Flavan-3-ol

Last updated

Chemical structure of flavan-3-ol Flavan-3-ol.svg
Chemical structure of flavan-3-ol

Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compounds, such as catechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, proanthocyanidins, theaflavins, thearubigins. They play a part in plant defense and are present in the majority of plants. [1]

Contents

Chemical structure

The single-molecule (monomer) catechin, or isomer epicatechin (see diagram), adds four hydroxyls to flavan-3-ol, making building blocks for concatenated polymers (proanthocyanidins) and higher order polymers (anthocyanidins). [2]

Flavan-3-ols possess two chiral carbons, meaning four diastereoisomers occur for each of them. They are distinguished from the yellow, ketone-containing flavonoids such as quercitin and rutin, which are called flavonols. Early use of the term bioflavonoid was imprecisely applied to include the flavanols, which are distinguished by absence of ketone(s). Catechin monomers, dimers, and trimers (oligomers) are colorless. Higher order polymers, anthocyanidins, exhibit deepening reds and become tannins. [2]

Catechin and epicatechin are epimers, with (–)-epicatechin and (+)-catechin being the most common optical isomers found in nature. Catechin was first isolated from the plant extract catechu, from which it derives its name. Heating catechin past its point of decomposition releases pyrocatechol (also called catechol), which explains the common origin of the names of these compounds.

Epigallocatechin and gallocatechin contain an additional phenolic hydroxyl group when compared to epicatechin and catechin, respectively, similar to the difference in pyrogallol compared to pyrocatechol.

Catechin gallates are gallic acid esters of the catechins; an example is epigallocatechin gallate, which is commonly the most abundant catechin in tea. Proanthocyanidins and thearubigins are oligomeric flavan-3-ols.

In contrast to many other flavonoids, flavan-3-ols do not generally exist as glycosides in plants. [3]

Structures (Epi)catechin, (epi)catechin-gallate, (epi)gallocatechin and (epi)gallocatechin-gallate. Catechin molecule file.png
Structures (Epi)catechin, (epi)catechin-gallate, (epi)gallocatechin and (epi)gallocatechin-gallate.

Biosynthesis of (–)-epicatechin

The flavonoids are products from a cinnamoyl-CoA starter unit, with chain extension using three molecules of malonyl-CoA. Reactions are catalyzed by a type III PKS enzyme. These enzyme do not use ACPSs, but instead employ coenzyme A esters and have a single active site to perform the necessary series of reactions, e.g. chain extension, condensation, and cyclization. Chain extension of 4-hydroxycinnamoyl-CoA with three molecules of malonyl-CoA gives initially a polyketide (Figure 1), which can be folded. These allow Claisen-like reactions to occur, generating aromatic rings. [4] [5] Fluorescence-lifetime imaging microscopy (FLIM) can be used to detect flavanols in plant cells. [6]

Figure 1 Epicatechin Biosynthesis-2.png
Figure 1

Figure 1:Schematic overview of the flavan-3-ol (–)-epicatechin biosynthesis in plants: Enzymes are indicated in blue, abbreviated as follows: E1, phenylalanine ammonia lyase (PAL), E2, tyrosine ammonia lyase (TAL), E3, cinnamate 4-hydroxylase, E4, 4-coumaroyl: CoA-ligase, E5, chalcone synthase (naringenin-chalcone synthase), E6, chalcone isomerase, E7, Flavonoid 3'-hydroxylase, E8, flavonone 3-hydroxylase, E9, dihydroflavanol 4-reductase, E10, anthocyanidin synthase (leucoanthocyanidin dioxygenase), E11, anthocyanidin reductase. HSCoA, Coenzyme A. L-Tyr, L-tyrosine, L-Phe, L-phenylalanine.

Aglycones

Flavan-3-ols
ImageNameFormulaOligomers
(+)-Catechin.svg Catechin, C, (+)-CatechinC15H14O6 Procyanidins
(-)-Epicatechin.svg Epicatechin, EC, (–)-Epicatechin (cis)C15H14O6 Procyanidins
Epigallocatechin.svg Epigallocatechin, EGCC15H14O7 Prodelphinidins
Epicatechin gallate.svg Epicatechin gallate, ECGC22H18O10
Epigallocatechin gallate structure.svg Epigallocatechin gallate, EGCG,
(–)-Epigallocatechin gallate
C22H18O11
Epiafzelechin.svg Epiafzelechin C15H14O5
Fisetinidol.svg Fisetinidol C15H14O5
Guibourtinidol.svg Guibourtinidol C15H14O4 Proguibourtinidins
Mesquitol.svg Mesquitol C15H14O6
Robinetinidol.svg Robinetinidol C15H14O6 Prorobinetinidins

Dietary sources

Reported range of flavan-3-ol content in foods commonly consumed. Variability of flavan-3-ol content in foods.png
Reported range of flavan-3-ol content in foods commonly consumed.

