View source for Apigenin

{{Short description|Chemical in plants}}
{{Use American English|date=May 2025}}
{{Use dmy dates|date=May 2025}}
{{cs1 config|name-list-style=vanc|display-authors=3}}
{{chembox
| Watchedfields = changed
| verifiedrevid = 443662850
| Name = Apigenin
| Reference =<ref>''[[Merck Index]]'', 11th Edition, '''763'''.</ref>
| ImageFile = Apigenin.svg
| ImageClass = skin-invert-image
| ImageFile2 = Apigenin-3D-balls.png
| ImageSize = 
| ImageName = Apigenin
| IUPACName = 4′,5,7-Trihydroxyflavone
| SystematicName = 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4''H''-1-benzopyran-4-one
| OtherNames =Apigenine; Chamomile; Apigenol; Spigenin; Versulin; C.I. Natural Yellow 1
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4136
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4444100
| EC_number = 208-292-3 
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C01477
| InChI = 1/C15H10O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-7,16-18H
| InChIKey = KZNIFHPLKGYRTM-UHFFFAOYAX
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 28
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C15H10O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-7,16-18H
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KZNIFHPLKGYRTM-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 520-36-5
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 7V515PI7F6
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 18388
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB07352
| SMILES = O=C\1c3c(O/C(=C/1)c2ccc(O)cc2)cc(O)cc3O
| PubChem = 5280443
  }}
|Section2={{Chembox Properties
| Appearance = Yellow crystalline solid
| C=15 | H=10 | O=5
| MeltingPtC = 345 to 350
| MeltingPt_notes = 
| LambdaMax = 267, 296sh, 336 nm in methanol<ref>The Systematic Identification of Flavonoids. Mabry et al, 1970, page 81</ref>
  }}
}}

'''Apigenin''' (4′,5,7-trihydroxyflavone), found in many plants, is a [[flavone]] compound that is the [[aglycone]] of several naturally occurring [[glycosides]]. It is a yellow crystalline solid that has been used to dye wool.

Apigenin is abundant in [[parsley]], [[celery]], [[celeriac]], and [[chamomile]] [[Flower|flowers]]. It occurs in many fruits and vegetables, with the highest concentrations in dried and fresh parsley.

==Sources in nature==
Apigenin is found in many fruits and vegetables, but parsley, celery, [[celeriac]], and chamomile tea are the most common sources. Apigenin is particularly abundant in the flowers of chamomile plants, constituting 68% of total [[flavonoid]]s.<ref name="pmid26487830">{{cite journal | vauthors = Venigalla M, Gyengesi E, Münch G | title = Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease | journal = Neural Regeneration Research | volume = 10 | issue = 8 | pages = 1181–5 | date = August 2015 | pmid = 26487830 | pmc = 4590215 | doi = 10.4103/1673-5374.162686 | doi-access = free }}</ref> Dried parsley can contain about 45&nbsp;[[Kilogram#SI multiples|mg]]&nbsp;apigenin per gram. The apigenin content of fresh parsley is reportedly 215&nbsp;mg per 100 grams, which is much higher than the next highest food source.<ref name="lpi-flav">{{cite web|title = Flavonoids | url=http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids|publisher=[[Linus Pauling Institute]], Oregon State University |access-date=2021-01-26|date=November 2015}}</ref>

