Apigenin Explained

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

Sources in nature

Apigenin is found in many fruits and vegetables, but parsley, celery, celeriac, and chamomile tea are the most common sources.^[1] Apigenin is particularly abundant in the flowers of chamomile plants, constituting 68% of total flavonoids.^[2] Dried parsley can contain about 45 mg apigenin/gram of the herb, and dried chamomile flower about 3–5 mg/gram.^[3] The apigenin content of fresh parsley is reportedly 215.5 mg/100 grams, which is much higher than the next highest food source, green celery hearts providing 19.1 mg/100 grams.^[4]

Pharmacology

Apigenin competitively binds 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 (PAL) to make cinnamate, followed by oxidation at the para position by cinnamate 4-hydroxylase (C4H) 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 (TAL) to arrive at p-coumarate.^[10] To complete the general phenylpropanoid pathway, 4-coumarate CoA ligase (4CL) substitutes coenzyme A (CoA) at the carboxy group of p-coumarate. Entering the flavone synthesis pathway, the type III polyketide synthase enzyme chalcone synthase (CHS) uses consecutive condensations of three equivalents of malonyl CoA followed by aromatization to convert p-coumaroyl-CoA to chalcone.^[11] Chalcone isomerase (CHI) then isomerizes the product to close the pyrone ring to make naringenin. Finally, a flavanone synthase (FNS) enzyme oxidizes naringenin to apigenin.^[12] Two types of FNS have previously 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:

• 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)
Dried parsley	4500
	300–500
	215.5
Celery hearts, green	19.1
Rutabagas, raw	4

See also

• Amentoflavone

Notes and References

1. http://medicalxpress.com/news/2013-05-compound-mediterranean-diet-cancer-cells.html The compound in the Mediterranean diet that makes cancer cells 'mortal'
2. Venigalla M, Gyengesi E, Münch G . Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease . Neural Regeneration Research . 10 . 8 . 1181–5 . August 2015 . 26487830 . 4590215 . 10.4103/1673-5374.162686 . free .
3. Shankar E, Goel A, Gupta K, Gupta S . Plant flavone apigenin: An emerging anticancer agent . . 3 . 6 . 423–446 . 2017 . 10.1007/s40495-017-0113-2 . 5791748 . 29399439.
4. Web site: Delage, PhD . Barbara . Flavonoids . Linus Pauling Institute, Oregon State University . Corvallis, Oregon. 2021-01-26. November 2015.
5. Viola . H. . Wasowski . C. . Levi de Stein . M. . Wolfman . C. . Silveira . R. . Dajas . F. . Medina . J. H. . Paladini . A. C. . June 1995 . Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects . Planta Medica . 61 . 3 . 213–216 . 10.1055/s-2006-958058 . 0032-0943 . 7617761.
6. Dekermendjian . K. . Kahnberg . P. . Witt . M. R. . Sterner . O. . Nielsen . M. . Liljefors . T. . 1999-10-21 . 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 . 10.1021/jm991010h . 0022-2623 . 10543878.
7. Avallone . R. . Zanoli . P. . Puia . G. . Kleinschnitz . M. . Schreier . P. . Baraldi . M. . 2000-06-01 . Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla . Biochemical Pharmacology . 59 . 11 . 1387–1394 . 10.1016/s0006-2952(00)00264-1 . 0006-2952 . 10751547.
8. Forkmann. G.. January 1991. Flavonoids as Flower Pigments: The Formation of the Natural Spectrum and its Extension by Genetic Engineering. Plant Breeding. en. 106. 1. 1–26. 10.1111/j.1439-0523.1991.tb00474.x. 0179-9541. free.
9. Herrmann KM . The shikimate pathway as an entry to aromatic secondary metabolism . Plant Physiology . 107 . 1 . 7–12 . January 1995 . 7870841 . 161158 . 10.1104/pp.107.1.7 .
10. Lee H, Kim BG, Kim M, Ahn JH . Biosynthesis of Two Flavones, Apigenin and Genkwanin, in Escherichia coli . Journal of Microbiology and Biotechnology . 25 . 9 . 1442–8 . September 2015 . 25975614 . 10.4014/jmb.1503.03011 . free .
11. Austin MB, Noel JP . The chalcone synthase superfamily of type III polyketide synthases . Natural Product Reports . 20 . 1 . 79–110 . February 2003 . 12636085 . 10.1039/b100917f . 10.1.1.131.8158 .
12. Martens S, Forkmann G, Matern U, Lukacin R . Cloning of parsley flavone synthase I . Phytochemistry . 58 . 1 . 43–6 . September 2001 . 11524111 . 10.1016/S0031-9422(01)00191-1 .
13. Leonard E, Yan Y, Lim KH, Koffas MA . Investigation of two distinct flavone synthases for plant-specific flavone biosynthesis in Saccharomyces cerevisiae . Applied and Environmental Microbiology . 71 . 12 . 8241–8 . December 2005 . 16332809 . 1317445 . 10.1128/AEM.71.12.8241-8248.2005 . 2005ApEnM..71.8241L .
14. Meyer H, Bolarinwa A, Wolfram G, Linseisen J . Bioavailability of apigenin from apiin-rich parsley in humans . Annals of Nutrition & Metabolism . 50 . 3 . 167–72 . 2006 . 16407641 . 10.1159/000090736 . 8223136 .
15. https://www.ars.usda.gov/ARSUserFiles/80400525/Data/Flav/Flav_R03.pdf USDA Database for the Flavonoid Content of Selected Foods, Release 3 (2011)