Editing Flavonoid

{{Redirect|Vitamin P|other uses|Vitamin P (disambiguation)}}

{{short description|Class of plant and fungus secondary metabolites}}
[[File:Flavon.svg|thumb|upright|Molecular structure of the [[flavone]] backbone (2-phenyl-1,4-benzopyrone)]]
[[File:Isoflavan.svg|thumb|upright|Isoflavan structure]]
[[File:4-phenylcoumarin.svg|thumb|upright|Neoflavonoids structure]]
'''Flavonoids''' (or '''bioflavonoids'''; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of [[polyphenol]]ic [[secondary metabolite]]s found in plants, and thus commonly consumed in the diets of humans.<ref name=lpi-flav/>

Chemically, flavonoids have the general structure of a 15-carbon skeleton, which consists of two [[phenyl]] rings (A and B) and a [[Heterocyclic compound|heterocyclic ring]] (C, the ring containing the embedded [[oxygen]]).<ref name="lpi-flav">{{cite web | vauthors = Delage B | title = Flavonoids | url=http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids|publisher=[[Linus Pauling Institute]], [[Oregon State University]], [[Corvallis, Oregon]]|access-date=January 26, 2021|date=November 2015}}</ref><ref name = "de_Souza_2021">{{cite journal | vauthors = de Souza Farias SA, da Costa KS, Martins JB | title = Analysis of Conformational, Structural, Magnetic, and Electronic Properties Related to Antioxidant Activity: Revisiting Flavan, Anthocyanidin, Flavanone, Flavonol, Isoflavone, Flavone, and Flavan-3-ol | journal = ACS Omega | volume = 6 | issue = 13 | pages = 8908–8918 | date = April 2021 | pmid = 33842761 | pmc = 8028018 | doi = 10.1021/acsomega.0c06156 }}</ref> This carbon structure can be abbreviated C6-C3-C6. According to the [[IUPAC]] nomenclature,<ref name="iupac">{{Citation |title=IUPAC Compendium of Chemical Terminology |edition=2nd | vauthors = McNaught AD, Wilkinson A |publisher=Blackwell Scientific |place=Oxford |year=1997 |doi=10.1351/goldbook.F02424 |isbn = 978-0-9678550-9-7|doi-access=free }}</ref><ref>{{citation |mode=cs1 |chapter-url=http://goldbook.iupac.org |title=The Gold Book |doi=10.1351/goldbook |access-date=September 16, 2012 |year= 2009 |isbn= 978-0-9678550-9-7 |chapter=Flavonoids (isoflavonoids and neoflavonoids)| veditors = Nič M, Jirát J, Košata B, Jenkins A, McNaught A |doi-access=free }}</ref>
they can be classified into:
*flavonoids or bioflavonoids
*[[isoflavonoid]]s, derived from 3-phenyl[[chromone|chromen-4-one]] (3-phenyl-1,4-[[benzopyran|benzopyrone]]) structure
*[[neoflavonoids]], derived from 4-phenyl[[coumarin]] (4-phenyl-1,2-[[benzopyran|benzopyrone]]) structure

The three flavonoid classes above are all [[ketone]]-containing compounds and as such, [[anthoxanthin]]s ([[flavone]]s and [[flavonol]]s).<ref name=lpi-flav/> 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.<ref name = "de_Souza_2021" /> Ring A usually shows a [[phloroglucinol]] substitution pattern.

== History ==
In the 1930s, [[Albert Szent-Györgyi]] and other scientists discovered that [[Vitamin C]] alone was not as effective at preventing [[scurvy]] as the crude yellow extract from oranges, lemons or paprika. They attributed the increased activity of this extract to the other substances in this mixture, which they referred to as "citrin" (referring to citrus) or "Vitamin P" (a reference to its effect on reducing the permeability of [[Capillary|capillaries]]). The substances in question ([[hesperidin]], [[eriodictyol]], hesperidin methyl chalcone and [[neohesperidin]]) were however later shown not to fulfil the criteria of a vitamin,<ref>{{Cite book|url=https://books.google.com/books?id=hc1TyKSumOkC&pg=PA210|title=Vitamins and Hormones|date=1949|publisher=Academic Press|isbn=978-0-08-086604-8|language=en}}</ref> so that this term is now obsolete.<ref>{{Cite book|vauthors=Clemetson AB|url=https://books.google.com/books?id=1kgPEAAAQBAJ&pg=PA101|title=Vitamin C: Volume I|date=January 10, 2018|publisher=CRC Press|isbn=978-1-351-08601-1|language=en}}</ref>

