Flavonoid

Molecular structure of the avone backbone (2-phenyl-1,4benzopyrone)

O
Neoavonoids structure

The three avonoid classes above are all ketonecontaining compounds, and as such, are anthoxanthins
(avones and avonols). This class was the rst to
be termed bioavonoids. The terms avonoid and
bioavonoid have also been more loosely used to describe
non-ketone polyhydroxy polyphenol compounds which
are more specically termed avanoids. The three cycle or heterocycles in the avonoid backbone are generally called ring A, B and C. Ring A usually shows a
phloroglucinol substitution pattern.

Isoavan structure

Flavonoids (or bioavonoids) (from the Latin word

avus meaning yellow, their color in nature) are a class
of plant and fungus secondary metabolites.

1 Biosynthesis

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

2 Functions of avonoids in plants

avonoids or bioavonoids

Flavonoids are widely distributed in plants, fullling

isoavonoids, derived from 3-phenylchromen-4-one many functions. Flavonoids are the most important
plant pigments for ower coloration, producing yellow
(3-phenyl-1,4-benzopyrone) structure
or red/blue pigmentation in petals designed to attract
neoavonoids, derived from 4-phenylcoumarine (4- pollinator animals. In higher plants, avonoids are
phenyl-1,2-benzopyrone) structure
involved in UV ltration, symbiotic nitrogen xation
1

Flavan-3-ols use the 2-phenyl-3,4-dihydro2H-chromen-3-ol skeleton

and oral 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 avonoids 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 uxes and the formation of a root nodule. In addition, some avonoids have inhibitory activity
against organisms that cause plant diseases, e.g. Fusarium
oxysporum.[3]

Examples: Catechin (C), Gallocatechin

(GC), Catechin 3-gallate (Cg),
Gallocatechin
3-gallate
(GCg),
Epicatechins
(Epicatechin
(EC)),
Epigallocatechin (EGC), Epicatechin 3gallate (ECg), Epigallocatechin 3-gallate
(EGCg)
Theaavin
Examples:
Theaavin-3-gallate,
Theaavin-3'-gallate, Theaavin-3,3'digallate

Subgroups

Over 5000 naturally occurring avonoids have been characterized from various plants. They have been classied
according to their chemical structure, and are usually subdivided into the following subgroups (for further reading
see [4] ):
3.5

3.1

ISOFLAVONOIDS

Thearubigin
Proanthocyanidins are dimers, trimers,
oligomers, or polymers of the avanols

Anthocyanidins

Anthoxanthins

Anthoxanthins are divided into two groups:[5]

3.2

Flavanones

Flavanones

3.3

Flavanonols

Flavanonols

3.4

Flavylium skeleton of anthocyanidins

Flavans

Anthocyanidins

Anthocyanidins are the aglycones of

anthocyanins; they use the avylium (2phenylchromenylium) ion skeleton
Examples:
Cyanidin, Delphinidin,
Malvidin,
Pelargonidin,
Peonidin,
Petunidin

4 Isoavonoids
Isoavonoids
Flavan structure

Include avan-3-ols (avanols), avan-4-ols and avan3,4-diols.

Flavan-3-ols (avanols)

Isoavones use the 3-phenylchromen-4-one

skeleton (with no hydroxyl group substitution
on carbon at position 2)
Examples:
Glycitein

Genistein,

Daidzein,

5.1

Parsley

Isoavanes
Isoavandiols
Isoavenes
Coumestans
Pterocarpans

Dietary sources

A variety of avonoids are found in citrus fruits, including

grapefruit.

5.1 Parsley
Parsley is a source of avones.

Parsley, both fresh and dried, contains avones.[7]

5.2 Blueberries
Blueberries are a dietary source of anthocyanidins.[7][8]

5.3 Black tea

Black tea is a rich source of dietary avan-3-ols.[7]

5.4 Citrus

Blueberries are a source of dietary anthocyanidins.

Flavonoids (specically avanoids such as the catechins)

are the most common group of polyphenolic compounds in the human diet and are found ubiquitously
in plants.[6] Flavonols, the original bioavonoids such
as quercetin, are also found ubiquitously, but in lesser
quantities. The widespread distribution of avonoids,
their variety and their relatively low toxicity compared
to other active plant compounds (for instance alkaloids)
mean that many animals, including humans, ingest signicant quantities in their diet. Foods with a high
avonoid content include parsley,[7] onions,[7] blueberries
and other berries,[7] black tea,[7] green tea and oolong
tea,[7] bananas, all citrus fruits, Ginkgo biloba, red wine,
sea-buckthorns, and dark chocolate (with a cocoa content of 70% or greater). Further information on dietary
sources of avonoids can be obtained from the US Department of Agriculture avonoid database.[7]

The citrus avonoids include hesperidin (a glycoside

of the avanone hesperetin), quercitrin, rutin (two
glycosides of the avonol quercetin), and the avone
tangeritin.