== Pharmacology ==
[[In vitro|''In vitro'']], apigenin binds competitively to the [[benzodiazepine]] site on [[GABAA receptor|GABA<sub>A</sub>]] receptors.<ref>{{Cite journal |last1=Viola |first1=H. |last2=Wasowski |first2=C. |last3=Levi de Stein |first3=M. |last4=Wolfman |first4=C. |last5=Silveira |first5=R. |last6=Dajas |first6=F. |last7=Medina |first7=J. H. |last8=Paladini |first8=A. C. |date=June 1995 |title=Apigenin, a component of ''Matricaria recutita'' flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects |url=https://pubmed.ncbi.nlm.nih.gov/7617761/ |journal=Planta Medica |volume=61 |issue=3 |pages=213–216 |doi=10.1055/s-2006-958058 |issn=0032-0943 |pmid=7617761}}</ref> There exist conflicting findings regarding how apigenin interacts with this site.<ref>{{Cite journal |last1=Dekermendjian |first1=K. |last2=Kahnberg |first2=P. |last3=Witt |first3=M. R. |last4=Sterner |first4=O. |last5=Nielsen |first5=M. |last6=Liljefors |first6=T. |date=1999-10-21 |title=Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex |url=https://pubmed.ncbi.nlm.nih.gov/10543878/ |journal=Journal of Medicinal Chemistry |volume=42 |issue=21 |pages=4343–4350 |doi=10.1021/jm991010h |issn=0022-2623 |pmid=10543878}}</ref><ref>{{Cite journal |last1=Avallone |first1=R. |last2=Zanoli |first2=P. |last3=Puia |first3=G. |last4=Kleinschnitz |first4=M. |last5=Schreier |first5=P. |last6=Baraldi |first6=M. |date=2000-06-01 |title=Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla |url=https://pubmed.ncbi.nlm.nih.gov/10751547/ |journal=Biochemical Pharmacology |volume=59 |issue=11 |pages=1387–1394 |doi=10.1016/s0006-2952(00)00264-1 |issn=0006-2952 |pmid=10751547|hdl=11380/1207274 |hdl-access=free }}</ref>

== Biosynthesis ==
Apigenin is biosynthetically derived from the general [[Phenylpropanoids metabolism|phenylpropanoid pathway]] and the flavone synthesis pathway.<ref>{{Cite journal|last=Forkmann|first=G.|date=January 1991|title=Flavonoids as Flower Pigments: The Formation of the Natural Spectrum and its Extension by Genetic Engineering|journal=Plant Breeding|language=en|volume=106|issue=1|pages=1–26|doi=10.1111/j.1439-0523.1991.tb00474.x|issn=0179-9541|doi-access=free}}</ref> The phenylpropanoid pathway starts from the aromatic amino acids L-phenylalanine or [[L-tyrosine]], both products of the [[Shikimate pathway]].<ref>{{cite journal | vauthors = Herrmann KM | title = The shikimate pathway as an entry to aromatic secondary metabolism | journal = Plant Physiology | volume = 107 | issue = 1 | pages = 7–12 | date = January 1995 | pmid = 7870841 | pmc = 161158 | doi = 10.1104/pp.107.1.7 }}</ref>  When starting from L-phenylalanine, first the amino acid is non-oxidatively deaminated by [[Phenylalanine ammonia-lyase|phenylalanine ammonia lyase]] to make cinnamate, followed by oxidation at the ''para'' position by [[Trans-cinnamate 4-monooxygenase|cinnamate 4-hydroxylase]] to produce ''p''-coumarate. As L-tyrosine is already oxidized at the ''para'' position, it skips this oxidation and is simply deaminated by [[Tyrosine ammonia-lyase|tyrosine ammonia lyase]] to arrive at ''p''-coumarate.<ref>{{cite journal | vauthors = Lee H, Kim BG, Kim M, Ahn JH | title = Biosynthesis of Two Flavones, Apigenin and Genkwanin, in Escherichia coli | journal = Journal of Microbiology and Biotechnology | volume = 25 | issue = 9 | pages = 1442–8 | date = September 2015 | pmid = 25975614 | doi = 10.4014/jmb.1503.03011 | doi-access = free }}</ref> To complete the general phenylpropanoid pathway, [[4-Coumarate-CoA ligase|4-coumarate CoA ligase]] substitutes coenzyme A at the carboxy group of ''p''-coumarate. Entering the flavone synthesis pathway, the type III [[polyketide synthase]] enzyme [[chalcone synthase]] uses consecutive condensations of three equivalents of [[malonyl-CoA]] followed by aromatization to convert ''p''-coumaroyl-CoA to [[chalcone]].<ref>{{cite journal | vauthors = Austin MB, Noel JP | title = The chalcone synthase superfamily of type III polyketide synthases | journal = Natural Product Reports | volume = 20 | issue = 1 | pages = 79–110 | date = February 2003 | pmid = 12636085 | doi = 10.1039/b100917f | citeseerx = 10.1.1.131.8158 }}</ref> [[Chalcone isomerase]] then isomerizes the product to close the pyrone ring to make [[naringenin]]. Finally, a flavanone synthase enzyme oxidizes naringenin to apigenin.<ref>{{cite journal | vauthors = Martens S, Forkmann G, Matern U, Lukacin R | title = Cloning of parsley flavone synthase I | journal = Phytochemistry | volume = 58 | issue = 1 | pages = 43–6 | date = September 2001 | pmid = 11524111 | doi = 10.1016/S0031-9422(01)00191-1 | bibcode = 2001PChem..58...43M }}</ref> Two types of flavone synthase (FNS) have been described; FNS I, a soluble enzyme that uses 2-oxogluturate, Fe<sup>2+</sup>, and ascorbate as cofactors and FNS II, a membrane bound, NADPH dependent cytochrome p450 monooxygenase.<ref>{{cite journal | vauthors = Leonard E, Yan Y, Lim KH, Koffas MA | title = Investigation of two distinct flavone synthases for plant-specific flavone biosynthesis in ''Saccharomyces cerevisiae'' | journal = Applied and Environmental Microbiology | volume = 71 | issue = 12 | pages = 8241–8 | date = December 2005 | pmid = 16332809 | pmc = 1317445 | doi = 10.1128/AEM.71.12.8241-8248.2005 | bibcode = 2005ApEnM..71.8241L }}</ref>

