Flavonoid

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Molecular structure of the flavone backbone (2-phenyl-1,4-benzopyrone)
Isoflavan structure
Neoflavonoids structure

Flavonoids (or bioflavonoids; from the Latin word flavus, meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in diets.[1]

Chemically, flavonoids have the general structure of a 15-carbon skeleton, which consists of two phenyl rings (A and B) and a heterocyclic ring (C).[1] This carbon structure can be abbreviated C6-C3-C6. According to the IUPAC nomenclature,[2][3] they can be classified into:

The three flavonoid classes above are all ketone-containing compounds and as such, anthoxanthins (flavones and flavonols).[1] This class was the first to be termed bioflavonoids. The terms flavonoid and bioflavonoid have also been more loosely used to describe non-ketone polyhydroxy polyphenol compounds, which are more specifically termed flavanoids. The three cycles or heterocycles in the flavonoid backbone are generally called ring A, B, and C. Ring A usually shows a phloroglucinol substitution pattern.

Biosynthesis[edit]

Flavonoids are secondary metabolites synthesized mainly by plants. The general structure of flavonoids is a 15-carbon skeleton, containing 2 benzene rings connected by a 3-carbon linking chain.[1] Therefore, they are depicted as C6-C3-C6 compounds. Depending on the chemical structure, degree of oxidation, and unsaturation of the linking chain (C3), flavonoids can be classified into different groups, such as anthocyanidins, chalcones, flavonols, flavanones, flavan-3-ols, flavanonols, flavones, and isoflavonoids.[1] Furthermore, flavonoids can be found in plants in glycoside-bound and free aglycone forms. The glycoside-bound form is the most common flavone and flavonol form consumed in the diet.[1]

Functions of flavonoids in plants[edit]

Flavonoids are widely distributed in plants, fulfilling many functions. [1] Flavonoids are the most important plant pigments for flower coloration, producing yellow or red/blue pigmentation in petals designed to attract pollinator animals. In higher plants, flavonoids are involved in UV filtration, symbiotic nitrogen fixation and floral pigmentation. They may also act as chemical messengers, physiological regulators, and cell cycle inhibitors. Flavonoids secreted by the root of their host plant help Rhizobia in the infection stage of their symbiotic relationship with legumes like peas, beans, clover, and soy. Rhizobia living in soil are able to sense the flavonoids and this triggers the secretion of Nod factors, which in turn are recognized by the host plant and can lead to root hair deformation and several cellular responses such as ion fluxes and the formation of a root nodule. In addition, some flavonoids have inhibitory activity against organisms that cause plant diseases, e.g. Fusarium oxysporum.[4]

Subgroups[edit]

Over 5000 naturally occurring flavonoids have been characterized from various plants. They have been classified according to their chemical structure, and are usually subdivided into the following subgroups (for further reading see[5]):

Anthocyanidins[edit]

Flavylium skeleton of anthocyanidins

Anthocyanidins are the aglycones of anthocyanins; they use the flavylium (2-phenylchromenylium) ion skeleton.[1]

Anthoxanthins[edit]

Anthoxanthins are divided into two groups:[6]

Group Skeleton Examples
Description Functional groups Structural formula
3-hydroxyl 2,3-dihydro
Flavone 2-phenylchromen-4-one Flavone skeleton colored.svg Luteolin, Apigenin, Tangeritin
Flavonol
or
3-hydroxyflavone
3-hydroxy-2-phenylchromen-4-one Flavonol skeleton colored.svg Quercetin, Kaempferol, Myricetin, Fisetin, Galangin, Isorhamnetin, Pachypodol, Rhamnazin, Pyranoflavonols, Furanoflavonols,

Flavanones[edit]

Flavanones

Group Skeleton Examples
Description Functional groups Structural formula
3-hydroxyl 2,3-dihydro
Flavanone 2,3-dihydro-2-phenylchromen-4-one Flavanone skeleton colored.svg Hesperetin, Naringenin, Eriodictyol, Homoeriodictyol

