3-methylquercetin and acacetin

Flavonoids are natural compounds that have been extensively studied due to their positive effects on human health. There are over 4000 flavonoids found in higher plants and their beneficial effects have been shown in vitro as well as in vivo. However, data on their pharmacokinetics and influence on metabolic enzymes is scarce. The aim of this study was to focus on possible interactions between the 30 most commonly encountered flavonoid aglycones on the metabolic activity of CYP3A4 enzyme. 6β-hydroxylation of testosterone was used as marker reaction of CYP3A4 activity. Generated product was determined by HPLC coupled with diode array detector. Metabolism and time dependence, as well as direct inhibition, were tested to determine if inhibition was reversible and/or irreversible. Out of the 30 flavonoids tested, 7 significantly inhibited CYP3A4, most prominent being acacetin that inhibited 95% of enzyme activity at 1 µM concentration. Apigenin showed reversible inhibition, acacetin, and chrysin showed combined irreversible and reversible inhibition while chrysin dimethylether, isorhamnetin, pinocembrin, and tangeretin showed pure irreversible inhibition. These results alert on possible flavonoid⁻drug interactions on the level of CYP3A4.

Topics: Apigenin; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Flavanones; Flavones; Flavonoids; Humans; Quercetin; Testosterone

Topics: Antioxidants; Benzaldehydes; Brazil; Chromatography, High Pressure Liquid; Color; Flavanones; Flavones; Flavonoids; Gallic Acid; Hydroxybenzoates; Phenols; Phenylpropionates; Propolis; Quercetin; Tandem Mass Spectrometry; Vanillic Acid

To investigate the chemical constituents of the flowers of Chrysanthemum indicum.. The chemical constituents were isolated by various column chromatographic methods. The structures were identified by spectral data.. Twelve compounds were isolated and identified as acacetin (1), tricin (2), 2',4'-dihydroxychalcone(3), 5-hydroxy-4',7-dimethoxyflavon(4),7hydroxyflavonone (5), isorhamnetin (6),5,6,7-trihydroxy- 3',4', 5'-trimethoxyflanon (7 ), quercetin (8) , (3 beta, 5 alpha, 6 beta, 7 beta, 14 beta)-eudesmen-3,5,6,11-tetrol (9), syringaresinol (10), liriodendrin (11), and genkwanin (12).. Compounds 3-7, 10-12 were isolated from this species for the first time, and compounds 3, 5, 7, 10, 11 were obtained from genus Chrysanthemum for the first time.

Topics: Chalcones; Chrysanthemum; Flavones; Flavonoids; Flavonols; Flowers; Furans; Glucosides; Lignans; Quercetin