5.5 Wine
Main article: Polyphenols in wine

5.6 Cocoa
Main article: Health eects of chocolate
Flavonoids exist naturally in cocoa, but because they
can be bitter, they are often removed from chocolate,
even dark chocolate.[9] Although avonoids are present
in milk chocolate, milk may interfere with their

7 RESEARCH

absorption;[10][11] however this conclusion has been

questioned.[12]

5.7

Peanut

Peanut (red) skin contains signicant polyphenol content,

including avonoids.[13][14]
[15]

Dietary intake

Data is based on mean avonoid intake of all countries included

in the 2011 EFSA Comprehensive European Food Consumption
Database.[16]

Drug Administration (FDA) nor the European Food

Safety Authority (EFSA) has approved any health claim
for avonoids or approved any avonoids as pharmaceutical drugs.[18][19][20] Moreover, several companies
have been cautioned by the FDA over misleading health
claims.[21][22][23][24]
Mean avonoid intake in mg/d per country, the pie charts show
the relative contribution of dierent types of avonoids. [16]

Food composition data for avonoids were provided by

the USDA database on avonoids.[7] In the United States
NHANES survey, mean avonoid intake was 190 mg/d
in adults, with avan-3-ols as the main contributor.[17] In
the European Union, based on data from EFSA, mean
avonoid intake was 140 mg/d, although there were considerable dierences between individual countries.[16]
The main type of avonoids consumed in the EU and
USA were avan-3-ols, mainly from tea, while intake of
other avonoids was considerably lower.[16][17]

Research

Though there is ongoing research into the potential health

benets of individual avonoids, neither the Food and

7.1

In vitro

Flavonoids have been shown to have a wide range

of biological and pharmacological activities in in
vitro studies.
Examples include anti-allergic,[25]
[25][26]
anti-inammatory,
antioxidant,[26]
anti[27][28]
microbial (antibacterial,
antifungal,[29][30] and
antiviral[29][30] ), anti-cancer,[26][31] and anti-diarrheal
activities.[32] Flavonoids have also been shown to inhibit
topoisomerase enzymes[33][34] and to induce DNA
mutations in the mixed-lineage leukemia (MLL) gene
in in vitro studies.[35] However, in most of the above
cases no follow up in vivo or clinical research has been
performed, leaving it impossible to say if these activities
have any benecial or detrimental eect on human
health. Biological and pharmacological activities which
have been investigated in greater depth are described
below.

7.6

7.2

Antibacterial

Antioxidant

Research at the Linus Pauling Institute and the European

Food Safety Authority shows that avonoids are poorly
absorbed in the human body (less than 5%), with most
of what is absorbed being quickly metabolized and
excreted.[20][36][37] These ndings suggest that avonoids
have negligible systemic antioxidant activity, and that the
increase in antioxidant capacity of blood seen after consumption of avonoid-rich foods is not caused directly by
avonoids, but is due to production of uric acid resulting
from avonoid depolymerization and excretion.[38]

5
inhibit coagulation, thrombus formation or platelet
aggregation
reduce risk of atherosclerosis
reduce arterial blood pressure and risk of
hypertension
reduce oxidative stress and related signaling pathways in blood vessel cells
modify vascular inammatory mechanisms
improve endothelial and capillary function
modify blood lipid levels

7.3

Inammation

regulate carbohydrate and glucose metabolism

Inammation has been implicated as a possible ori modify mechanisms of aging

gin of numerous local and systemic diseases, such as
cancer,[39] cardiovascular disorders,[40] diabetes melli- Listed on the clinical trial registry of the US National Intus,[41] and celiac disease.[42]
stitutes of Health (July 2016) are 48 human studies comPreliminary studies indicate that avonoids may aect pleted or underway to study the dietary eects of plant
anti-inammatory mechanisms via their ability to inhibit avonoids on cardiovascular diseases.[55]
reactive oxygen or nitrogen compounds.[43] Flavonoids However, population-based studies have failed to show
have also been proposed to inhibit the pro-inammatory a strong benecial eect [56] which might be due to the
activity of enzymes involved in free radical production, considerably lower intake in the habitual diet of those insuch as cyclooxygenase, lipoxygenase or inducible ni- vestigated.
tric oxide synthase,[43][44] and to modify intracellular
signaling pathways in immune cells,[43] or in brain cells
after a stroke.[45]
7.6 Antibacterial
Procyanidins, a class of avonoids, have been shown in
preliminary research to have anti-inammatory mechanisms including modulation of the arachidonic acid pathway, inhibition of gene transcription, expression and activity of inammatory enzymes, as well as secretion of
anti-inammatory mediators.[46]

7.4

Cancer

Clinical studies investigating the relationship between avonoid consumption and cancer prevention/development are conicting for most types of
cancer, probably because most studies are retrospective
in design and use a small sample size.[47] Two apparent
exceptions are gastric carcinoma and smoking-related
cancers. Dietary avonoid intake is associated with reduced gastric carcinoma risk in women,[48] and reduced
aerodigestive tract cancer risk in smokers.[49]

7.5

Cardiovascular diseases

Flavonoids have been shown to have (a) direct

antibacterial activity, (b) synergistic activity with
antibiotics, and (c) the ability to suppress bacterial
virulence factors in numerous in vitro and a limited
number of in vivo studies.[27][57] Noteworthy among the
in vivo studies[58][59][60] is the nding that oral quercetin
protects guinea pigs against the Group 1 carcinogen
Helicobacter pylori.[60] Researchers from the European
Prospective Investigation into Cancer and Nutrition have
speculated this may be one reason why dietary avonoid
intake is associated with reduced gastric carcinoma risk
in European women.[61] Additional in vivo and clinical
research is needed to determine if avonoids could
be used as pharmaceutical drugs for the treatment of
bacterial infection, or whether dietary avonoid intake
oers any protection against infection.