Flavan-3-ols are abundant in teas derived from the tea plant Camellia sinensis , as well as in some cocoas (made from the seeds of Theobroma cacao ), although the content is affected considerably by processing, especially in chocolate. [8] [9] Flavan-3-ols are also present in the human diet in fruits, in particular pome fruits, berries, vegetables, and wine. [10] Their content in food is variable and affected by various factors, such as cultivar, processing, and preparation. [11]

Bioavailability and metabolism

The bioavailability of flavan-3-ols depends on the food matrix, type of compound and their stereochemical configuration. [12] While monomeric flavan-3-ols are readily taken up, oligomeric forms are not absorbed. [12] [13] Most data for human metabolism of flavan-3-ols are available for monomeric compounds, especially epiatechin. These compounds are taken up and metabolized upon uptake in the jejunum, [14] mainly by O-methylation and glucuronidation, [15] and then further metabolized by the liver. The colonic microbiome has also an important role in the metabolism of flavan-3-ols and they are catabolized to smaller compounds such as 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones and hippuric acid. [16] [17] Only flavan-3-ols with an intact (epi)catechin moiety can be metabolized into 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones (image in Gallery). [18]

Possible adverse effects

As catechins in green tea extract can be hepatotoxic, Health Canada and EFSA have advised for caution, [19] recommending intake should not exceed 800 mg per day. [20]

Research

Research has shown that flavan-3-ols may affect vascular function, blood pressure, and blood lipids, with only minor effects demonstrated, as of 2019. [21] [22] In 2015, the European Commission approved a health claim for cocoa solids containing 200 mg of flavanols, stating that such intake "may contribute to maintenance of vascular elasticity and normal blood flow". [23] [24] As of 2022, food-based evidence indicates that intake of 400–600 mg per day of flavan-3-ols could have a small positive effect on cardiovascular biomarkers. [25]

Related Research Articles

<span class="mw-page-title-main">Gallic acid</span> 3,4,5-Trihydroxybenzoic acid

Gallic acid (also known as 3,4,5-trihydroxybenzoic acid) is a trihydroxybenzoic acid with the formula C6H2(OH)3CO2H. It is classified as a phenolic acid. It is found in gallnuts, sumac, witch hazel, tea leaves, oak bark, and other plants. It is a white solid, although samples are typically brown owing to partial oxidation. Salts and esters of gallic acid are termed "gallates".

<span class="mw-page-title-main">Flavonoid</span> Class of plant and fungus secondary metabolites

Flavonoids are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans.

<span class="mw-page-title-main">Polyphenol</span> Class of chemical compounds

Polyphenols are a large family of naturally occurring phenols. They are abundant in plants and structurally diverse. Polyphenols include flavonoids, tannic acid, and ellagitannin, some of which have been used historically as dyes and for tanning garments.

<span class="mw-page-title-main">Phytochemical</span> Chemical compounds produced by plants

Phytochemicals are chemical compounds produced by plants, generally to help them resist fungi, bacteria and plant virus infections, and also consumption by insects and other animals. The name comes from Greek φυτόν (phyton) 'plant'. Some phytochemicals have been used as poisons and others as traditional medicine.

<span class="mw-page-title-main">Catechin</span> Type of natural phenol as a plant secondary metabolite

Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids.

Proanthocyanidins are a class of polyphenols found in many plants, such as cranberry, blueberry, and grape seeds. Chemically, they are oligomeric flavonoids. Many are oligomers of catechin and epicatechin and their gallic acid esters. More complex polyphenols, having the same polymeric building block, form the group of tannins.

<span class="mw-page-title-main">Epigallocatechin gallate</span> Catechin (polyphenol) in tea

Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin.

<span class="mw-page-title-main">Gallocatechol</span> Chemical compound

Gallocatechol or gallocatechin (GC) is a flavan-3-ol, a type of chemical compound including catechin, with the gallate residue being in an isomeric trans position.

<span class="mw-page-title-main">Phenolic content in wine</span> Wine chemistry

The phenolic content in wine refers to the phenolic compounds—natural phenol and polyphenols—in wine, which include a large group of several hundred chemical compounds that affect the taste, color and mouthfeel of wine. These compounds include phenolic acids, stilbenoids, flavonols, dihydroflavonols, anthocyanins, flavanol monomers (catechins) and flavanol polymers (proanthocyanidins). This large group of natural phenols can be broadly separated into two categories, flavonoids and non-flavonoids. Flavonoids include the anthocyanins and tannins which contribute to the color and mouthfeel of the wine. The non-flavonoids include the stilbenoids such as resveratrol and phenolic acids such as benzoic, caffeic and cinnamic acids.

