unit and deprived of nitrogen-based functions.
Ellagic acid (M.W. 302, right), 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. The raspberry ellagitannin (M.W. ~2450), on the other hand, with its 14 gallic 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 the black teatheaflavin-3-gallate shown below, and the hydrolyzable tannin, tannic acid, shown above.
Polyphenols are often larger molecules (macromolecules). Their upper molecular weight limit is about 800 Daltons, 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 cell senesces. Hence, many larger polyphenols are biosynthesized in-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 by esters (hydrolyzable tannins) or more stable C-C bonds (nonhydrolyzable condensed tannins). Proanthocyanidins are mostly polymeric units of catechin and epicatechin.
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. The isoflavone and its 10-atom benzopyran "fused ring" system, also a structural feature here, is common in polyphenols.
Some polyphenols are traditionally used as dyes. For instance, in the Indian subcontinent, the pomegranatepeel, high in tannins and other polyphenols, or its juice, is employed in the dyeing of non-synthetic fabrics.
Polyphenols, especially tannins, were used traditionally for tanning leather and today also as precursors in green chemistry notably to produce plastics or resins by polymerisation with or without the use of formaldehyde or adhesives for particleboards. The aims are generally to make use of plant residues from grape, olive (called pomaces) or pecan shells left after processing.
Signaling molecules in ripening and other growth processes.
Occurrence in nature
The most abundant polyphenols are the condensed 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, and nutrient 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% total natural phenols and polyphenols, calculated with reference to the dry green leaf mass.
High levels of polyphenols in some woods can explain their natural preservation against rot.
Polyphenol oxidase (PPO) is an enzyme that catalyses the oxidation of o-diphenols to produce o-quinones. It is the rapid polymerisation of o-quinones to produce black, brown or red polyphenolic pigments that is the cause of fruit browning. In insects, PPO serves for the cuticle hardening.
Content in food
Polyphenols comprise up to 0.2-0.3% fresh weight for many fruits, grapes, and berries. Consuming common servings of wine, chocolate, legumes or tea may also contribute to about one gram of intake per day. 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.
In a comparison of cooking methods, phenolic and carotenoid levels in vegetables were retained better by steaming compared to frying. Polyphenols in wine, beer and various nonalcoholic juice beverages can be removed using finings, substances that are usually added at or near the completion of the processing of brewing.
Potential health effects
Although health effects may be attributed to polyphenols in food, the extensive metabolism of polyphenols in the intestine and liver, and their undefined fate as metabolites which are rapidly excreted in urine, prevents definition of their biological effects. Because the metabolism of polyphenols cannot be assessed in vivo, there are no Dietary Reference Intake (DRI) levels established or recommended.
In the US, the Food and Drug Administration (FDA) issued labeling guidance to manufacturers that polyphenols cannot be mentioned as antioxidant nutrients unless physiological evidence exists to verify such a qualification and a DRI value has been established. Furthermore, since purported health claims for specific polyphenol-enriched foods remain unproven, health statements about polyphenols on product labels are prohibited by the FDA and the EFSA. However, during the 21st century, the EFSA recognized certain health claims of specific polyphenol products, such as cocoa and olive oil.
Compared with the effects of polyphenols in vitro, the possible functions in vivo remain unknown due to 1) the absence of validated in vivo biomarkers; 2) long-term studies failing to demonstrate effects with a mechanism of action, sensitivity and specificity or efficacy; and 3) invalid applications of high, unphysiological test concentrations in the in vitro studies, which are subsequently irrelevant for the design of in vivo experiments.
With respect to food and beverages, the cause of astringency is not fully understood, but it is measured chemically as the ability of a substance to precipitate proteins.
A review published in 2005 found that astringency increases and bitterness decreases with the mean degree of polymerization. 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. Flavonoid configurations can also cause significant differences in sensory properties, e.g. epicatechin is more bitter and astringent than its chiralisomercatechin. In contrast, hydroxycinnamic acids do not have astringent qualities, but are bitter.
Mainly found in the fruit skins and seeds, high levels of polyphenols may reflect only the measured 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.
The DMACA reagent is an histological dye specific to polyphenols used in microscopy analyses. The autofluorescence of polyphenols can also be used, especially for localisation of lignin and suberin. 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 in plant science, to enhance the fluorescence signal.
Polyphenolic content can be quantified separation/isolation by volumetric titration. An oxidizing agent, permanganate, is used to oxidize known concentrations of a standard tannin solution, producing a standard curve. The tannin content of the unknown is then expressed as equivalents of the appropriate hydrolyzable or condensed tannin.