8 Synthesis, detection, quantication, and semi-synthetic alterations

Among the most intensively studied of general human

disorders possibly aected by dietary avonoids, prelimi- 8.1 Color Spectrum
nary cardiovascular disease research has revealed the following mechanisms under investigation in patients or nor- Flavonoid synthesis in plants is induced by light color
spectrums at both high and low energy radiations. Low
mal subjects:[50][51][52][53][54]

10

energy radiations are accepted by phytochrome, while

high energy radiations are accepted by carotenoids,
avins, cryptochromes in addition to phytochromes.
The photomorphogenic process of phytochome-mediated
avonoid biosynthesis has been observed in Amaranthus,
barley, maize, Sorgham and turnip. Red light promotes
avonoid synthesis.[62]

REFERENCES

9 See also
Phytochemical
List of antioxidants in food
List of phytochemicals in food
Phytochemistry

8.2

Availability through microorganisms

Several recent research articles have demonstrated the efcient production of avonoid molecules from genetically
engineered microorganisms.[63][64][65]

8.3

Tests for detection

Shinoda test
Four pieces of magnesium llings are added to the
ethanolic extract followed by few drops of concentrated hydrochloric acid. A pink or red colour indicates
the presence of avonoid.[66] Colours varying from orange to red indicated avones, red to crimson indicated
avonoids, crimson to magenta indicated avonones.
Sodium hydroxide test
About 5 mg of the compound is dissolved in water,
warmed and ltered. 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 avonoids.[67]
p-Dimethylaminocinnamaldehyde test
A colorimetric assay based upon the reaction of A-rings
with the chromogen p-dimethylaminocinnamaldehyde
(DMACA) has been developed for avanoids in beer that
can be compared with the vanillin procedure.[68]

8.4

Quantication

Lamaison and Carnet have designed a test for the determination of the total avonoid 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.[69]

8.5

Semi-synthetic alterations

Immobilized Candida antarctica lipase can be used to

catalyze the regioselective acylation of avonoids.[70]

Secondary metabolites
Homoisoavonoids, related chemicals with a 16 carbons skeleton

10 References
[1] McNaught, Alan D; Wilkinson, Andrew; IUPAC
(1997), IUPAC Compendium of Chemical Terminology, IUPAC Compendium of Chemical Terminology (2 ed.), Oxford:
Blackwell Scientic,
doi:10.1351/goldbook.F02424, ISBN 0-9678550-9-8
[2] The Gold Book. 2009. doi:10.1351/goldbook. ISBN
0-9678550-9-8. Retrieved 16 September 2012. |chapter=
ignored (help)
[3] Galeotti, F; Barile, E; Curir, P; Dolci, M; Lanzotti, V
(2008). Flavonoids from carnation (Dianthus caryophyllus) and their antifungal activity. Phytochemistry Letters.
1: 4448. doi:10.1016/j.phytol.2007.10.001.
[4] Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (October 2007). Biotechnology of avonoids and other phenylpropanoid-derived
natural products. Part I: Chemical diversity, impacts on
plant biology and human health. Biotechnology Journal.
2 (10): 121434. doi:10.1002/biot.200700084. PMID
17935117.
[5] Isolation of a UDP-glucose:
Flavonoid 5-Oglucosyltransferase gene and expression analysis of
anthocyanin biosynthetic genes in herbaceous peony
(Paeonia lactiora 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
[6] Spencer JP (2008). Flavonoids: modulators of brain
function?". British Journal of Nutrition. 99: ES6077.
doi:10.1017/S0007114508965776. PMID 18503736.
[7] USDAs Database on the Flavonoid Content
[8] Ayoub M, de Camargo AC, Shahidi F (2016).
Antioxidants and bioactivities of free, esteried
and insoluble-bound phenolics from berry seed
meals. Food Chemistry. 197 (Part A): 221232.
doi:10.1016/j.foodchem.2015.10.107.
[9] The devil in the dark chocolate. Lancet. 370 (9605):
2070. 2007. doi:10.1016/S0140-6736(07)61873-X.
PMID 18156011.

[10] Serani M, Bugianesi R, Maiani G, Valtuena S, De

Santis S, Crozier A (2003). Plasma antioxidants
from chocolate.
Nature.
424 (6952): 1013.
Bibcode:2003Natur.424.1013S. doi:10.1038/4241013a.
PMID 12944955.

[22] Inspections, Compliance, Enforcement, and Criminal Investigations (Unilever, Inc.)". US Food and Drug Administration. Retrieved 25 October 2013.
[23] Lipton green tea is a drug. NutraIngredients-USA.com.
Retrieved 25 October 2013.

[11] Serani M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A (2003). Nutrition: milk and absorption of dietary avanols. Nature. 424 (6952): 1013.
Bibcode:2003Natur.424.1013S. doi:10.1038/4241013a.
PMID 12944955.

[24] Fruits Are Good for Your Health? Not So Fast: FDA
Stops Companies From Making Health Claims About
Foods. TheDailyGreen.com. Retrieved 25 October
2013.

[12] Roura E, et al. (2007). Milk Does Not Aect the

Bioavailability of Cocoa Powder Flavonoid in Healthy
51: 493498.
Human (PDF). Ann Nutr Metab.
doi:10.1159/000111473.

[25] Yamamoto Y, Gaynor RB (2001). Therapeutic potential of inhibition of the NF-B pathway in the treatment
of inammation and cancer. Journal of Clinical Investigation. 107 (2): 13542. doi:10.1172/JCI11914. PMC
199180 . PMID 11160126.

[13] de Camargo AC, Regitano-d'Arce MA, Gallo CR, Shahidi

F (2015). Gamma-irradiation induced changes in microbiological status, phenolic prole and antioxidant activity
of peanut skin. Journal of Functional Foods. 12: 129
143. doi:10.1016/j.j.2014.10.034.
[14] 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): 494152. doi:10.3390/ijms10114941. PMID
20087468.
[15] Flavonoids - Linus Pauling Institute - Oregon State University. Retrieved 26 February 2016.
[16] 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.
[17] Chun, O. K.; Chung, S. J.; Song, W. O. (2007). Estimated dietary avonoid intake and major food sources of
U.S. Adults. The Journal of Nutrition. 137 (5): 1244
52. PMID 17449588.
[18] FDA approved drug products. US Food and Drug Administration. Retrieved 8 November 2013.
[19] Health Claims Meeting Signicant Scientic Agreement. US Food and Drug Administration. Retrieved 8
November 2013.
[20] EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3 European Food Safety Authority (EFSA),
Parma, Italy (2010). Scientic 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 (PDF). EFSA Journal. 8 (2):
1489. doi:10.2903/j.efsa.2010.1489.
[21] Inspections, Compliance, Enforcement, and Criminal Investigations (Flavonoid Sciences)". US Food and Drug
Administration. Retrieved 8 November 2013.

[26] Cazarolli LH, Zanatta L, Alberton EH, Figueiredo MS,

Folador P, Damazio RG, Pizzolatti MG, Silva FR (2008).
Flavonoids: Prospective Drug Candidates. MiniReviews in Medicinal Chemistry. 8 (13): 14291440.
doi:10.2174/138955708786369564. PMID 18991758.
[27] Cushnie TP, Lamb AJ (2011). Recent advances in understanding the antibacterial properties of avonoids.
International Journal of Antimicrobial Agents. 38 (2):
99107. doi:10.1016/j.ijantimicag.2011.02.014. PMID
21514796.
[28] Manner S, Skogman M, Goeres D, Vuorela P, Fallarero A
(2013). Systematic exploration of natural and synthetic
avonoids for the inhibition of Staphylococcus aureus
biolms. International Journal of Molecular Sciences. 14
(10): 1943419451. doi:10.3390/ijms141019434. PMC
3821565 . PMID 24071942.
[29] Cushnie TP, Lamb AJ (2005).
Antimicrobial
activity of avonoids (PDF). International Journal of Antimicrobial Agents.
26 (5): 343356.
doi:10.1016/j.ijantimicag.2005.09.002.
PMID
16323269.
[30] Friedman M (2007). Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea avonoids
and teas. Molecular Nutrition and Food Research. 51
(1): 116134. doi:10.1002/mnfr.200600173. PMID
17195249.
[31] de Sousa RR, Queiroz KC, Souza AC, Gurgueira SA,
Augusto AC, Miranda MA, Peppelenbosch MP, Ferreira CV, Aoyama H (2007). Phosphoprotein levels,
MAPK activities and NFkappaB expression are aected
by setin. J Enzyme Inhib Med Chem. 22 (4): 439444.
doi:10.1080/14756360601162063. PMID 17847710.
[32] Schuier M, Sies H, Illek B, Fischer H (2005). Cocoarelated avonoids inhibit CFTR-mediated chloride transport across T84 human colon epithelia. J. Nutr. 135 (10):
23205. PMID 16177189.
[33] Esselen M, Fritz J, Hutter M, Marko D (2009). Delphinidin Modulates the DNA-Damaging Properties of
Topoisomerase II Poisons. Chemical Research in Toxicology. 22 (3): 55464. doi:10.1021/tx800293v. PMID
19182879.

[34] Bandele OJ, Clawson SJ, Oshero N (2008). Dietary

polyphenols as topoisomerase II poisons: B-ring substituents determine the mechanism of enzyme-mediated
DNA cleavage enhancement. Chemical Research in Toxicology. 21 (6): 12531260. doi:10.1021/tx8000785.
PMC 2737509 . PMID 18461976.
[35] Barjesteh van Waalwijk van Doorn-Khosrovani S, Janssen
J, Maas LM, Godschalk RW, Nijhuis JG, van Schooten FJ
(2007). Dietary avonoids induce MLL translocations in
primary human CD34+ cells. Carcinogenesis. 28 (8):
17039. doi:10.1093/carcin/bgm102. PMID 17468513.
[36] Lotito SB, Frei B (2006). Consumption of avonoidrich foods and increased plasma antioxidant capacity in
humans: cause, consequence, or epiphenomenon?".
Free Radic.
Biol.
Med.
41 (12): 172746.
doi:10.1016/j.freeradbiomed.2006.04.033.
PMID
17157175.
[37] Williams RJ, Spencer JP, Rice-Evans C (2004).
Flavonoids: antioxidants or signalling molecules?".
Free Radical Biology & Medicine. 36 (7): 83849.
doi:10.1016/j.freeradbiomed.2004.01.001.
PMID
15019969.
[38] Stauth D (5 March 2007). Studies force new view on
biology of avonoids. EurekAlert!, Adapted from a news
release issued by Oregon State University.
[39] 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): 28212831.
doi:10.1016/j.biocel.2013.10.004. PMID 24128857.
[40] Manach C, Mazur A, Scalbert A (2005). Polyphenols
and prevention of cardiovascular diseases. Current opinion in lipidology. 16 (1): 7784. doi:10.1097/00041433200502000-00013. PMID 15650567.
[41] Babu PV, Liu D, Gilbert ER (2013). Recent advances
in understanding the anti-diabetic actions of dietary
avonoids. The Journal of Nutritional Biochemistry. 24
(11): 17771789. doi:10.1016/j.jnutbio.2013.06.003.
PMC 3821977 . PMID 24029069.
[42] Ferretti G, Bacchetti T, Masciangelo S, Saturni L (2012).
Celiac Disease, Inammation and Oxidative Damage:
A Nutrigenetic Approach. Nutrients. 4 (12): 243
257. doi:10.3390/nu4040243. PMC 3347005 . PMID
22606367.
[43] Izzi V, Masuelli L, Tresoldi I, Sacchetti P, Modesti
A, Galvano F, Bei R (2012). The eects of dietary
avonoids on the regulation of redox inammatory networks. Frontiers in bioscience (Landmark edition). 17
(7): 23962418. doi:10.2741/4061. PMID 22652788.
[44] Gomes A, Couto D, Alves A, Dias I, Freitas M, Porto
G, Duarte JA, Fernandes E (2012). Trihydroxyavones
with antioxidant and anti-inammatory ecacy. BioFactors. 38 (5): 378386. doi:10.1002/biof.1033. PMID
22806885.