<span class="mw-page-title-main">Prodelphinidin</span>

Prodelphinidin is a name for the polymeric tannins composed of gallocatechin. It yields delphinidin during depolymerisation under oxidative conditions.

<span class="mw-page-title-main">Procyanidin C2</span> Chemical compound

Procyanidin C2 is a B type proanthocyanidin trimer, a type of condensed tannin.

A type proanthocyanidins are a specific type of proanthocyanidins, which are a class of flavonoid. Proanthocyanidins fall under a wide range of names in the nutritional and scientific vernacular, including oligomeric proanthocyanidins, flavonoids, polyphenols, condensed tannins, and OPCs. Proanthocyanidins were first popularized by French scientist Jacques Masquelier.

<span class="mw-page-title-main">Epicatechin gallate</span> Chemical compound

Epicatechin gallate (ECG) is a flavan-3-ol, a type of flavonoid, present in green tea. It is also reported in buckwheat and in grape.

<span class="mw-page-title-main">Procyanidin C1</span> Chemical compound

Procyanidin C1 (PCC1) is a B type proanthocyanidin. It is an epicatechin trimer found in grape, unripe apples, and cinnamon.

<span class="mw-page-title-main">Condensed tannin</span> Polymers formed by the condensation of flavans.

Condensed tannins are polymers formed by the condensation of flavans. They do not contain sugar residues.

<span class="mw-page-title-main">Phenolic content in tea</span> Natural plant compounds

The phenolic content in tea refers to the phenols and polyphenols, natural plant compounds which are found in tea. These chemical compounds affect the flavor and mouthfeel of tea. Polyphenols in tea include catechins, theaflavins, tannins, and flavonoids.

Catechin-7-<i>O</i>-glucoside Chemical compound

Catechin-7-O-glucoside is a flavan-3-ol glycoside formed from catechin.

<span class="mw-page-title-main">Dark chocolate</span> Chocolate with high cocoa solid content

Dark chocolate is a form of chocolate containing only cocoa solids, cocoa butter and sugar. Dark chocolate without added sweetener is known as bitter chocolate or unsweetened chocolate. As with the other two main types of chocolate, dark chocolate is used for chocolate bars or as a coating in confectionery.

<span class="mw-page-title-main">Helmut Sies</span> German biomedical research professor

Helmut Sies is a German physician, biochemist and university professor. He was the first to demonstrate the existence of hydrogen peroxide as a normal attribute of aerobic life in 1970, and he introduced the concept of Oxidative stress in 1985. He also worked on the biological strategies of antioxidant defense and the biochemistry of nutritional antioxidants.

