Taxifolin is a rat and human 11β-hydroxysteroid dehydrogenase 1 inhibitor as a possible drug to treat the metabolic syndrome

Abstract

11β-Hydroxysteroid dehydrogenase 1 (HSD11B1) is an NADPH-dependent oxidoreductase that elevates cortisol (in human beings) or corticosterone (in rats) locally via metabolically activating 11 keto-glucocorticoids. Taxifolin is a flavonoid in food plants. The present study investigated the effects of taxifolin on rat and human liver microsomal HSD11B1. Taxifolin competitively inhibited rat and human HSD11B1 against steroid cortisone or 11-dehydrocorticosterone, with IC50 values of 37,833 and 4981 nM, respectively. Oral administration of 5 and 10 mg/kg taxifolin for 30 min significantly inhibited rat liver HSD11B1 ex vivo and suppressed cortisone metabolism as shown by the significant increase of T1/2, Cmax, Tmax, and the area under curve (AUC) after exogenous injection of cortisone in vivo. This result shows that taxifolin is a potent inhibitor of both rat and human HSD11B1, being a possible supplement to treat the metabolic syndrome.