吳茱萸是中醫(yī)古籍及現(xiàn)代藥典中記載的傳統(tǒng)中藥材之一，有小毒，歸肝、脾、胃、腎經(jīng)，具有散寒止痛、降逆止嘔、助陽止瀉功效，臨床應(yīng)用廣泛，但因其近年來引發(fā)的肝臟毒性而受到廣泛關(guān)注。經(jīng)研究發(fā)現(xiàn)不同基原的吳茱萸所含的肝毒性成分有所差別，其肝毒性主要由吳茱萸堿、吳茱萸次堿和去氫吳茱萸堿等生物堿和揮發(fā)油引起，其肝毒性機(jī)制繁多而復(fù)雜，主要與過氧化損傷、炎癥反應(yīng)、線粒體損傷、細(xì)胞凋亡、膽汁淤滯、蛋白加合物的形成、細(xì)胞色素P450酶系代謝等機(jī)制異常有關(guān)，實(shí)際應(yīng)用通過配伍和炮制達(dá)到增效減毒的效果。網(wǎng)絡(luò)毒理學(xué)、高內(nèi)涵篩選技術(shù)、定量構(gòu)效關(guān)系（QSAR）毒性預(yù)測、多組學(xué)分析、類器官技術(shù)和人工智能（AI）等新技術(shù)的應(yīng)用有助于深入理解吳茱萸致肝毒性的潛在毒性成分、機(jī)制和減毒原理，并為其臨床安全使用提供科學(xué)依據(jù)。

Euodiae Fructus is one of traditional Chinese medicinal materials recorded in ancient Chinese medicine books and modern pharmacopoeia, with small poison, belonging to the liver, spleen, stomach and kidney meridians, with the effects of dissipating cold and relieving pain, reducing inversion and relieving nausea, helping yang and stopping diarrhea, and is widely used in clinical practice, but it has received extensive attention because of its liver toxicity caused in recent years. The hepatotoxicity is mainly caused by alkaloids and volatile oils such as evodiamine, evodiamine and dehydroevodiamine, and its hepatotoxicity mechanisms are numerous and complex, mainly related to peroxidative damage, inflammatory reaction, mitochondrial damage, apoptosis, cholestasis, protein adduct formation, cytochrome P450 enzyme metabolism and other abnormal mechanisms. The application of new technologies such as network toxicology, high-content screening technology, quantitative structure-activity relationship (QSAR) toxicity prediction, multi-omics analysis, organoid technology and artificial intelligence (AI) is helpful to deeply understand the potential toxic components, mechanisms and attenuation principles of Euodiae Fructus, and provide a scientific basis for its safe clinical use.

R992

國家自然科學(xué)基金資助項(xiàng)目（82204760）