Suppression of constitutive and inducible cytochrome P450 gene expression by alpha-hederin in mice.
The effects of alpha-Hederin, a triterpenoid saponin which exists in some oriental herbs, on the expression of liver cytochrome P450s were examined in mice. The administration of alpha-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. alpha-Hederin also decreased inducible monooxygenase activities in the same manner. Suppressions of P450 isozyme expression occurred in alpha-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 alpha-Hederin as shown by Northern blot analysis. In contrast, the level of P4502E1 mRNA in the liver of alpha-Hederin treated mice was unchanged. These results suggest that alpha-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.
Jeong
H G
HG
Department of Biological Science, Chosun University, Kwangju, South Korea.
D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D010088:Oxidoreductases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D020033:Protein Isoforms; D011725:Pyridines; D012503:Saponins; C010177:beta-hederin; D008748:Methylcholanthrene; D009828:Oleanolic Acid; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D000815:Aniline Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; C023666:pyridine; D010634:Phenobarbital