吴茱萸有小毒，《中国药典》规定用甘草炮制。一些研究表明吴茱萸致肝毒性与相关蛋白表达有关，但目前的努力缺乏毒性物质体内、外代谢过程的支撑，且甘草制吴茱萸减毒机理不明。我们研究表明，甘草炮制吴茱萸肝毒性明显降低，吴茱萸主要生物碱类在大鼠体内生物利用度明显增加，推测吴茱萸肝毒性与体内代谢物密切相关。同时，甘草中有诱导II 相代谢酶的成分。因此，我们首次提出基于“CYP 450-UGT”双重模式的吴茱萸致肝毒性和甘草炮制减毒的物质基础和机理研究：1. 从整体动物层面研究吴茱萸在大鼠体内代谢活化对肝毒性及药动学的影响；从细胞层面监测GSH水平-吴茱萸浓度-肝毒性的相关性；2. 鉴定吴茱萸的代谢物和相关的酶；3. 考察甘草抑制P450酶和诱导UGT的代谢过程。本课题融合药物代谢学、毒理化学和分子生物学等技术，为同类中药炮制减毒研究提供模式和借鉴，阐明炮制减毒机理是中药合理使用亟待解决的科学问题。

Evodiae Fructus (EF), having slight toxicity, needs to be processed with licorice juice, which is recorded in the Chinese pharmacopoeia. Some research showed that hepatotoxicity resulted from EF was connected with associated protein expression. But present attempts lack metabolic process of poisonous substance in vivo and in vitro. And there is little study on the mechanism of toxicity attenuated by Evodiae Fructus processed (EFP) with licorice juice. Recently, our studies showed that hepatotoxicity of EFP was remarkably decreased, while bioavailability of main alkaloids from EFP had significant increase compared with those from EF. We speculated that toxicity of EF could be related to its metabolites in vivo. Meanwhile, there are constituents inducing activities of UGTs in licorice. So we first proposed the idea of studies on material basis and mechanism-based “CYP450-UGT” hepatotoxicity resulted from EF and toxicity attenuated by EFP: 1. research the effect of hepatotoxicity and pharmacokinetic resulted from metabolism activation of EF in rats ; monitor the relationship of the levels of GSH, concentration of EF and hepatotoxicity in cellular level; 2. identify the metabolites of EF and the related enzymes；3. investigate the processes of inhibiting CYP450s and inducing UGTs of licorice. We will employ various technologies and methods such as drug metabolism, toxicology chemistry and molecular biology technologies. The study will provide strongly scientific evidence and reference for the study of toxicity attenuation of the same processing of TCM. Clarifying mechanism of toxicity attenuated by Chinese crude drug processing is the scientific problem of the fair use of TCM, which needs to be solved promptly.