apigenin

{{chembox

| Watchedfields = changed

| verifiedrevid = 443662850

| Name = Apigenin

| Reference =Merck Index, 11th Edition, 763.

| 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)-4H-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 methanolThe Systematic Identification of Flavonoids. Mabry et al, 1970, page 81

}}

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 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 flavonoids.{{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 }} Dried parsley can contain about 45 mg apigenin per gram. The apigenin content of fresh parsley is reportedly 215 mg per 100 grams, which is much higher than the next highest food source.{{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}}

Pharmacology

In vitro, apigenin binds competitively to the benzodiazepine site on GABA_A receptors.{{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}} There exist conflicting findings regarding how apigenin interacts with this site.{{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}}{{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}}

Biosynthesis

Apigenin is biosynthetically derived from the general phenylpropanoid pathway and the flavone synthesis pathway.{{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}} The phenylpropanoid pathway starts from the aromatic amino acids L-phenylalanine or L-tyrosine, both products of the Shikimate pathway.{{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 }} When starting from L-phenylalanine, first the amino acid is non-oxidatively deaminated by phenylalanine ammonia lyase to make cinnamate, followed by oxidation at the para position by 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 to arrive at p-coumarate.{{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 }} To complete the general phenylpropanoid pathway, 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.{{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 }} Chalcone isomerase then isomerizes the product to close the pyrone ring to make naringenin. Finally, a flavanone synthase enzyme oxidizes naringenin to apigenin.{{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 }} Two types of flavone synthase (FNS) have been described; FNS I, a soluble enzyme that uses 2-oxogluturate, Fe²⁺, and ascorbate as cofactors and FNS II, a membrane bound, NADPH dependent cytochrome p450 monooxygenase.{{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 }}

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{{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 }} 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:[https://www.ars.usda.gov/ARSUserFiles/80400525/Data/Flav/Flav_R03.pdf USDA Database for the Flavonoid Content of Selected Foods, Release 3 (2011)]

class="wikitable"
Product ! Apigenin (milligrams per 100 grams)
Parsley, dried \| 4503.5
Parsley, fresh \| 215.5
Celery hearts, green \| 19.1
Rutabagas, raw \| 4

class="wikitable"

Product

! Apigenin
(milligrams per 100 grams)

Parsley, dried

| 4503.5

Parsley, fresh

| 215.5

Celery hearts, green

| 19.1

Rutabagas, raw

| 4