Apigenine; Chamomile; Apigenol; Spigenin; Versulin; 4′,5,7-Trihydroxyflavone; C.I. Natural Yellow 1
3D model (JSmol)
|Molar mass||270.24 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|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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.
In in vitro experiments and animal studies, a variety of potential biological activities of apigenin have been identified.
Apigenin induces autophagy (a kind of cellular waste-recycling system) in leukemia cells, which may support a possible chemopreventive role. Induced autophagy interferes with the action of the chemotherapy drug vincristine. Apigenin is a potent inhibitor of CYP2C9, an enzyme responsible for the metabolism of many pharmaceutical drugs in the body. Apigenin dimers can reverse the highest level of drug resistance found in cancer stem cells.
Apigenin has been shown to prevent renal damage caused by ciclosporin in rats, associated with reduced expression of the cell death mediator bcl-2 in histopathological sections. Ciclosporin enhances the expression of transforming growth factor-β in the rat kidney, which signifies accelerated apoptosis. Therefore, transforming growth factor-β and apoptotic index may be used to assess apigenin and its effect on ciclosporin-induced renal damage.
Apigenin acts as a monoamine transporter activator, one of the few chemicals demonstrated to possess this property. Apigenin is a weak ligand for central benzodiazepine receptors in vitro and exerts anxiolytic and slight sedative effects in an animal model. Apigenin shows second-order positive modulatory activity at GABAA receptors. It has also effects on adenosine receptors and is an acute antagonist at the NMDA receptors (IC50 = 10 μM). In addition, like various other flavonoids, apigenin has been found to possess nanomolar affinity for the opioid receptors (Ke = 410 nM, 970 nM, and 410 nM for the μ-, δ-, and κ-opioid receptors, respectively), acting as a non-selective antagonist of all three opioid receptors. Apigenin and its derivatives inhibit fatty acid amide hydrolase at micromolar concentrations, inhibit COX-2 and activate PPAR-γ, suggesting it could have a pharmacological effect on the endocannabinoid system.
In vitro studies have shown that apigenin may be toxic to red blood cells.
Potential health benefits
Apigenin may also stimulate adult neurogenesis, with at least one study claiming that apigenin "stimulate[s] adult neurogenesis in vivo and in vitro, by promoting neuronal differentiation" and may be useful "for stimulating adult neurogenesis and for the treatment of neurological diseases, disorders and injuries, by stimulating the generation of neuronal cells in the adult brain." While potentially promising, the study used rats and its effects have yet to be demonstrated in humans.
Apigenin readily crosses the blood-brain barrier and has not demonstrated toxicity at high doses. It could thus prevent amyloid beta deposition and tau phosphorylation due to neuroinflammation, which are associated with Alzheimer's disease.
Through effects on cell signaling, inflammation, cell cycle, and protease production, apigenin has demonstrated effectiveness against a wide range of cancer types, while not showing toxicity to normal cells. Apigenin is able to block the phosphorylation of certain proteins in pathways that, in the case of a cancer, are over expressed like NF-κB, PI3K, etc... These pathways can induce proliferation, migration and invasion if not regulated.
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.
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 (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. 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. 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. 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.
The naturally occurring glycosides formed by the combination of apigenin with sugars include:
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