A novel 11 beta-hydroxysteroid dehydrogenase inhibitor contained in saiboku-to, a herbal remedy for steroid-dependent bronchial asthma.
To identify the inhibitor of prednisolone metabolism contained in Saiboku-To, we conducted in-vitro experiments of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), using rat liver homogenate and cortisol as a typical substrate. We studied the effects of ten herbal constituents on 11 beta-HSD. Five herbal extracts showed inhibitory activity with Glycyrrhiza glabra > Perillae frutescens > Zizyphus vulgaris > Magnolia officinalis > Scutellaria baicalensis. This suggests that unknown 11 beta-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 x 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 11 beta-HSD.
Homma
M
M
Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
Oka
K
K
Niitsuma
T
T
Itoh
H
H
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001713:Biphenyl Compounds / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003348:Cortisone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000032:analysis; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D006854:Hydrocortisone / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017705:Lignans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020835:Medicine, Kampo; D051381:Rats; D017208:Rats, Wistar; D000498:Allyl Compounds; D010636:Phenols
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D003348:Cortisone; D004365:Drugs, Chinese Herbal; D005938:Glucocorticoids; D006034:Glycyrrhetinic Acid; D019695:Glycyrrhizic Acid; D006854:Hydrocortisone; D006913:Hydroxysteroid Dehydrogenases; D007166:Immunosuppressive Agents; D017705:Lignans; C045086:saiboku-to; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols