Apigenin

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. 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.

Pharmacology

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

Biosynthesis

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

Glycosides

The naturally occurring glycosides formed by the combination of apigenin with sugars include:

• Apiin (apigenin 7-O-apioglucoside), isolated from parsley 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:

References

References

1. ''[[Merck Index]]'', 11th Edition, '''763'''.
2. The Systematic Identification of Flavonoids. Mabry et al, 1970, page 81
3. (August 2015). "Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease". Neural Regeneration Research.
4. (November 2015). "Flavonoids". [[Linus Pauling Institute]], Oregon State University.
5. (June 1995). "Apigenin, a component of ''Matricaria recutita'' flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects". Planta Medica.
6. (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.
7. (2000-06-01). "Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla". Biochemical Pharmacology.
8. Forkmann, G.. (January 1991). "Flavonoids as Flower Pigments: The Formation of the Natural Spectrum and its Extension by Genetic Engineering". Plant Breeding.
9. (January 1995). "The shikimate pathway as an entry to aromatic secondary metabolism". Plant Physiology.
10. (September 2015). "Biosynthesis of Two Flavones, Apigenin and Genkwanin, in Escherichia coli". Journal of Microbiology and Biotechnology.
11. (February 2003). "The chalcone synthase superfamily of type III polyketide synthases". Natural Product Reports.
12. (September 2001). "Cloning of parsley flavone synthase I". Phytochemistry.
13. (December 2005). "Investigation of two distinct flavone synthases for plant-specific flavone biosynthesis in ''Saccharomyces cerevisiae''". Applied and Environmental Microbiology.
14. (2006). "Bioavailability of apigenin from apiin-rich parsley in humans". Annals of Nutrition & Metabolism.
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)]