== Biosynthesis ==
{{Main|Flavonoid biosynthesis}}
Flavonoids are secondary metabolites synthesized mainly by plants. The general structure of flavonoids is a fifteen-carbon skeleton, containing two benzene rings connected by a three-carbon linking chain.<ref name=lpi-flav/> 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,  flavonols, flavanones, flavan-3-ols, flavanonols, flavones, and isoflavones.<ref name=lpi-flav/> Chalcones, also called [[chalconoids]], although lacking the heterocyclic ring, are also classified as flavonoids. 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.<ref name=lpi-flav/>

[[File:Flavonoids Biochemistry.png|500px|thumb|A biochemical diagram showing the class of flavonoids and their source in nature through various inter-related plant species.|center]]
{{Clearboth}}

==Functions of flavonoids in plants==
Flavonoids are widely distributed in plants, fulfilling many functions.<ref name=lpi-flav/> They are the most important [[Biological pigment|plant pigment]]s for flower coloration, producing yellow or red/blue pigmentation in petals evolved to attract [[pollinator]] animals. In higher plants, they 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 [[Symbiosis|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 factor]]s, 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''.<ref>{{cite journal|doi=10.1016/j.phytol.2007.10.001|title=Flavonoids from carnation (''Dianthus caryophyllus'') and their antifungal activity|year=2008| vauthors = Galeotti F, Barile E, Curir P, Dolci M, Lanzotti V |journal=Phytochemistry Letters|volume=1|issue=1 |pages=44–48|bibcode=2008PChL....1...44G }}</ref>

==Subgroups==
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<ref name="Ververidis">{{cite journal | vauthors = Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N | title = Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health | journal = Biotechnology Journal | volume = 2 | issue = 10 | pages = 1214–1234 | date = October 2007 | pmid = 17935117 | doi = 10.1002/biot.200700084 | s2cid = 24986941 }}</ref>):
[[File:Flavonoids.svg|400px|thumb|Flavonoids]]


===Anthocyanidins===
[[File:Flavylium cation.svg|thumb|right|Flavylium skeleton of anthocyanidins]]
[[Anthocyanidin]]s are the [[aglycone]]s of [[anthocyanin]]s; they use the '''[[flavylium]]''' (2-phenylchromenylium) ion skeleton.<ref name=lpi-flav/>
:'''Examples''': [[cyanidin]], [[delphinidin]], [[malvidin]], [[pelargonidin]], [[peonidin]], [[petunidin]]

===Anthoxanthins===
[[Anthoxanthin]]s are divided into two groups:<ref>{{cite journal|title=Isolation of a UDP-glucose: Flavonoid 5-''O''-glucosyltransferase gene and expression analysis of anthocyanin biosynthetic genes in herbaceous peony (''Paeonia lactiflora'' Pall.) |vauthors=Zhao DQ, Han CX, Ge JT, Tao J |journal=Electronic Journal of Biotechnology |date=November 15, 2012 |volume=15 |issue=6 |doi=10.2225/vol15-issue6-fulltext-7}}</ref>

:{| class="wikitable"
!rowspan=3|Group
!colspan=4|Skeleton
!rowspan=3|Examples
|-
!rowspan=2|Description
!colspan=2|Functional groups
!rowspan=2|Structural formula
|-
!|3-hydroxyl
!|2,3-dihydro
|-
|style="text-align:center"|'''[[Flavones|{{black|Flav}}{{Red|one}}]]'''
|style="text-align:center"|'''{{black|2-phenylchromen}}-{{Red|4-one}}'''
|style="text-align:center; font-size:x-large"|✗
|style="text-align:center; font-size:x-large"|✗
||[[Image:Flavone skeleton colored.svg]]
||[[Luteolin]], [[Apigenin]], [[Tangeritin]]
|-
|style="text-align:center"|'''[[Flavonols|{{black|Flav}}{{Red|on}}{{green|ol}}]]'''<br />or<br />'''[[Flavonols|{{green|3-hydroxy}}{{black|flav}}{{Red|one}}]]'''
|style="text-align:center"|'''{{green|3-hydroxy}}-{{black|2-phenylchromen}}-{{Red|4-one}}'''
|style="text-align:center; font-size:x-large"|✓
|style="text-align:center; font-size:x-large"|✗
||[[Image:Flavonol skeleton colored.svg]]
||[[Quercetin]], [[Kaempferol]], [[Myricetin]], [[Fisetin]], [[Galangin]], [[Isorhamnetin]], [[Pachypodol]], [[Rhamnazin]], [[Pyranoflavonol]]s, [[Furanoflavonol]]s,
|}