10

REFERENCES

[45] Chang CF, Cho S, Wang J (Apr 2014). "(-)-Epicatechin

protects hemorrhagic brain via synergistic Nrf2 pathways.
Ann Clin Transl Neurol.
1 (4): 258
271. doi:10.1002/acn3.54. PMC 3984761 . PMID
24741667.
[46] Martinez-Micaelo N, Gonzlez-Abun N, Ardvol A,
Pinent M, Blay MT (2012). Procyanidins and inammation: Molecular targets and health implications. BioFactors. 38 (4): 257265. doi:10.1002/biof.1019. PMID
22505223.
[47] Romagnolo DF, Selmin OI (2012).
Flavonoids
and cancer prevention:
a review of the evidence. J Nutr Gerontol Geriatr. 31 (3): 20638.
doi:10.1080/21551197.2012.702534. PMID 22888839.
[48] Gonzlez CA, Sala N, Rokkas T (2013). Gastric cancer:
epidemiologic aspects. Helicobacter. 18 (Supplement 1):
3438. doi:10.1111/hel.12082. PMID 24011243.
[49] Woo HD, Kim J (2013). Dietary avonoid intake and
smoking-related cancer risk: a meta-analysis. PLoS
ONE. 8 (9): e75604. Bibcode:2013PLoSO...875604W.
doi:10.1371/journal.pone.0075604. PMC 3777962 .
PMID 24069431.
[50] Higdon, J; Drake, V; Frei, B (March 2009). NonAntioxidant Roles for Dietary Flavonoids: Reviewing
the relevance to cancer and cardiovascular diseases.
Nutraceuticals World. Rodman Media. Retrieved 24
November 2013.
[51] van Dam RM, Naidoo N, Landberg R (2013). Dietary
avonoids and the development of type 2 diabetes and
cardiovascular diseases. Current Opinion in Lipidology.
24 (1): 2533. doi:10.1097/MOL.0b013e32835bcd.
PMID 23254472.
[52] Tangney CC, Rasmussen HE (2013). Polyphenols,
Inammation,
and
Cardiovascular
Disease.
Current Atherosclerosis Reports.
15 (5):
324.
doi:10.1007/s11883-013-0324-x.
PMC 3651847 .
PMID 23512608.
[53] Siasos G, Tousoulis D, Tsigkou V, Kokkou E, Oikonomou
E, Vavuranakis M, Basdra EK, Papavassiliou AG,
Stefanadis C (2013).
Flavonoids in atherosclerosis: An overview of their mechanisms of action.
Current medicinal chemistry. 20 (21): 26412660.
doi:10.2174/0929867311320210003. PMID 23627935.
[54] Cappello, AR, Dolce V, Iacopetta D, Martello M,
Fiorillo M, Curcio R, Muto L, Dhanyalayam D.
(2015). Bergamot (Citrus bergamia Risso) Flavonoids
and Their Potential Benets in Human Hyperlipidemia and Atherosclerosis: an Overview.
MiniReviews in Medicinal Chemistry.
15 (8): 111.
doi:10.2174/1389557515666150709110222.
PMID
26156545.
[55] Search Results. Flavonoids in cardiovascular disease
clinical trials. Clinicaltrials.gov. US National Institutes
of Health. Retrieved November 24, 2013.

