【摘 要】
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Aim of the study The hepatotoxicity of Radix Polygoni Multiflori (RPM) has received increasing attention over the past few decades, although the hepatotoxicity mechanism of RPM remained uncertain.The
【机 构】
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State Key Laboratory of Natural Medicines China Pharmaceutical University, No.24 Tong jia Lane, Nanj
【出 处】
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第十届全国药物和化学异物代谢学术会议暨第三届国际ISSX/CSSX联合学术会议
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Aim of the study The hepatotoxicity of Radix Polygoni Multiflori (RPM) has received increasing attention over the past few decades, although the hepatotoxicity mechanism of RPM remained uncertain.The integrated effects, including toxic effects, were the outcome of all components in the herbal medicine.Nevertheless, few studies focused on the multi-component interactions in one herb to elucidate its pharmacological and/or toxic effects.In this study, we intended to show the interaction of constituents contained in RPM, and evaluate the hepatotoxicity mechanism of RPM from the angle of multi-component interactions.Methods The extraction of RPM was divided into stilbene glucosides fraction and emodin fraction, and a rapid high-performance liquid chromatography-mass spectrometry method was developed and validated to show the influence ofstilbene glucosides on pharmac okinetics ofemodin in rats.Liquid-liquid extraction was employed as sample preparation technique.Drug and Statistics 2.0 was used for the estimation of pharmacokinetic parameters.Results The analytical method appeared to be suitable for the analysis of emodin with desirable linearity, accuracy, precision and stability, and the total analysis time was less than 2 min on a short column.Glucuronide ofemodin, the major metabolite of emodin, was further determined after β-glucuronidase hydrolyzation.As the in vivo pharmacokinetic studies indicated, the AUC, Cmax and T1/2 of emodin were relatively increased after the treatment of stilbene glucosides, and glucuronidation of emodin was significantly inhibited.Conclusion This pharmacokinetic interaction might be attributed to the regulation of UDP-glucuronosyltranfferases, and could cause metabolic disorders ofemodin, which would probably lead to the hepatotoxicity of RPM.
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