== Glycosides ==
The naturally occurring glycosides formed by the combination of apigenin with sugars include:{{cn|date=May 2025}}

* [[Apiin]] (apigenin 7-''O''-apioglucoside), isolated from [[parsley]]<ref>{{cite journal | vauthors = Meyer H, Bolarinwa A, Wolfram G, Linseisen J | title = Bioavailability of apigenin from apiin-rich parsley in humans | journal = Annals of Nutrition & Metabolism | volume = 50 | issue = 3 | pages = 167–72 | year = 2006 | pmid = 16407641 | doi = 10.1159/000090736 | s2cid = 8223136 | url = https://nbn-resolving.org/urn:nbn:de:bvb:384-opus4-857673 | url-access = subscription }}</ref> and celery
* [[Apigetrin]] (apigenin 7-[[glucoside]]), found in [[dandelion coffee]]
* [[Vitexin]] (apigenin 8-''C''-glucoside)
* [[Isovitexin]] (apigenin 6-''C''-glucoside)
* [[Rhoifolin]] (apigenin 7-''O''-[[neohesperidoside]])
* Schaftoside (apigenin 6-''C''-glucoside 8-''C''-[[arabinoside]])

==In diet==
Some foods contain relatively high amounts of apigenin:<ref name="Ref_USDA">[https://www.ars.usda.gov/ARSUserFiles/80400525/Data/Flav/Flav_R03.pdf  USDA Database for the Flavonoid Content of Selected Foods, Release 3 (2011)]</ref>

{| class="wikitable"
|-
! Product
! Apigenin<br /><small>(milligrams per 100 grams)</small>
|-
| Parsley, dried
| 4503.5
|-
| Parsley, fresh
| 215.5
|-
| Celery hearts, green
| 19.1
|-
| [[Rutabaga|Rutabagas, raw]]
| 4
|}

== See also ==
* [[Amentoflavone]]

== References ==
{{Reflist}}

{{Flavone}}
{{Phytoestrogens}}
{{Adenosinergics}}
{{Estrogenics}}
{{GABAAR PAMs}}
{{Glutamatergics}}
{{Opioidergics}}
{{Progestogenics}}

[[Category:Aromatase inhibitors]]
[[Category:Delta-opioid receptor antagonists]]
[[Category:Flavones]]
[[Category:GABAA receptor positive allosteric modulators]]
[[Category:Resorcinols]]
[[Category:Kappa-opioid receptor antagonists]]
[[Category:Mu-opioid receptor antagonists]]
[[Category:NMDA receptor antagonists]]
[[Category:Phytoestrogens]]
[[Category:Progestogens]]
[[Category:Triols]]