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Suppression of constitutive and inducible cytochrome P450 gene expression by α‐hederin in mice

The effects of α‐Hederin, a triterpenoid saponin which exists in some oriental herbs, on the expression of liver cytochrome P450s were examined in mice. The administration of α‐Hederin to mice significantly decreased the hepatic content of P450 and the activities of microsomal ethoxyresorufin O‐deethylase, methoxyresorufin O‐demethylase, and aniline hydroxylase, representative activities of cytochrome‐P4501A1, ‐P4501A2, and ‐P4502E1, respectively, in a dose‐ and time‐dependent manner. However, pentoxyresorufin O‐dealkylase, a representative activity of cytochrome P4502B1/2, was decreased to a lesser extent, α‐Hederin also decreased inducible monooxygenase activities in the same manner. Suppressions of P450 isozyme expression occurred in α‐Hederin treated hepatic microsomes, as determined by immunoblot analysis in a manner consistent with that of the enzyme activity levels. Levels of mRNA of P4501A1/2 and P4502B1/2 were also decreased by α‐Hederin as shown by Northern blot analysis. In contrast, the level of P4502E1 mRNA in the liver of α‐Hederin treated mice was unchanged. These results suggest that α‐Hederin may act as a more specific suppressor for P4501A and P4502E1 than P4502B and that the suppression involves decreases in mRNA levels except in the case of P4502E1.