===Flavanones===
[[Flavanone]]s
{| class="wikitable"
!rowspan=3|Group
!colspan=4|Skeleton
!rowspan=3|Examples
|-
!rowspan=2|Description
!colspan=2|Functional groups
!rowspan=2|Structural formula
|-
!|3-hydroxyl
!|2,3-dihydro
|-
|style="text-align:center"|'''[[Flavanones|{{black|Flav}}{{blue|an}}{{Red|one}}]]'''
|style="text-align:center"|'''{{blue|2,3-dihydro}}-{{black|2-phenylchromen}}-{{Red|4-one}}'''
|style="text-align:center; font-size:x-large"|✗
|style="text-align:center; font-size:x-large"|✓
||[[Image:Flavanone skeleton colored.svg]]
||[[Hesperetin]], [[Naringenin]], [[Eriodictyol]], [[Homoeriodictyol]]
|}

===Flavanonols===
[[Flavanonol]]s
{| class="wikitable"
!rowspan=3|Group
!colspan=4|Skeleton
!rowspan=3|Examples
|-
!rowspan=2|Description
!colspan=2|Functional groups
!rowspan=2|Structural formula
|-
!|3-hydroxyl
!|2,3-dihydro
|-
|style="text-align:center"|'''[[Flavanonols|{{black|Flav}}{{blue|an}}{{Red|on}}{{green|ol}}]]'''<br />or<br />'''{{green|3-Hydroxy}}{{black|flav}}{{blue|an}}{{Red|one}}'''<br />or<br />'''{{blue|2,3-dihydro}}{{black|flav}}{{Red|on}}{{green|ol}}'''
|style="text-align:center"|'''{{green|3-hydroxy}}-{{blue|2,3-dihydro}}-{{black|2-phenylchromen}}-{{Red|4-one}}'''
|style="text-align:center; font-size:x-large"|✓
|style="text-align:center; font-size:x-large"|✓
||[[Image:Flavanonol skeleton colored.svg]]
||[[Taxifolin]] (or [[Dihydroquercetin]]), [[Dihydrokaempferol]]
|}

===Flavans===
[[File:Flavan acsv.svg|thumb|right|Flavan structure]]
Include [[flavan-3-ol]]s (flavanols), [[flavan-4-ol]]s, and [[flavan-3,4-diol]]s.
{| class="wikitable"
|-
! Skeleton
! Name
<!-- ! header 3 -->
|-
| [[File:Flavan-3-ol.svg|100px|Flavan-3ol]]
| [[Flavan-3-ol]] (flavanol)
<!--|row 1, cell 3 -->
|-
| [[File:Flavan-4-ol.svg|100px|Flavan-4ol]]
| [[Flavan-4-ol]]
<!--|row 2, cell 3 -->
|-
| [[File:Flavan-3,4-diol.svg|100px|Flavan-3,4-diol]]
| [[Flavan-3,4-diol]] (leucoanthocyanidin)
<!--|row 3, cell 3 -->
|}
*'''[[Flavan-3-ols]] (flavanols)'''
** [[Flavan-3-ols|Flav<u>an</u>-''3-ols'']] use the 2-phenyl-<u>3,4-dihydro</u>-2''H''-chromen-''3-ol'' skeleton
*:'''Examples''': [[catechin]] (C), [[gallocatechin]] (GC), [[catechin 3-gallate]] (Cg), [[gallocatechin 3-gallate]] (GCg), [[epicatechin]]s (EC), [[epigallocatechin]] (EGC), [[epicatechin 3-gallate]] (ECg), [[epigallocatechin 3-gallate]] (EGCg)
** [[Theaflavin]]
*:'''Examples''': [[theaflavin-3-gallate]], [[theaflavin-3'-gallate]], [[theaflavin-3,3'-digallate]]
** [[Thearubigin]]
** [[Proanthocyanidins]] are dimers, trimers, oligomers, or polymers of the flavanols

===Isoflavonoids===
*[[Isoflavonoid]]s
**[[Isoflavone]]s use the 3-phenylchromen-''4-one'' skeleton (with no hydroxyl group substitution on carbon at position 2) 
*:'''Examples''': [[Genistein]], [[Daidzein]], [[Glycitein]]
**[[Isoflavane]]s
**[[Isoflavandiol]]s
**[[Isoflavene]]s
**[[Coumestan]]s
**[[Pterocarpan]]s

