Cytotoxicity evaluation and metabolism of hepatotoxicity components of Euodiae Fructus in L02 cells.
Cytotoxicity evaluation and metabolism of hepatotoxicity components of Euodiae Fructus in L02 cells.
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吴茱萸肝毒性成分在L02细胞中的细胞毒性评价及代谢。
DOI：
10.1016/j.jchromb.2021.123040
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Liu Xiaoqiu
中科院分区：
文献类型：
--
作者：
Zhang Wei;Ren Kun;Wu Shuangfeng;Guo Jingyan;Ren Shumeng;Pan Yingni;Wang Dongmei;Morikawa Toshio;Hua Huiming;Liu Xiaoqiu
吴茱萸（Euodiae Fructus，EF）为杜仲（Euodia rutaecarpa（Juss.）本特，据报道显示出抗高血压、抗肿瘤和抗肥胖的作用。EF的主要生物碱被报告为EF毒性的原因，主要通过CYP 3A代谢活化。到目前为止，EF的细胞毒性机制尚未完全阐明。本文研究了CYP 3A诱导剂和抑制剂对EF细胞毒性的影响，以及与EF毒性有关的5种生物碱在L02细胞中的代谢。结果表明，CYP 3A诱导剂可加重毒性，而CYP 3A抑制剂可减轻毒性。采用UPLC-Q-Exactive-MS对L02细胞中的5种生物碱进行了鉴定。在L02细胞中共检测到13种代谢产物。5种生物碱在L02细胞中主要通过氧化、去甲基、脱氢等代谢途径进行代谢，其中氧化代谢是主要代谢途径。推测EF的毒性与CYP 3A密切相关，代谢中间产物可能是EF毒性的原因之一。因此，选择最佳剂量可能是关键，以避免由于EF和CYP 3A诱导剂联合使用的不良反应。
Euodiae Fructus (EF), the dried unripe scented fruit of Euodia rutaecarpa (Juss.) Benth., was reported to show anti-hypertensive, antitumor, and anti-obesity effects. The main alkaloids of EF were reported as the reason for toxicity of EF by metabolic activation majority through CYP3A. Up till the present moment, the cytotoxicity mechanisms of EF have not yet to be fully clarified. For the purposes of this article, the influence of CYP3A inducer and inhibitor on cytotoxicity of EF and metabolism in L02 cells of five alkaloids related to toxicity of EF were evaluated. The results indicated that CYP3A inducer aggravated the toxicity and CYP3A inhibitor alleviated the toxicity. UPLC-Q-Exactive-MS was used for the identification of five alkaloids of EF in L02 cells. A total of 13.metabolites were detected in L02 cells. In general, five alkaloids were widely metabolized in L02 cells such as oxygenation, demethylation, dehydrogenation, and etc. In addition, oxygenation was the main metabolic pathway. It was inferred that the toxicity of EF was closely related to the CYP3A and the metabolic intermediate might be one of the reasons for the toxicity of EF. Hence, the choice of optimal dose might be critical to avoid the adverse reactions owing to combination of EF and CYP3A inducer.
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影响因子：
5.1
作者：
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影响因子：
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作者：
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