A Novel 11β-Hydroxysteroid Dehydrogenase Inhibitor Contained in Saiboku-To, a Herbal Remedy for Steroid-dependent Bronchial Asthma

Abstract To identify the inhibitor of prednisolone metabolism contained in Saiboku-To, we conducted in-vitro experiments of 11β-hydroxysteroid dehydrogenase (11β-HSD), using rat liver homogenate and Cortisol as a typical substrate. We studied the effects often herbal constituents on 11β-HSD. Five herbal extracts showed inhibitory activity with Glycyrrhiza glabra > Perillae frutescens< Zizyphus vulgaris > Magnolia officinalis > Scutellaria baicalensis. This suggests that unknown 11β-HSD inhibitors are contained in four herbs other than G. glabra which contains a known inhibitor, glycyrrhizin (and glycyrrhetinic acid). Seven chemical constituents which have been identified as the major urinary products of Saiboku-To in healthy and asthmatic subjects were studied; magnolol derived from M. officinalis showed the most potent inhibition of the enzyme (IC50, 1·8 × 10−4 m). Although this activity was less than that of glycyrrhizin, the inhibition mechanism (non-competitive) was different from a known competitive mechanism. These results suggest that magnolol might contribute to the inhibitory effects of Saiboku-To on prednisolone metabolism through inhibition of 11β-HSD.