==Dietary sources==
[[Image:Parsley100.jpg|thumb|Parsley is a source of [[flavones]]]]
[[Image:PattsBlueberries.jpg|thumb|Blueberries are a source of dietary anthocyanins]]
[[Image:Grapefruit Schnitt 2008-3-3.JPG|thumb|Flavonoids are found in [[citrus]] fruits, including red [[grapefruit]]]]

Flavonoids (specifically flavanoids such as the [[catechins]]) are "the most common group of [[polyphenol]]ic compounds in the human diet and are found ubiquitously in plants".<ref name=lpi-flav/><ref>{{cite journal | vauthors = Spencer JP | title = Flavonoids: modulators of brain function? | journal = The British Journal of Nutrition | volume = 99 |issue= E Suppl 1 | pages = ES60–ES77 | date = May 2008 | pmid = 18503736 | doi = 10.1017/S0007114508965776 | doi-access = free }}</ref> 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 [[Chemical compound|compounds]] (for instance [[alkaloids]]) mean that many animals, including [[Human nutrition|humans]], ingest significant quantities in their diet.<ref name=lpi-flav/> 

Foods with a high flavonoid content include [[parsley]], [[onion]]s, [[blueberries]] and [[strawberry|strawberries]], [[black tea]], [[banana]]s, and [[citrus]] fruits.<ref name="ars.usda">{{cite web |url=http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Articles/AICR06_flav.pdf|title=Sources of Flavonoids in the U.S. Diet Using USDA’s Updated Database on the Flavonoid Content of Selected Foods|publisher=Agricultural Research Service, US Department of Agirculture|date=2006}}</ref> One study found high flavonoid content in [[buckwheat]].<ref>{{Cite journal| vauthors = Oomah BD, Mazza G |title=Flavonoids and Antioxidative Activities in Buckwheat|journal=Journal of Agricultural and Food Chemistry|volume=44|issue=7|pages=1746–1750 |doi=10.1021/jf9508357 |year=1996}}</ref>

Citrus flavonoids include [[hesperidin]] (a glycoside of the flavanone [[hesperetin]]), [[quercitrin]], [[rutin]] (two [[glycoside]]s of quercetin, and the flavone [[tangeritin]]. The flavonoids are less concentrated in the [[Juice vesicles|pulp]] than in the [[Peel (fruit)|peels]] (for example, 165 versus 1156&nbsp;mg/100&nbsp;g in pulp versus peel of [[Citrus unshiu|satsuma mandarin]], and 164 vis-à-vis 804&nbsp;mg/100&nbsp;g in pulp versus peel of [[clementine]]).<ref>{{cite journal|url=http://www.agr.unizg.hr/smotra/pdf_74/acs74_38.pdf|title=Determination of flavonoids in pulp and peel of mandarin fruits (table 1)|page=223|journal=Agriculturae Conspectus Scientificus|year=2009|volume=74|number=3|vauthors=Levaj B|display-authors=etal|access-date=2020-07-31|archive-date=2017-08-10|archive-url=https://web.archive.org/web/20170810141820/http://www.agr.unizg.hr/smotra/pdf_74/acs74_38.pdf|url-status=dead}}</ref>

[[Peanut]] (red) skin contains significant polyphenol content, including flavonoids.<ref>{{cite journal | vauthors = De Camargo AC, Regitano-d'Arce MA, Gallo CR, Shahidi F | year = 2015 | title = Gamma-irradiation induced changes in microbiological status, phenolic profile and antioxidant activity of peanut skin | journal = Journal of Functional Foods | volume = 12 | pages = 129–143 | doi=10.1016/j.jff.2014.10.034| doi-access = free }}</ref><ref>{{cite journal | vauthors = Chukwumah Y, Walker LT, Verghese M | title = Peanut skin color: a biomarker for total polyphenolic content and antioxidative capacities of peanut cultivars | journal = International Journal of Molecular Sciences | volume = 10 | issue = 11 | pages = 4941–4952 | date = November 2009 | pmid = 20087468 | pmc = 2808014 | doi = 10.3390/ijms10114941 | doi-access = free }}</ref>

:{| class="wikitable"
|+Flavonoid content in food (mg/100&nbsp;g)<ref name=lpi-flav/>
! 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
|}

==Dietary intake==
[[File:Flavonoid intake of adults (18 to 64 years) in the European Union.png|thumb|300px|Mean flavonoid intake in mg/d per country, the pie charts show the relative contribution of different types of flavonoids.<ref name=Vogiatzoglou_2015/>]]

