【摘要】 目的 研究石菖蒲挥发油（VOA）致肝毒性作用机制，为VOA相关药品安全性的提高提供参考依据。方法 采用气相色谱-质谱联用技术对VOA进行全成分分析。进行急性经口毒性试验及组织病理切片观察VOA毒性作用。并结合网络药理学与分子对接实验探究VOA中致肝毒性成分及其作用机制。结果 GC-MS对VOA进行全成分分析得到103个峰。急性经口毒性试验及肝组织病理切片观察显示VOA有肝毒性作用。网络药理学结果显示，与肝毒性密切相关的富集通路为DNA加合物的化学致癌作用通路、糖尿病并发症中的AGE-RAGE信号通路、细胞色素P450药物代谢信号通路等。分子对接结果显示：β-石竹烯、1,2,4a,5,6,8a-六氢-4,7-二甲基-1-(1-甲基乙基)萘、埃雷莫菲拉酮与潜在毒性靶点具有良好结合效果。结论 VOA中主要肝毒性成分可能是β-石竹烯、1,2,4a,5,6,8a-六氢-4,7-二甲基-1-(1-甲基乙基)萘、埃雷莫菲拉酮，VOA可能通过多成分、多靶点、多通路的方式产生肝毒性。更多还原

【Abstract】 Objective To determine the mechanism of hepatotoxicity caused by volatile oil from Acori tatarinowii(VOA), and improve the safety of VOA-related drugs. Methods VOA was analyzed by gas chromatography-mass spectrometry. Acute oral toxicity test and liver tissue pathological sections were performed to observe the toxic effects of VOA. Network pharmacology and molecular docking experiments were combined to determine the hepatotoxic components in VOA and their hepatotoxic mechanisms. Results GC-MS was used to analyze the whole components of VOA and 103 peaks were obtained. Acute oral toxicity test and liver tissue pathological section observation showed that VOA had hepatotoxic effect. The network pharmacology showed that the enriched pathways closely related to hepatotoxicity included the chemical carcinogenesis pathway of DNA adducts, the AGERAGE signaling pathway in diabetic complications, and the cytochrome P450 drug metabolism signaling pathway. Molecular docking showed that β-caryophyllene, 1, 2, 4a, 5, 6, 8a-hexahydro-4,7-dimethyl-1-(1-methylethyl) naphthalene, eremophila ketone and potential toxic targets had good binding effect. Conclusion The main hepatotoxic components in VOA may be β-caryophyllene, 1, 2,4a, 5, 6, 8a-hexahydro-4, 7-dimethyl-1-(1-methylethyl) naphthalene, and eremophila ketone. VOA may present hepatotoxicity through multi-component, multi-target and multi-channel approaches.更多还原