Some methods for quantification of total polyphenol content are based on colorimetric measurements. Some tests are relatively specific to polyphenols (for instance the Porter's assay). Total phenols (or antioxidant effect) can be measured using the Folin-Ciocalteu reaction. Results are typically expressed as gallic acid equivalents. Polyphenols are seldom evaluated by antibody technologies.
Other tests measure the antioxidant capacity of a fraction. Some make use of the ABTS radical cation which is reactive towards most antioxidants including phenolics, thiols and vitamin C. 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 the Trolox equivalent antioxidant capacity (TEAC) assay. The reactivity of the various antioxidants tested are compared to that of Trolox, which is a vitamin E analog.
New methods including the use of biosensors can help monitor the content of polyphenols in food.
Quantitation results produced by the mean of diode array detector-coupled HPLC are generally given as relative rather than absolute values as there is a lack of commercially available standards for all polyphenolic molecules.
The name derives from the Ancient Greek word (polus, meaning "many, much") and the word phenol which refers to a chemical structure formed by attaching to an aromatic benzenoid (phenyl) ring to a hydroxyl (-OH) group as is found in alcohols (hence the -ol suffix). The term polyphenol has been in use at least since 1894.
^ abQuideau, S. P.; Deffieux, D.; Douat-Casassus, C. L.; Pouységu, L. (2011). "Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis". Angewandte Chemie International Edition. 50 (3): 586-621. doi:10.1002/anie.201000044. PMID21226137.
^ abcdefg"Flavonoids". Micronutrient Information Center, Linus Pauling Institute, Oregon State University. 1 February 2016. Retrieved 2020.
^Santos, M.A; Bonilla Venceslada, J.L; Martin Martin, A; Garcia Garcia, I (2005). "Estimating the selectivity of ozone in the removal of polyphenols from vinasse". Journal of Chemical Technology and Biotechnology. 80 (4): 433-438. doi:10.1002/jctb.1222. INIST:16622840.
^Polshettiwar, Vivek; Varma, Rajender S. (2008). "Greener and expeditious synthesis of bioactive heterocycles using microwave irradiation". Pure and Applied Chemistry. 80 (4): 777-90. doi:10.1351/pac200880040777. S2CID11940026.
^Hillis, W. E.; Urbach, G. (1959). "Reaction of polyphenols with formaldehyde". Journal of Applied Chemistry. 9 (12): 665-673. doi:10.1002/jctb.5010091207.
^Pizzi, A.; Valenezuela, J.; Westermeyer, C. (1994). "Low formaldehyde emission, fast pressing, pine and pecan tannin adhesives for exterior particleboard". Holz Als Roh- und Werkstoff. 52 (5): 311-5. doi:10.1007/BF02621421. S2CID36500389.
^ abcdAizpurua-Olaizola, Oier; Ormazabal, Markel; Vallejo, Asier; Olivares, Maitane; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz (2015). "Optimization of Supercritical Fluid Consecutive Extractions of Fatty Acids and Polyphenols from Vitis Vinifera Grape Wastes". Journal of Food Science. 80 (1): E101-7. doi:10.1111/1750-3841.12715. PMID25471637.
^Hart, John H.; Hillis, W. E. (1974). "Inhibition of wood-rotting fungi by stilbenes and other polyphenols in Eucalyptus sideroxylon". Phytopathology. 64 (7): 939-48. doi:10.1094/Phyto-64-939.
^Popa, V; Dumitru, M; Volf, I; Anghel, N (2008). "Lignin and polyphenols as allelochemicals". Industrial Crops and Products. 27 (2): 144-9. doi:10.1016/j.indcrop.2007.07.019.
^Nakai, S (2000). "Myriophyllum spicatum-released allelopathic polyphenols inhibiting growth of blue-green algae Microcystis aeruginosa". Water Research. 34 (11): 3026-32. doi:10.1016/S0043-1354(00)00039-7.
^Wigglesworth, V. B. (1988). "The source of lipids and polyphenols for the insect cuticle: The role of fat body, oenocytes and oenocytoids". Tissue and Cell. 20 (6): 919-932. doi:10.1016/0040-8166(88)90033-X. PMID18620248.
^Krasnow, M. N.; Murphy, T. M. (2004). "Polyphenol Glucosylating Activity in Cell Suspensions of Grape (Vitis vinifera)". Journal of Agricultural and Food Chemistry. 52 (11): 3467-3472. doi:10.1021/jf035234r. PMID15161217.