Flavanonols[edit]

Flavanonols

Group Skeleton Examples
Description Functional groups Structural formula
3-hydroxyl 2,3-dihydro
Flavanonol
or
3-Hydroxyflavanone
or
2,3-dihydroflavonol
3-hydroxy-2,3-dihydro-2-phenylchromen-4-one Flavanonol skeleton colored.svg Taxifolin (or Dihydroquercetin), Dihydrokaempferol

Flavans[edit]

Flavan structure

Include flavan-3-ols (flavanols), flavan-4-ols and flavan-3,4-diols.

Skeleton Name
Flavan-3ol Flavan-3-ol (flavanol)
Flavan-4ol Flavan-4-ol
Flavan-3,4-diol Flavan-3,4-diol (leucoanthocyanidin)

Isoflavonoids[edit]

Dietary sources[edit]

Parsley is a source of flavones.
Blueberries are a source of dietary anthocyanidins.
A variety of flavonoids are found in citrus fruits, including grapefruit.

Flavonoids (specifically flavanoids such as the catechins) are "the most common group of polyphenolic compounds in the human diet and are found ubiquitously in plants".[1][7] Flavonols, the original bioflavonoids such as quercetin, are also found ubiquitously, but in lesser quantities. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet.[1] Foods with a high flavonoid content include parsley,[8] onions,[8] blueberries and other berries,[8] black tea,[8] green tea and oolong tea,[8] bananas, all citrus fruits, Ginkgo biloba, red wine, sea-buckthorns, buckwheat,[9] and dark chocolate with a cocoa content of 70% or greater.

Parsley[edit]

Parsley, both fresh and dried, contains flavones.[8]

Blueberries[edit]

Blueberries are a dietary source of anthocyanidins.[8][10]

Black tea[edit]

Black tea is a rich source of dietary flavan-3-ols.[8]

Citrus[edit]

The citrus flavonoids include hesperidin (a glycoside of the flavanone hesperetin), quercitrin, rutin (two glycosides of the flavonol quercetin), and the flavone tangeritin. The flavonoids are much less concentrated in the pulp than in the peels (for example, 165 vs. 1156 mg/100g in pulp vs. peel of satsuma mandarin, and 164 vs 804 mg/100g in pulp vs. peel of clementine).[11]

Wine[edit]

Cocoa[edit]

Flavonoids exist naturally in cocoa, but because they can be bitter, they are often removed from chocolate, even dark chocolate.[12] Although flavonoids are present in milk chocolate, milk may interfere with their absorption;[13][14] however this conclusion has been questioned.[15]

Peanut[edit]

Peanut (red) skin contains significant polyphenol content, including flavonoids.[16][17]

Food source Flavones Flavonols Flavanones
Red onion 0 4 - 100 0
Parsley, fresh 24 - 634 8 - 10 0
Thyme, fresh 56 0 0
Lemon juice, fresh 0 0 - 2 2 - 175

Unit: mg/100g[1]

Dietary intake[edit]

Mean flavonoid intake in mg/d per country, the pie charts show the relative contribution of different types of flavonoids.[18]

Food composition data for flavonoids were provided by the USDA database on flavonoids.[8] In the United States NHANES survey, mean flavonoid intake was 190 mg/d in adults, with flavan-3-ols as the main contributor.[19] In the European Union, based on data from EFSA, mean flavonoid intake was 140 mg/d, although there were considerable differences between individual countries.[18]

Data is based on mean flavonoid intake of all countries included in the 2011 EFSA Comprehensive European Food Consumption Database.[18]

The main type of flavonoids consumed in the EU and USA were flavan-3-ols, mainly from tea, while intake of other flavonoids was considerably lower.[18][19]

Research[edit]

Neither the Food and Drug Administration (FDA) nor the European Food Safety Authority (EFSA) has approved any health claim for flavonoids or approved any flavonoids as prescription drugs.[1][20][21][22] The US FDA has warned numerous dietary supplement companies about illegal advertising and misleading health claims.[23][24]

