Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is a

flavone Flavone is an organic compound with the formula . A white solid, flavone is a derivative of chromone with a phenyl (Ph) substituent adjacent to the ether group. The compound is of little direct practical importance, but substituted derivatives, ...

compound that is the

aglycone An aglycone (aglycon or genin) is the chemical compound remaining after the glycosyl group on a glycoside is replaced by a hydrogen atom. For example, the aglycone of a cardiac glycoside would be a steroid A steroid is an organic compoun ...

of several naturally occurring

glycosides In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...

. It is a yellow crystalline solid that has been used to dye wool. Apigenin is abundant in

parsley Parsley, or garden parsley (''Petroselinum crispum''), is a species of flowering plant in the family Apiaceae that is native to Greece, Morocco and the former Yugoslavia. It has been introduced and naturalisation (biology), naturalized in Eur ...

celery Celery (''Apium graveolens'' Dulce Group or ''Apium graveolens'' var. ''dulce'') is a cultivated plant belonging to the species ''Apium graveolens'' in the family Apiaceae that has been used as a vegetable since ancient times. The original wild ...

celeriac Celeriac (''Apium graveolens'' Rapaceum Group, synonyms ''Apium graveolens'' Celeriac Group and ''Apium graveolens'' var. ''rapaceum''), also called celery root, knob celery, and turnip-rooted celery (although it is not a close relative of the ...

, and

chamomile Chamomile (American English) or camomile (British English; see spelling differences) ( or ) is the common name for several plants of the family Asteraceae. Two of the species, '' Matricaria chamomilla'' and '' Chamaemelum nobile'', are commo ...

flowers Flowers, also known as blooms and blossoms, are the reproductive structures of flowering plants ( angiosperms). Typically, they are structured in four circular levels, called whorls, around the end of a stalk. These whorls include: calyx, m ...

. 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,

, and chamomile tea are the most common sources. Apigenin is particularly abundant in the flowers of chamomile plants, constituting 68% of total

flavonoid Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans. Chemically, flavonoids ...

s. 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 Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

site on GABA_A 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 -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

, both products of the

Shikimate pathway The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) ...

. 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 In enzymology, a trans-cinnamate 4-monooxygenase () is an enzyme that catalyzes the chemical reaction :trans-cinnamate + NADPH + H+ + O2 \rightleftharpoons 4-hydroxycinnamate + NADP+ + H2O The 4 substrates of this enzyme are trans-cinnamate, N ...

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 Polyketide synthases (PKSs) are a family of multi- domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share ...

enzyme

chalcone synthase Chalcone synthase or naringenin-chalcone synthase (CHS) is an enzyme ubiquitous to higher plants and belongs to a family of polyketide synthase enzymes (PKS) known as type III PKS. Type III PKSs are associated with the production of chalcones, a ...

uses consecutive condensations of three equivalents of

malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Biosynthesis Malonyl-CoA cannot cross membranes and there is no known malonyl-CoA import mechanism. The biosynthesis therefore takes place locally: * cytosol: Malonyl-CoA is formed by c ...

followed by aromatization to convert ''p''-coumaroyl-CoA to

chalcone Chalcone is the organic compound C6H5C(O)CH=CHC6H5. It is an α,β-unsaturated ketone. A variety of important biological compounds are known collectively as chalcones or chalconoids. They are widely known bioactive substances, fluorescent materi ...

Chalcone isomerase In enzymology, a chalcone isomerase () is an enzyme that catalyzes the chemical reaction :a chalcone \rightleftharpoons a flavanone Hence, this enzyme has one substrate, a chalcone, and one product, a flavanone. This enzyme belongs to the fam ...

then isomerizes the product to close the pyrone ring to make

naringenin Naringenin is a flavanone from the flavonoid group of polyphenols. It is commonly found in citrus fruits, especially as the predominant flavonone in grapefruit. The fate and biological functions of naringenin in vivo are unknown, remaining und ...

. 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 Apiin is a natural flavonoid, a diglycoside of the flavone apigenin found in the winter-hardy plants parsley and celery Celery (''Apium graveolens'' Dulce Group or ''Apium graveolens'' var. ''dulce'') is a cultivated plant belonging to the ...

(apigenin 7-''O''-apioglucoside), isolated from

and celery *

Apigetrin Apigetrin is a chemical compound that can be found in dandelion coffee Dandelion coffee (also dandelion tea) is a herbal tea, tisane made from the root of the Taraxacum, dandelion plant. The roasted dandelion root pieces and the beverage have s ...

(apigenin 7-

glucoside A glucoside is a glycoside that is chemically derived from glucose. Glucosides are common in plants, but rare in animals. Glucose is produced when a glucoside is hydrolysed by purely chemical means, or decomposed by fermentation or enzymes. Th ...

), found in

dandelion coffee Dandelion coffee (also dandelion tea) is a herbal tea, tisane made from the root of the Taraxacum, dandelion plant. The roasted dandelion root pieces and the beverage have some resemblance to coffee in appearance and taste, and it is thus commonly ...

* 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: USDA Database for the Flavonoid Content of Selected Foods, Release 3 (2011)
/ref>

References