title: Bimodal action of miroestrol and deoxymiroestrol, phytoestrogens from Pueraria candollei var. mirifica, on hepatic CYP2B9 and CYP1A2 expressions and antilipid peroxidation in mice.
abstract: Miroestrol and deoxymiroestrol are phytoestrogens isolated from Pueraria candollei var. mirifica. The influence of miroestrol and dexoymirosestrol on hepatic cytochrome P450 (P450) enzymes and antioxidative activity in brain was examined in C57BL/6 mice compared with that of a synthetic female sex hormone estradiol. We hypothesized that miroestrol and deoxymiroestrol would induce CYP2B9 expression, whereas CYP1A2 expression would be suppressed compared with estradiol. Miroestrol and deoxymiroestrol treatment significantly increased uterus weight and volume. In addition, both of these phytoestrogens induced the expression of CYP2B9 and suppressed the expression of CYP1A2, as expected. Hepatic P450 activities correspondingly showed that both compounds increased benzyloxyresorufin O-dealkylase activity, whereas methoxyresorufin O-dealkylase activity was reduced. These observations suggested that miroestrol and deoxymiroestrol might affect hepatic P450 enzymes, including the CYP2B9 and CYP1A2 P450 isoforms. Assessment of lipid peroxidation demonstrated that miroestrol and deoxymiroestrol markedly decreased levels of malondialdehyde formation in the mouse brain. This is the first report suggesting miroestrol and deoxymiroestrol as potential alternative medicines to estradiol because of their distinctive ability to regulate mouse hepatic P450 expression and their beneficial antioxidative activities.
authors.affiliation: Academic Office for Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Latiporn
authors.initials: L
authors.lastname: Udomsuk
authors.forename: Thaweesak
authors.initials: T
authors.lastname: Juengwatanatrakul
authors.forename: Waraporn
authors.initials: W
authors.lastname: Putalun
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Jarukamjorn
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004958:Estradiol / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D048789:Phytoestrogens / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D029908:Pueraria / Q000737:chemistry*; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D003374:Coumarins; D005227:Fatty Acids; D048789:Phytoestrogens; D010936:Plant Extracts; D013256:Steroids; C406602:deoxymiroestrol; C013584:lipid peroxidation inhibitor; C571572:miroestrol; D004958:Estradiol; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C121503:Cyp2b9 protein, mouse; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1; D000072467:Cytochrome P450 Family 2