Metabolism and excretion[edit]

Flavonoids are poorly absorbed in the human body (less than 5%), then are quickly metabolized into smaller fragments with unknown properties, and rapidly excreted.[1][22][25][26] Flavonoids have negligible antioxidant activity in the body, and the increase in antioxidant capacity of blood seen after consumption of flavonoid-rich foods is not caused directly by flavonoids, but is due to production of uric acid resulting from flavonoid depolymerization and excretion.[1][27]

Inflammation[edit]

Inflammation has been implicated as a possible origin of numerous local and systemic diseases, such as cancer,[28] cardiovascular disorders,[29] diabetes mellitus,[30] and celiac disease.[31] There is no clinical evidence that dietary flavonoids affect any of these diseases.[1]

Cancer[edit]

Clinical studies investigating the relationship between flavonoid consumption and cancer prevention/development are conflicting for most types of cancer, probably because most human studies have weak designs, such as a small sample size.[1][32] There is little evidence to indicate that dietary flavonoids affect human cancer risk.[1]

Cardiovascular diseases[edit]

Among the most extensively studied of general human disorders possibly affected by dietary flavonoids, research on cardiovascular disease has not provided sufficient evidence of an effect of flavonoids, as of 2016.[1] Reviews of cohort studies in 2013 found that the studies had too many limitations to determine a possible relationship between increased flavonoid intake and decreased risk of cardiovascular disease, although a trend for an inverse relationship existed.[1][33]

In vitro[edit]

Laboratory studies indicate that flavonoids have effects on isolated cells or cell cultures in vitro, but there is no such evidence from human clinical research.[1]

Synthesis, detection, quantification, and semi-synthetic alterations[edit]

Color spectrum[edit]

Flavonoid synthesis in plants is induced by light color spectrums at both high and low energy radiations. Low energy radiations are accepted by phytochrome, while high energy radiations are accepted by carotenoids, flavins, cryptochromes in addition to phytochromes. The photomorphogenic process of phytochrome-mediated flavonoid biosynthesis has been observed in Amaranthus, barley, maize, Sorghum and turnip. Red light promotes flavonoid synthesis.[34]

Availability through microorganisms[edit]

Several recent research articles have demonstrated the efficient production of flavonoid molecules from genetically engineered microorganisms.[35][36][37] and the project SynBio4Flav[38][39] aims to provide a cost-effective alternative to current flavonoid production breaking down their complex biosynthetic pathways into standardized specific parts, which can be transferred to engineered microorganisms within Synthetic Microbial Consortia to promote flavonoid assembly through distributed catalysis.

Tests for detection[edit]

Shinoda test

Four pieces of magnesium filings are added to the ethanolic extract followed by few drops of concentrated hydrochloric acid. A pink or red colour indicates the presence of flavonoid.[40] Colours varying from orange to red indicated flavones, red to crimson indicated flavonoids, crimson to magenta indicated flavonones.

Sodium hydroxide test

About 5 mg of the compound is dissolved in water, warmed and filtered. 10% aqueous sodium hydroxide is added to 2 ml of this solution. This produces a yellow coloration. A change in color from yellow to colorless on addition of dilute hydrochloric acid is an indication for the presence of flavonoids.[41]

p-Dimethylaminocinnamaldehyde test

A colorimetric assay based upon the reaction of A-rings with the chromogen p-dimethylaminocinnamaldehyde (DMACA) has been developed for flavanoids in beer that can be compared with the vanillin procedure.[42]

Quantification[edit]

Lamaison and Carnet have designed a test for the determination of the total flavonoid content of a sample (AlCI3 method). After proper mixing of the sample and the reagent, the mixture is incubated for 10 minutes at ambient temperature and the absorbance of the solution is read at 440 nm. Flavonoid content is expressed in mg/g of quercetin.[43]

