Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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11-beta-Hydroxysteroid Dehydrogenases
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Animals
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Antineoplastic Agents, Phytogenic / isolation & purification
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Antineoplastic Agents, Phytogenic / pharmacology
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Antineoplastic Agents, Phytogenic / therapeutic use
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Asthma / drug therapy*
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Biphenyl Compounds / isolation & purification
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Biphenyl Compounds / pharmacology
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Biphenyl Compounds / therapeutic use
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Chromatography, High Pressure Liquid
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Cortisone / biosynthesis
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal / chemistry
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Drugs, Chinese Herbal / pharmacology*
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Drugs, Chinese Herbal / therapeutic use
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Glucocorticoids / analysis
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Glycyrrhetinic Acid / analogs & derivatives
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Glycyrrhetinic Acid / pharmacology
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Glycyrrhizic Acid
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Hydrocortisone / metabolism
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Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / pharmacology*
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Immunosuppressive Agents / therapeutic use
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Lignans*
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Liver / drug effects*
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Liver / enzymology
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Male
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Medicine, Kampo*
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Rats
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Rats, Wistar
Substances
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Antineoplastic Agents, Phytogenic
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Biphenyl Compounds
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Drugs, Chinese Herbal
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Glucocorticoids
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Immunosuppressive Agents
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Lignans
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saiboku-to
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magnolol
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honokiol
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Glycyrrhizic Acid
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Hydroxysteroid Dehydrogenases
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11-beta-Hydroxysteroid Dehydrogenases
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Glycyrrhetinic Acid
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Cortisone
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Hydrocortisone