[[Food composition data]] for flavonoids were provided by the [[USDA]] database on flavonoids.<ref name="ars.usda" /> In the United States [[NHANES]] survey, mean flavonoid intake was 190&nbsp;mg per day in adults, with [[flavan-3-ol]]s as the main contributor.<ref name="Chun_2007">{{cite journal | vauthors = Chun OK, Chung SJ, Song WO | title = Estimated dietary flavonoid intake and major food sources of U.S. adults | journal = The Journal of Nutrition | volume = 137 | issue = 5 | pages = 1244–1252 | date = May 2007 | pmid = 17449588 | doi = 10.1093/jn/137.5.1244 | doi-access = free }}</ref> In the [[European Union]], based on data from [[EFSA]], mean flavonoid intake was 140&nbsp;mg/d, although there were considerable differences among individual countries.<ref name="Vogiatzoglou_2015">{{cite journal | vauthors = Vogiatzoglou A, Mulligan AA, Lentjes MA, Luben RN, Spencer JP, Schroeter H, Khaw KT, Kuhnle GG | display-authors = 6 | title = Flavonoid intake in European adults (18 to 64 years) | journal = PLOS ONE | volume = 10 | issue = 5 | pages = e0128132 | year = 2015 | pmid = 26010916 | pmc = 4444122 | doi = 10.1371/journal.pone.0128132 | bibcode = 2015PLoSO..1028132V | doi-access = free }}</ref> The main type of flavonoids consumed in the EU and USA were flavan-3-ols (80% for USA adults), mainly from tea or cocoa in chocolate, while intake of other flavonoids was considerably lower.<ref name=lpi-flav/><ref name=Vogiatzoglou_2015/><ref name=Chun_2007/>
[[File:Main types and sources of flavonoids consumed by adults (18 to 64 years) in the European Union.png|thumb|300px|Data are based on mean flavonoid intake of all countries included in the 2011 EFSA Comprehensive European Food Consumption Database.<ref name=Vogiatzoglou_2015/>]]

== Research ==
Neither the United States [[Food and Drug Administration]] (FDA) nor the [[European Food Safety Authority]] (EFSA) has approved any flavonoids as [[prescription drug]]s.<ref name=lpi-flav/><ref>{{cite web |url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm|archive-url=https://web.archive.org/web/20031011113245/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm|url-status=dead|archive-date=October 11, 2003|title=FDA approved drug products |publisher=US Food and Drug Administration|access-date=November 8, 2013}}</ref><ref>{{cite web |url=https://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm2006876.htm#Approved_Health_Claims|archive-url=https://web.archive.org/web/20130804234315/http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm2006876.htm#Approved_Health_Claims|url-status=dead|archive-date=August 4, 2013|title=Health Claims Meeting Significant Scientific Agreement |publisher=US Food and Drug Administration |access-date=November 8, 2013}}</ref><ref name="EFSA2010">{{cite journal |author=EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) |title=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|journal= EFSA Journal|year= 2010|volume= 8|issue=2|page=1489|doi=10.2903/j.efsa.2010.1489|doi-access=free}}</ref> The U.S. FDA has warned numerous dietary supplement and food manufacturers, including [[Unilever]], producer of [[Lipton|Lipton tea]] in the U.S., about illegal advertising and misleading [[Health claim|health claims]] regarding flavonoids, such as that they lower cholesterol or relieve pain.<ref>{{cite news |url=https://www.npr.org/sections/health-shots/2010/09/07/129701566/fda-to-lipton-tea-can-t-do-that |title=FDA To Lipton: Tea Can't Do That |author=Hensley S |date=September 7, 2010 |website=[[National Public Radio|NPR]] |access-date=June 17, 2023}}</ref><ref>{{cite news |url=https://theproducenews.com/cherry-companies-warned-fda-against-making-health-claims |title=Cherry companies warned by FDA against making health claims |author=<!--Not stated--> |date=November 1, 2005 |website=The Produce News |access-date=June 17, 2023}}</ref>