Semi-synthetic alterations[edit]

Immobilized Candida antarctica lipase can be used to catalyze the regioselective acylation of flavonoids.[44]

See also[edit]

References[edit]

  1. ^ a b c d e f g h i j k l m n o p q r s t "Flavonoids". Linus Pauling Institute, Oregon State University, Corvallis, OR. 2020. Retrieved 6 October 2020.
  2. ^ McNaught, Alan D; Wilkinson, Andrew; IUPAC (1997), IUPAC Compendium of Chemical Terminology (2 ed.), Oxford: Blackwell Scientific, doi:10.1351/goldbook.F02424, ISBN 978-0-9678550-9-7
  3. ^ Nič, Miloslav; Jirát, Jiří; Košata, Bedřich; Jenkins, Aubrey; McNaught, Alan, eds. (2009). "Flavonoids (isoflavonoids and neoflavonoids)". The Gold Book. doi:10.1351/goldbook. ISBN 978-0-9678550-9-7. Retrieved 16 September 2012.
  4. ^ Galeotti, F; Barile, E; Curir, P; Dolci, M; Lanzotti, V (2008). "Flavonoids from carnation (Dianthus caryophyllus) and their antifungal activity". Phytochemistry Letters. 1: 44–48. doi:10.1016/j.phytol.2007.10.001.
  5. ^ Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (October 2007). "Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health". Biotechnology Journal. 2 (10): 1214–34. doi:10.1002/biot.200700084. PMID 17935117.
  6. ^ Isolation of a UDP-glucose: Flavonoid 5-O-glucosyltransferase gene and expression analysis of anthocyanin biosynthetic genes in herbaceous peony (Paeonia lactiflora Pall.). Da Qiu Zhao, Chen Xia Han, Jin Tao Ge and Jun Tao, Electronic Journal of Biotechnology, 15 November 2012, Volume 15, Number 6, doi:10.2225/vol15-issue6-fulltext-7
  7. ^ Spencer JP (2008). "Flavonoids: modulators of brain function?". British Journal of Nutrition. 99 (E-S1): ES60–77. doi:10.1017/S0007114508965776. PMID 18503736.
  8. ^ a b c d e f g h i USDA’s Database on the Flavonoid Content
  9. ^ Oomah, B. Dave; Mazza, Giuseppe (1996). "Flavonoids and Antioxidative Activities in Buckwheat". Journal of Agricultural and Food Chemistry. 44 (7): 1746–1750. doi:10.1021/jf9508357.
  10. ^ Ayoub M, de Camargo AC, Shahidi F (2016). "Antioxidants and bioactivities of free, esterified and insoluble-bound phenolics from berry seed meals". Food Chemistry. 197 (Part A): 221–232. doi:10.1016/j.foodchem.2015.10.107. PMID 26616944.
  11. ^ [1] p. 223 Table 1
  12. ^ The Lancet (2007). "The devil in the dark chocolate". Lancet. 370 (9605): 2070. doi:10.1016/S0140-6736(07)61873-X. PMID 18156011.
  13. ^ Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A (2003). "Plasma antioxidants from chocolate" (PDF). Nature. 424 (6952): 1013. Bibcode:2003Natur.424.1013S. doi:10.1038/4241013a. PMID 12944955.
  14. ^ Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A (2003). "Nutrition: milk and absorption of dietary flavanols" (PDF). Nature. 424 (6952): 1013. Bibcode:2003Natur.424.1013S. doi:10.1038/4241013a. PMID 12944955.
  15. ^ Roura E, et al. (2007). "Milk Does Not Affect the Bioavailability of Cocoa Powder Flavonoid in Healthy Human" (PDF). Ann Nutr Metab. 51 (6): 493–498. doi:10.1159/000111473. PMID 18032884.[permanent dead link]
  16. ^ de Camargo AC, Regitano-d'Arce MA, Gallo CR, Shahidi F (2015). "Gamma-irradiation induced changes in microbiological status, phenolic profile and antioxidant activity of peanut skin". Journal of Functional Foods. 12: 129–143. doi:10.1016/j.jff.2014.10.034.