[56] 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): 111.
doi:10.1017/S000711451300278X. PMID 23953879.
[57] Taylor PW, Hamilton-Miller JM, Stapleton PD (2005).
Antimicrobial properties of green tea catechins. Food
Science and Technology Bulletin.
2 (7): 7181.
doi:10.1616/1476-2137.14184. PMC 2763290 . PMID
19844590.
[58] Choi O, Yahiro K, Morinaga N, Miyazaki M, Noda
M (2007).
Inhibitory eects of various plant
polyphenols on the toxicity of Staphylococcal alphatoxin. Microbial Pathogenesis. 432 (56): 215224.
doi:10.1016/j.micpath.2007.01.007. PMID 17391908.
[59] Oh DR, Kim JR, Kim YR (2010). Genistein inhibits
Vibrio vulnicus adhesion and cytotoxicity to HeLa cells.
Archives of Pharmacal Research. 33 (5): 787792.
doi:10.1007/s12272-010-0520-y. PMID 20512479.
[60] Gonzlez-Segovia R, Quintanar JL, Salinas E, CeballosSalazar R, Aviles-Jimnez F, Torres-Lpez J (2008). Effect of the avonoid quercetin on inammation and lipid
peroxidation induced by Helicobacter pylori in gastric
mucosa of guinea pig. Journal of Gastroenterology. 43
(6): 441447. doi:10.1007/s00535-008-2184-7. PMID
18600388.
[61] Zamora-Ros R, Agudo A, Lujn-Barroso L, Romieu I,
Ferrari P, Knaze V, Bueno-de-Mesquita HB, Leenders M,
Travis RC, Navarro C, Snchez-Cantalejo E, Slimani N,
Scalbert A, Fedirko V, Hjartker A, Engeset D, Skeie G,
Boeing H, Frster J, Li K, Teucher B, Agnoli C, Tumino
R, Mattiello A, Saieva C, Johansson I, Stenling R, Redondo ML, Wallstrm P, Ericson U, Khaw KT, Mulligan
AA, Trichopoulou A, Dilis V, Katsoulis M, Peeters PH,
Igali L, Tjnneland A, Halkjr J, Touillaud M, Perquier
F, Fagherazzi G, Amiano P, Ardanaz E, Bredsdor L,
Overvad K, Ricceri F, Riboli E, Gonzlez CA (2012).
Dietary avonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. American Journal of Clinical Nutrition. 96 (6): 13981408.
doi:10.3945/ajcn.112.037358. PMID 23076618.
[62] Sinha, Rajiv Kumar (2004-01-01). Modern Plant Physiology. CRC Press. p. 457. ISBN 9780849317149.
[63] Hwang EI, Kaneko M, Ohnishi Y, Horinouchi S
(May 2003). Production of plant-specic avanones
by Escherichia coli containing an articial gene cluster. Appl. Environ. Microbiol. 69 (5): 2699
706. doi:10.1128/AEM.69.5.2699-2706.2003. PMC
154558 . PMID 12732539.
[64] Trantas E, Panopoulos N, Ververidis F (2009).
Metabolic engineering of the complete pathway
leading to heterologous biosynthesis of various
avonoids and stilbenoids in Saccharomyces cerevisiae". Metabolic Engineering. 11 (6): 355366.
doi:10.1016/j.ymben.2009.07.004. PMID 19631278.

[65] Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (2007). Biotechnology

of avonoids and other phenylpropanoid-derived natural
products. Part II: Reconstruction of multienzyme pathways in plants and microbes. Biotechnology Journal.
2 (10): 123549. doi:10.1002/biot.200700184. PMID
17935118.
[66] Yisa, Jonathan (2009). Phytochemical Analysis and Antimicrobial Activity Of Scoparia Dulcis and Nymphaea
Lotus. Australian Journal of Basic and Applied Sciences.
3 (4): 39753979.
[67] Bello IA, Ndukwe GI, Audu OT, Habila JD (2011). A
bioactive avonoid from Pavetta crassipes K. Schum.
Organic and Medicinal Chemistry Letters. 1 (1): 14.
doi:10.1186/2191-2858-1-14. PMC 3305906 . PMID
22373191.
[68] A new colourimetric assay for avonoids in pilsner beers.
Jan A. Delcour and Didier Janssens de Varebeke, Journal of the Institute of Brewing, JanuaryFebruary 1985,
Volume 91, Issue 1, pages 3740, doi:10.1002/j.20500416.1985.tb04303.x
[69] Lamaison, JL; Carnet, A (1991). Teneurs en principaux
avonoides des eurs de Cratageus monogyna Jacq et de
Cratageus Laevigata (Poiret D.C) en Fonction de la vegetation. Plantes Medicinales Phytotherapie. 25: 1216.
[70] Passicos E, Santarelli X, Coulon D (2004). Regioselective acylation of avonoids catalyzed by
immobilized Candida antarctica lipase under reduced
pressure. Biotechnol Lett. 26 (13): 10731076.
doi:10.1023/B:BILE.0000032967.23282.15.
PMID
15218382.

11 Further reading
Andersen, .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)
The systematic identication of avonoids, by T.J.
Mabry, K.R. Markham and M.B. Thomas, 1970,
doi:10.1016/0022-2860(71)87109-0

12 External links
Micronutrient Information Center Flavonoids, Linus Pauling Institute, Oregon State University, Corvallis, 2015

10

12.1

12

Databases

USDA Database for the Flavonoid Content of Selected Foods, Release 3.1 (December 2013); data
for 506 foods in the 5 subclasses of avonoids provided in a separate PDF updated May 2014