===Metabolism and excretion===
Flavonoids are poorly absorbed in the human body (less than 5%), then are quickly metabolized into smaller fragments with unknown properties, and rapidly excreted.<ref name=lpi-flav/><ref name=EFSA2010/><ref>{{cite journal | vauthors = Lotito SB, Frei B | title = Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? | journal = Free Radical Biology & Medicine | volume = 41 | issue = 12 | pages = 1727–1746 | date = December 2006 | pmid = 17157175 | doi = 10.1016/j.freeradbiomed.2006.04.033 }}</ref><ref>{{cite journal | vauthors = Williams RJ, Spencer JP, Rice-Evans C | title = Flavonoids: antioxidants or signalling molecules? | journal = Free Radical Biology & Medicine | volume = 36 | issue = 7 | pages = 838–849 | date = April 2004 | pmid = 15019969 | doi = 10.1016/j.freeradbiomed.2004.01.001 }}</ref> 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 by production of [[uric acid]] resulting from flavonoid [[depolymerization]] and [[excretion]].<ref name=lpi-flav/> Microbial metabolism is a major contributor to the overall metabolism of dietary flavonoids.<ref name=lpi-flav/><ref>{{cite journal | vauthors = Hidalgo M, Oruna-Concha MJ, Kolida S, Walton GE, Kallithraka S, Spencer JP, de Pascual-Teresa S | title = Metabolism of anthocyanins by human gut microflora and their influence on gut bacterial growth | journal = Journal of Agricultural and Food Chemistry | volume = 60 | issue = 15 | pages = 3882–3890 | date = April 2012 | pmid = 22439618 | doi = 10.1021/jf3002153 }}</ref>

===Inflammation===
[[Inflammation]] has been implicated as a possible origin of numerous local and systemic diseases, such as [[cancer]],<ref>{{cite journal | vauthors = Ravishankar D, Rajora AK, Greco F, Osborn HM | title = Flavonoids as prospective compounds for anti-cancer therapy | journal = The International Journal of Biochemistry & Cell Biology | volume = 45 | issue = 12 | pages = 2821–2831 | date = December 2013 | pmid = 24128857 | doi = 10.1016/j.biocel.2013.10.004 }}</ref> [[cardiovascular disorders]],<ref>{{cite journal | vauthors = Manach C, Mazur A, Scalbert A | title = Polyphenols and prevention of cardiovascular diseases | journal = Current Opinion in Lipidology | volume = 16 | issue = 1 | pages = 77–84 | date = February 2005 | pmid = 15650567 | doi = 10.1097/00041433-200502000-00013 | s2cid = 794383 }}</ref> [[diabetes mellitus]],<ref>{{cite journal | vauthors = Babu PV, Liu D, Gilbert ER | title = Recent advances in understanding the anti-diabetic actions of dietary flavonoids | journal = The Journal of Nutritional Biochemistry | volume = 24 | issue = 11 | pages = 1777–1789 | date = November 2013 | pmid = 24029069 | pmc = 3821977 | doi = 10.1016/j.jnutbio.2013.06.003 }}</ref> and [[Coeliac disease|celiac disease]].<ref>{{cite journal | vauthors = Ferretti G, Bacchetti T, Masciangelo S, Saturni L | title = Celiac disease, inflammation and oxidative damage: a nutrigenetic approach | journal = Nutrients | volume = 4 | issue = 4 | pages = 243–257 | date = April 2012 | pmid = 22606367 | pmc = 3347005 | doi = 10.3390/nu4040243 | doi-access = free }}</ref> There is no [[evidence-based medicine|clinical evidence]] that dietary flavonoids affect any of these diseases.<ref name=lpi-flav/>

===Cancer===
[[Clinical trial|Clinical studies]] investigating the relationship between flavonoid consumption and cancer prevention or development are conflicting for most types of cancer, probably because most human studies have weak designs, such as a small [[Sample size determination|sample size]].<ref name=lpi-flav/><ref name="ReferenceA">{{cite journal | vauthors = Romagnolo DF, Selmin OI | title = Flavonoids and cancer prevention: a review of the evidence | journal = Journal of Nutrition in Gerontology and Geriatrics | volume = 31 | issue = 3 | pages = 206–238 | year = 2012 | pmid = 22888839 | doi = 10.1080/21551197.2012.702534 | s2cid = 205960210 }}</ref> There is little evidence to indicate that dietary flavonoids affect human cancer risk in general.<ref name=lpi-flav/>

===Cardiovascular diseases===

Although no significant association has been found between flavan-3-ol intake and cardiovascular disease mortality, clinical trials have shown improved [[endothelial dysfunction|endothelial function]] and reduced [[blood pressure]] (with a few studies showing inconsistent results).<ref name=lpi-flav/> Reviews of [[prospective cohort study|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.<ref name=lpi-flav/><ref>{{cite journal | vauthors = Wang X, Ouyang YY, Liu J, Zhao G | title = Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies | journal = The British Journal of Nutrition | volume = 111 | issue = 1 | pages = 1–11 | date = January 2014 | pmid = 23953879 | doi = 10.1017/S000711451300278X | doi-access = free }}</ref>