  17. ^ Chukwumah Y, Walker LT, Verghese M (2009). "Peanut skin color: a biomarker for total polyphenolic content and antioxidative capacities of peanut cultivars". Int J Mol Sci. 10 (11): 4941–52. doi:10.3390/ijms10114941. PMC 2808014. PMID 20087468.
  18. ^ a b c d Vogiatzoglou, A; Mulligan, A. A.; Lentjes, M. A.; Luben, R. N.; Spencer, J. P.; Schroeter, H; Khaw, K. T.; Kuhnle, G. G. (2015). "Flavonoid intake in European adults (18 to 64 years)". PLOS ONE. 10 (5): e0128132. doi:10.1371/journal.pone.0128132. PMC 4444122. PMID 26010916.
  19. ^ a b Chun, O. K.; Chung, S. J.; Song, W. O. (2007). "Estimated dietary flavonoid intake and major food sources of U.S. Adults". The Journal of Nutrition. 137 (5): 1244–52. doi:10.1093/jn/137.5.1244. PMID 17449588.
  20. ^ "FDA approved drug products". US Food and Drug Administration. Retrieved 8 November 2013.
  21. ^ "Health Claims Meeting Significant Scientific Agreement". US Food and Drug Administration. Retrieved 8 November 2013.
  22. ^ a b EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2010). "Scientific Opinion on the substantiation of health claims related to various food(s)/food constituent(s) and protection of cells from premature aging, antioxidant activity, antioxidant content and antioxidant properties, and protection of DNA, proteins and lipids from oxidative damage pursuant to Article 13(1) of Regulation (EC) No 1924/20061". EFSA Journal. 8 (2): 1489. doi:10.2903/j.efsa.2010.1489.
  23. ^ "Inspections, Compliance, Enforcement, and Criminal Investigations (Flavonoid Sciences)". US Food and Drug Administration. Retrieved 8 November 2013.
  24. ^ "Inspections, Compliance, Enforcement, and Criminal Investigations (Unilever, Inc.)". US Food and Drug Administration. Retrieved 25 October 2013.
  25. ^ Lotito SB, Frei B (2006). "Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon?". Free Radic. Biol. Med. 41 (12): 1727–46. doi:10.1016/j.freeradbiomed.2006.04.033. PMID 17157175.
  26. ^ Williams RJ, Spencer JP, Rice-Evans C (2004). "Flavonoids: antioxidants or signalling molecules?". Free Radical Biology & Medicine. 36 (7): 838–49. doi:10.1016/j.freeradbiomed.2004.01.001. PMID 15019969.
  27. ^ Stauth D (5 March 2007). "Studies force new view on biology of flavonoids". EurekAlert!, Adapted from a news release issued by Oregon State University.
  28. ^ Ravishankar D, Rajora AK, Greco F, Osborn HM (2013). "Flavonoids as prospective compounds for anti-cancer therapy". The International Journal of Biochemistry & Cell Biology. 45 (12): 2821–2831. doi:10.1016/j.biocel.2013.10.004. PMID 24128857.
  29. ^ Manach C, Mazur A, Scalbert A (2005). "Polyphenols and prevention of cardiovascular diseases". Current Opinion in Lipidology. 16 (1): 77–84. doi:10.1097/00041433-200502000-00013. PMID 15650567.
  30. ^ Babu PV, Liu D, Gilbert ER (2013). "Recent advances in understanding the anti-diabetic actions of dietary flavonoids". The Journal of Nutritional Biochemistry. 24 (11): 1777–1789. doi:10.1016/j.jnutbio.2013.06.003. PMC 3821977. PMID 24029069.
  31. ^ Ferretti G, Bacchetti T, Masciangelo S, Saturni L (2012). "Celiac Disease, Inflammation and Oxidative Damage: A Nutrigenetic Approach". Nutrients. 4 (12): 243–257. doi:10.3390/nu4040243. PMC 3347005. PMID 22606367.