EXTERNAL LINKS

11

13
13.1

Text and image sources, contributors, and licenses

Text

Flavonoid Source: https://en.wikipedia.org/wiki/Flavonoid?oldid=760212835 Contributors: Bryan Derksen, Menchi, Ronz, Djnjwd, Dysprosia, Maximus Rex, ThereIsNoSteve, Oyo, Ojigiri~enwiki, Auric, Enz1, Techelf, Wolfkeeper, Everyking, Emrys2, St3vo, Mboverload, Espetkov, CryptoDerk, Onco p53, Louison, Chiu frederick, Bradlegar, Joyous!, Spectatrix, R, Rich Farmbrough, Cfailde, Xezbeth,
Bender235, Brian0918, El C, Dennis Brown, Bobo192, Arcadian, Kjkolb, Goncalo.justino, MPerel, Pearle, MatthewEHarbowy, AnnaP,
Keenan Pepper, Echuck215, Velella, ClockworkSoul, Evil Monkey, Ceyockey, Alvis, Woohookitty, Fingers-of-Pyrex, LoopZilla, Robert
K S, Queerudite, Pacobob, Ajshm, Pfalstad, DePiep, Rjwilmsi, Ctdunstan, FlaBot, Ian Pitchford, Ground Zero, Margosbot~enwiki, Jrtayloriv, Nastajus, WriterHound, YurikBot, Wavelength, Michaeladenner, Crotalus horridus, RussBot, Reo On, Sarranduin, Chuck Carroll,
Stephenb, EdgarEdwinCayce, Gaius Cornelius, Shaddack, Bota47, TheOne, Modify, SV Resolution, Spliy, Buybooks Marius, Sller,
N3362, Itub, SmackBot, Thelukeeect, Slashme, Kakistocrat, Unyoyega, EncycloPetey, Eskimbot, Mtrantas, Edgar181, Cazort, Daeve,
Andy M. Wang, Tyciol, Rickman1969, SlimJim, RDBrown, Jprg1966, Emufarmers, Smt w, Corecirculator, Deli nk, Uthbrian, Sbharris,
Tsca.bot, Redwraith94, PrometheusX303, alyosha, Drphilharmonic, Jngers88, Bezapt, GiollaUidir, AThing, Anlace, Cody5, John,
Moop stick, Waggers, Peyre, Sasata, Iridescent, LAlawMedMBA, Acquisative, Noodlez84, Johner, MrFish, Kupirijo, Indeterminate,
Agne27, Christian75, Thijs!bot, Heroeswithmetaphors, Katnap01, Transhumanist, TimVickers, Dougher, JAnDbot, Arch dude, Greensburger, VoABot II, Vassiln, Je Dahl, LanJack, DerHexer, Nevit, Rickterp, HappyM, Nono64, J.delanoy, Boghog, Lhynard, Rod57,
Juliancolton, Idioma-bot, VolkovBot, TXiKiBoT, Myrmeleon formicarius~enwiki, Una Smith, Noformation, TML, Doc James, Logan,
Wikiapg, TheAngriestPharmacist, Alexbrn, Cablehorn, Winetype, Vanished User 8902317830, ImperfectlyInformed, Yikrazuul, Desoto10, Doseiai2, Sensonet, Ktr101, Rook2pawn, Silasmellor, Thingg, DumZiBoT, Nathan Johnson, Alternaid, Pvalue01, Addbot, DOI
bot, Jamieninjasun, EGGArgost, JamesMMc, Shakiestone, Lightbot, BeardWand, Luckas-bot, Vedran12, Yobot, Orac29, AnomieBOT,
Microbiologist 2, Walrus heart, Piano non troppo, Carolina wren, Godofthemachines, Crecy99, Materialscientist, Citation bot, ArthurBot, Xqbot, Capricorn42, Grosplant, J, Sirbidzia, Almabot, Omnipaedista, Zefr, RibotBOT, CeliaRSC, FrescoBot, Happiness4ever,
Citation bot 1, JIK1975, Moonraker, Trappist the monk, Chaamjamal, Amkilpatrick, Masondickson, RjwilmsiBot, Motown789, Androstachys, EmausBot, John of Reading, Dcirovic, Mraries, Aur, 24Adrianus, Turboscience, AManWithNoPlan, Erianna, Brandmeister,
Pbecker56, ChuispastonBot, Kuba scher, Ds2207, Luigi90, Skoot13, Helpful Pixie Bot, Bibcode Bot, BG19bot, 4551192617Alley, Paul
Kemp~enwiki, MissyMaddie, AwamerT, NotWith, Granateple, Markwdck, Shisha-Tom, Imerologul, ChrisGualtieri, SaaKasal, Mrbigtoe,
Project Osprey, Sbalfour, Landsbergit, Crvganesh, Evolution and evolvability, Shearyer, Thgj, Stomperinky, Lialono, Bashot21, Monkbot,
Alan Merrit, Amre57, KasparBot, Plantlady223, Ggux, Zupotachyon and Anonymous: 209

13.2

Images

File:2-Phenyl-1,4-benzopyrone.svg Source: https://upload.wikimedia.org/wikipedia/commons/c/c6/Flavon.svg License: Public domain