^Malek, S. R. A. (1961). "Polyphenols and their quinone derivatives in the cuticle of the desert locust, Schistocerca gregaria (Forskål)". Comparative Biochemistry and Physiology. 2: 35-77. doi:10.1016/0010-406X(61)90071-8.
^Hufnagel JC, Hofmann T (2008). "Orosensory-directed identification of astringent mouthfeel and bitter-tasting compounds in red wine". J Agric Food Chem. 56 (4): 1376-1386. doi:10.1021/jf073031n. PMID18193832.
^Owen, R. W.; Haubner, R.; Hull, W. E.; Erben, G.; Spiegelhalder, B.; Bartsch, H.; Haber, B. (2003). "Isolation and structure elucidation of the major individual polyphenols in carob fibre". Food and Chemical Toxicology. 41 (12): 1727-1738. doi:10.1016/S0278-6915(03)00200-X. PMID14563398.
^Alonsosalces, R; Korta, E; Barranco, A; Berrueta, L; Gallo, B; Vicente, F (2001). "Pressurized liquid extraction for the determination of polyphenols in apple". Journal of Chromatography A. 933 (1-2): 37-43. doi:10.1016/S0021-9673(01)01212-2. PMID11758745.
^Sineiro, J.; Domínguez, H.; Núñez, M. J.; Lema, J. M. (1996). "Ethanol extraction of polyphenols in an immersion extractor. Effect of pulsing flow". Journal of the American Oil Chemists' Society. 73 (9): 1121-5. doi:10.1007/BF02523372. S2CID96009875.
^Arranz, Sara; Saura-Calixto, Fulgencio; Shaha, Shika; Kroon, Paul A. (2009). "High Contents of Nonextractable Polyphenols in Fruits Suggest That Polyphenol Contents of Plant Foods Have Been Underestimated". Journal of Agricultural and Food Chemistry. 57 (16): 7298-303. doi:10.1021/jf9016652. hdl:10261/82508. PMID19637929.
^Nawaz, H; Shi, J; Mittal, G; Kakuda, Y (2006). "Extraction of polyphenols from grape seeds and concentration by ultrafiltration". Separation and Purification Technology. 48 (2): 176-81. doi:10.1016/j.seppur.2005.07.006.
^Gani, M.; McGuinness, B. J.; Da Vies, A. P. (1998). "Monoclonal antibodies against tea polyphenols: A novel immunoassay to detect polyphenols in biological fluids". Food and Agricultural Immunology. 10: 13-22. doi:10.1080/09540109809354964.
^Walker, Richard B.; Everette, Jace D. (2009). "Comparative Reaction Rates of Various Antioxidants with ABTS Radical Cation". Journal of Agricultural and Food Chemistry. 57 (4): 1156-61. doi:10.1021/jf8026765. PMID19199590.
^Roy, Molay K; Koide, Motoki; Rao, Theertham P; Okubo, Tsutomu; Ogasawara, Yutaka; Juneja, Lekh R (2010). "ORAC and DPPH assay comparison to assess antioxidant capacity of tea infusions: Relationship between total polyphenol and individual catechin content". International Journal of Food Sciences and Nutrition. 61 (2): 109-24. doi:10.3109/09637480903292601. PMID20109129. S2CID1929167.
^Pulido, R.; Bravo, L.; Saura-Calixto, F. (2000). "Antioxidant Activity of Dietary Polyphenols As Determined by a Modified Ferric Reducing/Antioxidant Power Assay". Journal of Agricultural and Food Chemistry. 48 (8): 3396-3402. doi:10.1021/jf9913458. hdl:10261/112476. PMID10956123.
^Meyer, A. S.; Yi, O. S.; Pearson, D. A.; Waterhouse, A. L.; Frankel, E. N. (1997). "Inhibition of Human Low-Density Lipoprotein Oxidation in Relation to Composition of Phenolic Antioxidants in Grapes (Vitis vinifera)". Journal of Agricultural and Food Chemistry. 45 (5): 1638-1643. doi:10.1021/jf960721a.
^Mello, L; Sotomayor, Maria Del Pilar Taboada; Kubota, Lauro Tatsuo (2003). "HRP-based amperometric biosensor for the polyphenols determination in vegetables extract". Sensors and Actuators B: Chemical. 96 (3): 636-45. doi:10.1016/j.snb.2003.07.008.