  32. ^ Romagnolo DF, Selmin OI (2012). "Flavonoids and cancer prevention: a review of the evidence". J Nutr Gerontol Geriatr. 31 (3): 206–38. doi:10.1080/21551197.2012.702534. PMID 22888839.
  33. ^ Wang X; Ouyang YY; Liu J; Zhao G (January 2014). "Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies". The British Journal of Nutrition. 111 (1): 1–11. doi:10.1017/S000711451300278X. PMID 23953879.
  34. ^ Sinha, Rajiv Kumar (2004-01-01). Modern Plant Physiology. CRC Press. p. 457. ISBN 9780849317149.
  35. ^ Hwang EI, Kaneko M, Ohnishi Y, Horinouchi S (May 2003). "Production of plant-specific flavanones by Escherichia coli containing an artificial gene cluster". Appl. Environ. Microbiol. 69 (5): 2699–706. doi:10.1128/AEM.69.5.2699-2706.2003. PMC 154558. PMID 12732539.
  36. ^ Trantas E, Panopoulos N, Ververidis F (2009). "Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae". Metabolic Engineering. 11 (6): 355–366. doi:10.1016/j.ymben.2009.07.004. PMID 19631278.
  37. ^ Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (2007). "Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part II: Reconstruction of multienzyme pathways in plants and microbes". Biotechnology Journal. 2 (10): 1235–49. doi:10.1002/biot.200700184. PMID 17935118.
  38. ^ "SynBio4Flav | boosting the standardization of high complexity synthetic biological parts". synbio4flav.eu. Retrieved 2020-11-16.
  39. ^ "Synthetic microbial consortia-based platform for flavonoids production using synthetic biology | H2020 | European Commission".
  40. ^ Yisa, Jonathan (2009). "Phytochemical Analysis and Antimicrobial Activity Of Scoparia Dulcis and Nymphaea Lotus". Australian Journal of Basic and Applied Sciences. 3 (4): 3975–3979. Archived from the original on 2013-10-17.
  41. ^ Bello IA, Ndukwe GI, Audu OT, Habila JD (2011). "A bioactive flavonoid from Pavetta crassipes K. Schum". Organic and Medicinal Chemistry Letters. 1 (1): 14. doi:10.1186/2191-2858-1-14. PMC 3305906. PMID 22373191.
  42. ^ Delcour JA (1985). "A New Colourimetric Assay for Flavanoids in Pilsner Beers". Journal of the Institute of Brewing. 91: 37–40. doi:10.1002/j.2050-0416.1985.tb04303.x.
  43. ^ Lamaison, JL; Carnet, A (1991). "Teneurs en principaux flavonoides des fleurs de Cratageus monogyna Jacq et de Cratageus Laevigata (Poiret D.C) en Fonction de la vegetation". Plantes Medicinales Phytotherapie. 25: 12–16.
  44. ^ Passicos E, Santarelli X, Coulon D (2004). "Regioselective acylation of flavonoids catalyzed by immobilized Candida antarctica lipase under reduced pressure". Biotechnol. Lett. 26 (13): 1073–1076. doi:10.1023/B:BILE.0000032967.23282.15. PMID 15218382.

Further reading[edit]

  • Andersen, Ø.M. / Markham, K.R. (2006). Flavonoids: Chemistry, Biochemistry and Applications. CRC Press. ISBN 978-0-8493-2021-7
  • Grotewold, Erich (2007). The Science of Flavonoids. Springer. ISBN 978-0-387-74550-3
  • Comparative Biochemistry of the Flavonoids, by J.B. Harborne, 1967 (Google Books)
  • l.a.g (1971). "The systematic identification of flavonoids". Journal of Molecular Structure. 10 (2): 320. doi:10.1016/0022-2860(71)87109-0.

Databases[edit]