Contributors: Own work Original artist: NEUROtiker
File:4-phenylcoumarin.PNG Source: https://upload.wikimedia.org/wikipedia/commons/3/32/4-phenylcoumarin.PNG License: Public
domain Contributors: Own work Original artist: Nono64
File:Flavan-3,4-diol.svg Source:
https://upload.wikimedia.org/wikipedia/commons/b/b7/Flavan-3%2C4-diol.svg License:
CC
BY-SA 3.0 Contributors: This le was derived from Leucoanthocyanidin.PNG: <a href='//commons.wikimedia.org/wiki/File:
Leucoanthocyanidin.PNG'
class='image'><img
alt='Leucoanthocyanidin.PNG'
src='https://upload.wikimedia.org/wikipedia/
commons/thumb/2/2b/Leucoanthocyanidin.PNG/50px-Leucoanthocyanidin.PNG'
width='50'
height='39'
srcset='https:
//upload.wikimedia.org/wikipedia/commons/thumb/2/2b/Leucoanthocyanidin.PNG/75px-Leucoanthocyanidin.PNG
1.5x,
https://upload.wikimedia.org/wikipedia/commons/thumb/2/2b/Leucoanthocyanidin.PNG/100px-Leucoanthocyanidin.PNG
2x'
data-le-width='373' data-le-height='289' /></a>
Original artist: Leucoanthocyanidin.PNG: Nono64
File:Flavan-3-ol.svg Source: https://upload.wikimedia.org/wikipedia/commons/6/6e/Flavan-3-ol.svg License: Public domain Contributors: Own work Original artist: Ed (Edgar181)
File:Flavan-4-ol.svg Source: https://upload.wikimedia.org/wikipedia/commons/1/1d/Flavan-4-ol.svg License: CC BY-SA 3.0 Contributors: This le was derived from Flavan-4-ol.PNG: <a href='//commons.wikimedia.org/wiki/File:Flavan-4-ol.PNG' class='image'><img
alt='Flavan-4-ol.PNG'
src='https://upload.wikimedia.org/wikipedia/commons/thumb/2/22/Flavan-4-ol.PNG/50px-Flavan-4-ol.PNG'
width='50' height='38' srcset='https://upload.wikimedia.org/wikipedia/commons/thumb/2/22/Flavan-4-ol.PNG/75px-Flavan-4-ol.PNG
1.5x, https://upload.wikimedia.org/wikipedia/commons/thumb/2/22/Flavan-4-ol.PNG/100px-Flavan-4-ol.PNG 2x' data-le-width='367'
data-le-height='282' /></a>
Original artist: Flavan-4-ol.PNG: Nono64
File:Flavan_acsv.svg Source: https://upload.wikimedia.org/wikipedia/commons/3/3e/Flavan_acsv.svg License: Public domain Contributors: Selfmade with ChemDraw. Original artist: Calvero.
File:Flavanone_skeleton_colored.svg Source: https://upload.wikimedia.org/wikipedia/commons/b/bd/Flavanone_skeleton_colored.svg
License: CC BY-SA 3.0 Contributors: Transferred from en.wikipedia to Commons by Micha Sobkowski using CommonsHelper. Original
artist: Kupirijo at English Wikipedia
File:Flavanonol_skeleton_colored.svg Source: https://upload.wikimedia.org/wikipedia/commons/8/88/Flavanonol_skeleton_colored.
svg License: CC BY-SA 3.0 Contributors: Transferred from en.wikipedia to Commons by Micha Sobkowski using CommonsHelper.
Original artist: Kupirijo at English Wikipedia
File:Flavone_skeleton_colored.svg Source: https://upload.wikimedia.org/wikipedia/commons/3/3c/Flavone_skeleton_colored.svg License: CC BY-SA 3.0 Contributors: Transferred from en.wikipedia to Commons by Micha Sobkowski using CommonsHelper. Original
artist: Kupirijo at English Wikipedia
File:Flavonoid_intake_of_adults_(18_to_64_years)_in_the_European_Union.png Source: https://upload.wikimedia.org/wikipedia/
commons/2/27/Flavonoid_intake_of_adults_%2818_to_64_years%29_in_the_European_Union.png License: CC BY 4.0 Contributors:
Vogiatzoglou A, Mulligan AA, Lentjes MAH, Luben RN, Spencer JPE, Schroeter H, et al. (2015) Flavonoid Intake in European Adults (18

12

13

TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES

to 64 Years). PLoS ONE 10(5): e0128132. doi:10.1371/journal.pone.0128132 Original artist: Anna Vogiatzoglou, Angela A. Mulligan,
Marleen A. H. Lentjes, Robert N. Luben, Jeremy P. E. Spencer, Hagen Schroeter, Kay-Tee Khaw, Gunter G. C. Kuhnle
File:Flavonol_skeleton_colored.svg Source: https://upload.wikimedia.org/wikipedia/commons/0/0e/Flavonol_skeleton_colored.svg License: CC BY-SA 3.0 Contributors: Transferred from en.wikipedia to Commons by Micha Sobkowski using CommonsHelper. Original
artist: Kupirijo at English Wikipedia
File:Flavylium_cation.svg Source: https://upload.wikimedia.org/wikipedia/commons/f/ff/Flavylium_cation.svg License: Public domain
Contributors: Own work Original artist: Yikrazuul
File:Grapefruit_Schnitt_2008-3-3.JPG
Source:
https://upload.wikimedia.org/wikipedia/commons/d/d8/Grapefruit_Schnitt_
2008-3-3.JPG License: CC BY-SA 3.0 Contributors: Own work Original artist: Hedwig Storch
File:Isoflavan.svg Source: https://upload.wikimedia.org/wikipedia/commons/3/3a/Isoflavan.svg License: Public domain Contributors:
Own work Original artist: Ed (Edgar181)
File:Lock-green.svg Source: https://upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg License: CC0 Contributors: en:File:
Free-to-read_lock_75.svg Original artist: User:Trappist the monk
File:Main_types_and_sources_of_flavonoids_consumed_by_adults_(18_to_64_years)_in_the_European_Union.png
Source:
https://upload.wikimedia.org/wikipedia/commons/9/99/Main_types_and_sources_of_flavonoids_consumed_by_adults_%2818_to_
64_years%29_in_the_European_Union.png License: CC BY 4.0 Contributors: Vogiatzoglou A, Mulligan AA, Lentjes MAH, Luben
RN, Spencer JPE, Schroeter H, et al. (2015) Flavonoid Intake in European Adults (18 to 64 Years). PLoS ONE 10(5): e0128132.
doi:10.1371/journal.pone.0128132 Original artist: Anna Vogiatzoglou, Angela A. Mulligan, Marleen A. H. Lentjes, Robert N. Luben,
Jeremy P. E. Spencer, Hagen Schroeter, Kay-Tee Khaw, Gunter G. C. Kuhnle
File:Parsley100.jpg Source: https://upload.wikimedia.org/wikipedia/commons/b/bf/Parsley100.jpg License: CC BY-SA 3.0 Contributors: Own work Original artist: Tharish
File:PattsBlueberries.jpg Source: https://upload.wikimedia.org/wikipedia/commons/8/88/PattsBlueberries.jpg License: Public domain
Contributors: Transferred from en.wikipedia to Commons. Original artist: PhreddieH3 at English Wikipedia

13.3

Content license

Creative Commons Attribution-Share Alike 3.0