In 2013, the EFSA decided to permit health claims that 200 mg/day of cocoa flavanols "help[s] maintain the elasticity of blood vessels."<ref>{{cite journal |author=<!--Staff writer(s); no by-line.--> |date=June 27, 2012 |title=Scientific Opinion on the substantiation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/2006 |url=https://www.efsa.europa.eu/pt/efsajournal/pub/2809 |journal=EFSA Journal |volume=10 |issue=7 |doi=10.2903/j.efsa.2012.2809 |access-date=June 17, 2023|url-access=subscription }}</ref><ref>{{cite web |url=https://www.confectionerynews.com/Article/2013/09/04/Cocoa-flavanol-health-claim-becomes-EU-law |title=Cocoa flavanol health claim becomes EU law |author=<!--Staff writer(s); no by-line.--> |date=September 4, 2013 |website=Confectionary News |access-date=June 17, 2023}}</ref> The FDA followed suit in 2023, stating that there is "supportive, but not conclusive" evidence that 200&nbsp;mg per day of cocoa flavanols can reduce the risk of cardiovascular disease. This is greater than the levels found in typical chocolate bars, which can also contribute to weight gain, potentially harming cardiovascular health.<ref>{{cite report |author=Kavanaugh C |date=February 1, 2023 |title=RE: Petition for a Qualified Health Claim – for Cocoa Flavanols and Reduced Risk of Cardiovascular Disease (Docket No. FDA-2019-Q-0806)
 |url=https://www.fda.gov/media/165090/download |publisher=FDA}}</ref><ref>{{cite news |url=https://www.npr.org/sections/health-shots/2023/02/12/1156044919/chocolate-heart-health-flavanols |title=Is chocolate good for your heart? Finally the FDA has an answer – kind of |author=Aubrey A |date=February 12, 2023 |website=[[National Public Radio|NPR]] |access-date=June 17, 2023}}</ref>

== Synthesis, detection, quantification, and semi-synthetic alterations ==

=== Color spectrum ===
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 [[carotenoid]]s, [[Flavin group|flavins]], [[cryptochrome]]s in addition to phytochromes. The [[Photomorphogenesis|photomorphogenic]] process of phytochrome-mediated flavonoid biosynthesis has been observed in [[Amaranth|''Amaranthus'']], [[barley]], [[maize]], ''[[Sorghum]]'' and [[turnip]]. Red light promotes flavonoid synthesis.<ref>{{Cite book|title = Modern Plant Physiology|url = https://books.google.com/books?id=03S6VbTjCmUC|publisher = CRC Press|date = January 2004|isbn = 9780849317149|language = en | vauthors = Sinha RK |page = 457}}</ref>

=== Availability through microorganisms ===
Research has shown production of flavonoid molecules from genetically engineered microorganisms.<ref name="trantas09">{{cite journal | vauthors = Trantas E, Panopoulos N, Ververidis F | title = Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae | journal = Metabolic Engineering | volume = 11 | issue = 6 | pages = 355–366 | date = November 2009 | pmid = 19631278 | doi = 10.1016/j.ymben.2009.07.004 }}</ref><ref name="Ververidis2">{{cite journal | vauthors = Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N | title = Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part II: Reconstruction of multienzyme pathways in plants and microbes | journal = Biotechnology Journal | volume = 2 | issue = 10 | pages = 1235–1249 | date = October 2007 | pmid = 17935118 | doi = 10.1002/biot.200700184 | s2cid = 5805643 }}</ref>

=== Tests for detection ===
====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.<ref>{{cite journal|vauthors=Yisa J |title=Phytochemical Analysis and Antimicrobial Activity of ''Scoparia dulcis'' and ''Nymphaea lotus''|url=http://connection.ebscohost.com/c/articles/51366872/phytochemical-analysis-antimicrobial-activity-scoparia-dulcis-nymphaea-lotus|archive-url=https://web.archive.org/web/20131017003142/http://connection.ebscohost.com/c/articles/51366872/phytochemical-analysis-antimicrobial-activity-scoparia-dulcis-nymphaea-lotus|url-status=dead|archive-date=October 17, 2013|journal=Australian Journal of Basic and Applied Sciences|year= 2009|volume= 3|issue=4|pages=3975–3979}}</ref> Colours varying from orange to red indicated [[flavone]]s, red to crimson indicated flavonoids, crimson to magenta indicated [[flavonone]]s.

