Apigenin

Apigenin ^[1]

Apigenin
Names
IUPAC name 4′,5,7-Trihydroxyflavone
Systematic IUPAC name 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one
Other names Apigenine; Chamomile; Apigenol; Spigenin; Versulin; C.I. Natural Yellow 1
Identifiers
CAS Number	520-36-5  Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:18388  Y
ChEMBL	ChEMBL28  Y
ChemSpider	4444100  Y
DrugBank	DB07352  Y
ECHA InfoCard	100.007.540
EC Number	208-292-3
IUPHAR/BPS	4136
KEGG	C01477  Y
PubChem CID	5280443
UNII	7V515PI7F6  Y
CompTox Dashboard (EPA)	DTXSID6022391
InChI InChI=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 Y Key: KZNIFHPLKGYRTM-UHFFFAOYSA-N Y 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 Key: KZNIFHPLKGYRTM-UHFFFAOYAX
SMILES O=C\1c3c(O/C(=C/1)c2ccc(O)cc2)cc(O)cc3O
Properties
Chemical formula	C15H10O5
Molar mass	270.240 g·mol−1
Appearance	Yellow crystalline solid
Melting point	345 to 350 °C (653 to 662 °F; 618 to 623 K)
UV-vis (λmax)	267, 296sh, 336 nm in methanol [2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y  verify  (what is  YN ?) Infobox references

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. ^[3] 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. ^[4]

Pharmacology

In vitro , apigenin binds competitively to the benzodiazepine site on GABA_A receptors. ^[5] There exist conflicting findings regarding how apigenin interacts with this site. ^{[6] [7]}

Biosynthesis

Apigenin is biosynthetically derived from the general phenylpropanoid pathway and the flavone synthesis pathway. ^[8] The phenylpropanoid pathway starts from the aromatic amino acids L-phenylalanine or L-tyrosine, both products of the Shikimate pathway. ^[9] 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. ^[10] 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. ^[11] Chalcone isomerase then isomerizes the product to close the pyrone ring to make naringenin. Finally, a flavanone synthase enzyme oxidizes naringenin to apigenin. ^[12] 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. ^[13]

Glycosides

The naturally occurring glycosides formed by the combination of apigenin with sugars include:^{[ citation needed ]}

• Apiin (apigenin 7-O-apioglucoside), isolated from parsley ^[14] 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: ^[15]

Product	Apigenin (milligrams per 100 grams)
Parsley, dried	4503.5
Parsley, fresh	215.5
Celery hearts, green	19.1
Rutabagas, raw	4

See also

• Amentoflavone

References

1. Merck Index , 11th Edition, 763.
2. The Systematic Identification of Flavonoids. Mabry et al, 1970, page 81
3. Venigalla M, Gyengesi E, Münch G (August 2015). "Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease". Neural Regeneration Research. 10 (8): 1181–5. doi: 10.4103/1673-5374.162686 . PMC   4590215 . PMID   26487830.
4. "Flavonoids". Linus Pauling Institute, Oregon State University. November 2015. Retrieved 26 January 2021.
5. Viola H, Wasowski C, Levi de Stein M, et al. (June 1995). "Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects". Planta Medica. 61 (3): 213–216. Bibcode:1995PlMed..61..213V. doi:10.1055/s-2006-958058. ISSN   0032-0943. PMID   7617761.
6. Dekermendjian K, Kahnberg P, Witt MR, et al. (21 October 1999). "Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex". Journal of Medicinal Chemistry. 42 (21): 4343–4350. doi:10.1021/jm991010h. ISSN   0022-2623. PMID   10543878.
7. Avallone R, Zanoli P, Puia G, et al. (1 June 2000). "Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla". Biochemical Pharmacology. 59 (11): 1387–1394. doi:10.1016/s0006-2952(00)00264-1. hdl: 11380/1207274 . ISSN   0006-2952. PMID   10751547.
8. Forkmann G (January 1991). "Flavonoids as Flower Pigments: The Formation of the Natural Spectrum and its Extension by Genetic Engineering". Plant Breeding. 106 (1): 1–26. Bibcode:1991PBree.106....1F. doi: 10.1111/j.1439-0523.1991.tb00474.x . ISSN   0179-9541.
9. Herrmann KM (January 1995). "The shikimate pathway as an entry to aromatic secondary metabolism". Plant Physiology. 107 (1): 7–12. doi:10.1104/pp.107.1.7. PMC   161158 . PMID   7870841.
10. Lee H, Kim BG, Kim M, et al. (September 2015). "Biosynthesis of Two Flavones, Apigenin and Genkwanin, in Escherichia coli". Journal of Microbiology and Biotechnology. 25 (9): 1442–8. doi: 10.4014/jmb.1503.03011 . PMID   25975614.
11. Austin MB, Noel JP (February 2003). "The chalcone synthase superfamily of type III polyketide synthases". Natural Product Reports. 20 (1): 79–110. CiteSeerX   10.1.1.131.8158 . doi:10.1039/b100917f. PMID   12636085.
12. Martens S, Forkmann G, Matern U, et al. (September 2001). "Cloning of parsley flavone synthase I". Phytochemistry. 58 (1): 43–6. Bibcode:2001PChem..58...43M. doi:10.1016/S0031-9422(01)00191-1. PMID   11524111.
13. Leonard E, Yan Y, Lim KH, et al. (December 2005). "Investigation of two distinct flavone synthases for plant-specific flavone biosynthesis in Saccharomyces cerevisiae". Applied and Environmental Microbiology. 71 (12): 8241–8. Bibcode:2005ApEnM..71.8241L. doi:10.1128/AEM.71.12.8241-8248.2005. PMC   1317445 . PMID   16332809.
14. Meyer H, Bolarinwa A, Wolfram G, et al. (2006). "Bioavailability of apigenin from apiin-rich parsley in humans" . Annals of Nutrition & Metabolism. 50 (3): 167–72. doi:10.1159/000090736. PMID   16407641. S2CID   8223136.
15. USDA Database for the Flavonoid Content of Selected Foods, Release 3 (2011)