【摘 要】
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Panaxytriol (PXT) was one of the active ingredient in red ginseng extractive, and could inhibit the activity of some cancer cell.In our previous study, PXT was shown to differentially affect the metab
【机 构】
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南昌大学临床药理研究所,南昌,330006
【出 处】
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中国药理学会药物临床试验专业委员会首届学术研讨会
论文部分内容阅读
Panaxytriol (PXT) was one of the active ingredient in red ginseng extractive, and could inhibit the activity of some cancer cell.In our previous study, PXT was shown to differentially affect the metabolic pathways ofmidazolam (MDZ), significantly enhance MDZ l-hydroxylation but inhibit MDZ 4-hydroxylation.To assess the effect mechanism of PXT on midazolam (MDZ) l-hydroxylation and 4-hydroxylation mediated by CYP3A4, we investigated the CYP3A enzyme effects of PXT in liver microsome and rat primary hepatocyte.The results presented that PXT was shown to differentially affect CYP3A4-mediated 1-hydroxylation and 4-hydroxylation of MDZ in rat liver microsome (RLM) and human liver microsome (HLM).However, it was found that PXT enhanced the inhibition effect on MDZ 4-hydroxylation and also presented inhibition effect on MDZ l-hydroxylation.Moreover, PXT had inhibition effect on the expression of CYP3A1/2 mRNA through real-time polymerase chain reaction analysis.Overall, these results showed that treatment with PXT decreased the CYP3A enzyme metabolic activity and mRNA levels in a concentration-dependent manner in rat primary hepatocytes.We comprehensively clarified the effect mechanism of PXT on MDZ 4-hydroxylation and l-hydroxylation mediated by CYP3A through three aspects including enzyme kinetics, CYP3A enzyme activity variation and CYP3A1/2mRNA expression level.Our results showed that PXT could inhibit CYP3A and may play an important role in the potential drug metabolic interactions, providing scientific basis for clinical safe and rational use of drugs.
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