====Sodium hydroxide test====
About 5&nbsp;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.<ref>{{cite journal | vauthors = Bello IA, Ndukwe GI, Audu OT, Habila JD | title = A bioactive flavonoid from ''Pavetta crassipes'' K. Schum. | journal = Organic and Medicinal Chemistry Letters | volume = 1 | issue = 1 | pages = 14 | date = October 2011 | pmid = 22373191 | pmc = 3305906 | doi = 10.1186/2191-2858-1-14 | doi-access = free }}</ref>

====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.<ref>{{cite journal | doi = 10.1002/j.2050-0416.1985.tb04303.x | volume=91 | year=1985 | journal=Journal of the Institute of Brewing | pages=37–40 | vauthors=Delcour JA| title=A New Colourimetric Assay for Flavanoids in Pilsner Beers | doi-access=free }}</ref>

=== Quantification ===
Lamaison and Carnet have designed a test for the determination of the total flavonoid content of a sample (AlCI<sub>3</sub> method). After proper mixing of the sample and the reagent, the mixture is incubated for ten minutes at ambient temperature and the absorbance of the solution is read at 440&nbsp;nm. Flavonoid content is expressed in mg/g of [[quercetin]].<ref>{{cite journal|vauthors=Lamaison JL, Carnet A |title=Teneurs en principaux flavonoïdes des fleurs de ''Cratageus monogyna'' Jacq. et de ''Cratageus laevigata'' (Poiret D.C.) en fonction de la végétation|trans-title=Principal flavonoid content of flowers of ''Cratageus monogyna'' Jacq. and ''Cratageus laevigata'' (Poiret D.C.) dependent on vegetation|lang=French|journal=Plantes Medicinales: Phytotherapie|year= 1991|volume =25| pages= 12–16}}</ref><ref>{{Cite journal |last=Khokhlova |first=Kateryna |last2=Zdoryk |first2=Oleksandr |last3=Vyshnevska |first3=Liliia |date=January 2020 |title=Chromatographic characterization on flavonoids and triterpenes of leaves and flowers of 15 crataegus L. species |url=https://pubmed.ncbi.nlm.nih.gov/30417671/ |journal=Natural Product Research |volume=34 |issue=2 |pages=317–322 |doi=10.1080/14786419.2018.1528589 |issn=1478-6427 |pmid=30417671}}</ref>

=== Semi-synthetic alterations ===
Immobilized ''[[Candida antarctica]]'' lipase can be used to catalyze the [[Regioselectivity|regioselective]] [[acylation]] of flavonoids.<ref>{{cite journal | vauthors = Passicos E, Santarelli X, Coulon D | title = Regioselective acylation of flavonoids catalyzed by immobilized ''Candida antarctica'' lipase under reduced pressure | journal = Biotechnology Letters | volume = 26 | issue = 13 | pages = 1073–1076 | date = July 2004 | pmid = 15218382 | doi = 10.1023/B:BILE.0000032967.23282.15 | s2cid = 26716150 }}</ref>

== See also ==

* [[Phytochemical]]
* [[List of antioxidants in food]]
* [[List of phytochemicals in food]]
* [[Phytochemistry]]
* [[Secondary metabolites]]
* [[Homoisoflavonoid]]s, related chemicals with a 16 carbons skeleton

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Andersen ØM, Markham KR |title=Flavonoids: Chemistry, Biochemistry and Applications |date=2006 |publisher=CRC Press, Taylor & Francis |location=Boca Raton, FL |isbn=978-0-8493-2021-7}}
* {{cite book | vauthors = Grotewold E |title=The science of flavonoids |date=2006 |publisher=Springer |location=New York |isbn = 978-0-387-74550-3 }}
* {{cite book | title = Comparative Biochemistry of the Flavonoids | vauthors = Harborne JB | date = 1967 | url = https://books.google.com/books?id=CyTf2oObc7cC }}
* {{cite journal | doi = 10.1016/0022-2860(71)87109-0 | volume=10 | title=The systematic identification of flavonoids | year=1971 | journal=Journal of Molecular Structure | page=320| vauthors=Mabry TJ, Markham KR, Thomas MB | issue=2 }}
{{refend}}
{{Commons category|Flavonoids}}

===Databases===
* [http://www.ars.usda.gov/Services/docs.htm?docid=6231 USDA Database for the Flavonoid Content of Selected Foods, Release 3.1 (December 2013); data for 506 foods in the 5 subclasses of flavonoids provided in a separate PDF updated May 2014]
* [http://bioinfo.net.in/flavodb/home.html FlavoDB, Bioinformatics Centre, India, November 2019]

{{Flavonoids}}
{{Phenylpropanoids}}
{{Polyphenol}}

{{Authority control}}

[[Category:Flavonoids| ]]
[[Category:Nutrients]]
[[Category:Nutrition]]
[[Category:Flavonoid antioxidants]]
[[Category:Wood extracts]]