Bimodal action of Miroestrol and Deoxymiroestrol, Phytoestrogens from Pueraria Candollei var. Mirifica, on Hepatic CYP2B9 and CYP1A2 Expressions and Antilipid Peroxidation in Mice

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.

Phytochemicals found in herbal medicines have been reported to possess several pharmacologic activities. Extensive studies have been performed to explore their potential for treatment or prevention of disease. Phytoestrogens recently gained much attention after reports that women on a diet rich in phytoestrogens had low incidences of estrogen related cancers, cardiovascular diseases, and climacteric symptoms.

In conclusion, miroestrol and deoxymiroestrol significantly up-regulated CYP2B9 while suppressing CYP1A2 at both transcriptional and enzymatic levels. Miroestrol and deoxymiroestrol also possessed antioxidative activities. These findings revealed miroestrol and deoxymiroestrol as chemopreventive phytoestrogen candidates. However, the modulation of drug-metabolizing enzymes by miroestrol and deoxymiroestrol is important in terms of human health. These enzymes are involved in the metabolism of therapeutic drugs and carcinogens, leading to lowered therapeutic levels or increased adverse effects of those compounds. Therefore, some risk-benefit concerns might be associated with the use of these compounds.

Latiporn Udomsuk, Thaweesak Juengwatanatrakul, Waraporn Putalun and Kanokwan Jarukamjorn,
Academic Office for Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), National Research University-Khon Kaen University, Khon Kaen 40002, Thailand
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand

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