References

  1. Ullah C, Unsicker SB, Fellenberg C, Constabel CP, Schmidt A, Gershenzon J, Hammerbacher A (December 2017). "Flavan-3-ols Are an Effective Chemical Defense against Rust Infection". Plant Physiology. 175 (4): 1560–1578. doi:10.1104/pp.17.00842. PMC   5717727 . PMID   29070515.
  2. 1 2 Schwitters B, Masquelier J (1995). OPC in Practice (3rd ed.). OCLC   45289285.
  3. Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A (May 2013). "Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases". Antioxidants & Redox Signaling. 18 (14): 1818–1892. doi:10.1089/ars.2012.4581. PMC   3619154 . PMID   22794138.
  4. Dewick PM (2009). Medicinal Natural Products: a biosynthetic approach. John Wiley & Sons. p. 168. ISBN   978-0-471-49641-0.
  5. Winkel-Shirley B (June 2001). "Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology". Plant Physiology. 126 (2): 485–493. doi:10.1104/pp.126.2.485. PMC   1540115 . PMID   11402179.
  6. Mueller-Harvey I, Feucht W, Polster J, Trnková L, Burgos P, Parker AW, Botchway SW (March 2012). "Two-photon excitation with pico-second fluorescence lifetime imaging to detect nuclear association of flavanols". Analytica Chimica Acta. 719: 68–75. doi:10.1016/j.aca.2011.12.068. PMID   22340533. S2CID   24094780.
  7. "Database on polyphenol content in foods, v. 3.6". Phenol Explorer. 2016.
  8. Hammerstone JF, Lazarus SA, Schmitz HH (August 2000). "Procyanidin content and variation in some commonly consumed foods". The Journal of Nutrition. 130 (8S Suppl): 2086S–2092S. doi: 10.1093/jn/130.8.2086S . PMID   10917927.
  9. Payne MJ, Hurst WJ, Miller KB, Rank C, Stuart DA (October 2010). "Impact of fermentation, drying, roasting, and Dutch processing on epicatechin and catechin content of cacao beans and cocoa ingredients". Journal of Agricultural and Food Chemistry. 58 (19): 10518–10527. doi:10.1021/jf102391q. PMID   20843086.
  10. Mabrym H, Harborne JB, Mabry TJ (1975). The Flavonoids. London: Chapman and Hall. ISBN   978-0-412-11960-6.
  11. Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L (May 2004). "Polyphenols: food sources and bioavailability". The American Journal of Clinical Nutrition. 79 (5): 727–747. doi: 10.1093/ajcn/79.5.727 . PMID   15113710.
  12. 1 2 Del Río D, Rodríguez Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A (May 2013). "Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases". Antioxidants & Redox Signaling. 18 (14): 1818–1892. doi:10.1089/ars.2012.4581. PMC   3619154 . PMID   22794138.
  13. Rodríguez Mateos A, Weber T, Skene SS, Ottaviani JI, Crozier A, Kelm M, et al. (December 2018). "Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial". The American Journal of Clinical Nutrition. 108 (6): 1229–1237. doi:10.1093/ajcn/nqy229. PMC   6290365 . PMID   30358831.
  14. Actis-Goretta L, Lévèques A, Rein M, Teml A, Schäfer C, Hofmann U, et al. (October 2013). "Intestinal absorption, metabolism, and excretion of (−)-epicatechin in healthy humans assessed by using an intestinal perfusion technique". The American Journal of Clinical Nutrition. 98 (4): 924–933. doi: 10.3945/ajcn.113.065789 . PMID   23864538.
  15. Kuhnle G, Spencer JP, Schroeter H, Shenoy B, Debnam ES, Srai SK, et al. (October 2000). "Epicatechin and catechin are O-methylated and glucuronidated in the small intestine". Biochemical and Biophysical Research Communications. 277 (2): 507–512. doi:10.1006/bbrc.2000.3701. PMID   11032751.
  16. Das NP (December 1971). "Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man". Biochemical Pharmacology. 20 (12): 3435–3445. doi:10.1016/0006-2952(71)90449-7. PMID   5132890.
  17. 1 2 Ottaviani JI, Borges G, Momma TY, et al. (July 2016). "The metabolome of [2-14C](−)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives". Scientific Reports. 6 (1): 29034. Bibcode:2016NatSR...629034O. doi:10.1038/srep29034. PMC   4929566 . PMID   27363516.
  18. 1 2 Ottaviani JI, Fong R, Kimball J, Ensunsa JL, Britten A, Lucarelli D, et al. (June 2018). "Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies". Scientific Reports. 8 (1): 9859. Bibcode:2018NatSR...8.9859O. doi:10.1038/s41598-018-28333-w. PMC   6026136 . PMID   29959422.
  19. Health Canada (12 December 2017). "Summary Safety Review - Green tea extract-containing natural health products - Assessing the potential risk of liver injury (hepatotoxicity)". Health Canada, Government of Canada. Retrieved 2022-05-06.
  20. Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, Filipič M, et al. (April 2018). "Scientific opinion on the safety of green tea catechins". EFSA Journal. 16 (4): e05239. doi:10.2903/j.efsa.2018.5239. PMC   7009618 . PMID   32625874.
  21. Ried K, Fakler P, Stocks NP, et al. (Cochrane Hypertension Group) (April 2017). "Effect of cocoa on blood pressure". The Cochrane Database of Systematic Reviews. 4 (5): CD008893. doi:10.1002/14651858.CD008893.pub3. PMC   6478304 . PMID   28439881.
  22. Raman G, Avendano EE, Chen S, Wang J, Matson J, Gayer B, et al. (November 2019). "Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies". The American Journal of Clinical Nutrition. 110 (5): 1067–1078. doi:10.1093/ajcn/nqz178. PMC   6821550 . PMID   31504087.
  23. "Article 13 (5): Cocoa flavanols; Search filters: Claim status - authorised; search - flavanols". European Commission, EU Register. 31 March 2015. Retrieved 8 September 2022.
  24. "Scientific Opinion on the modification of the authorisation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/20061 following a request in accordance with Article 19 of Regulation (EC) No 1924/2006". EFSA Journal. 12 (5). 2014. doi: 10.2903/j.efsa.2014.3654 .
  25. Crowe-White, Kristi M; Evans, Levi W; Kuhnle, Gunter G C; Milenkovic, Dragan; Stote, Kim; Wallace, Taylor; Handu, Deepa; Senkus, Katelyn E (3 October 2022). "Flavan-3-ols and cardiometabolic health: First ever dietary bioactive guideline". Advances in Nutrition. 13 (6): 2070–83. doi: 10.1093/advances/nmac105 . PMC   9776652 . PMID   36190328.