植物乳茄（EF）是中国常见的草药，具有悠久的药用历史，已经证明对癌症、心血管疾病和阿尔茨海默病等许多有前途的药理作用。然而，与EF消费相关的肝毒性报告越来越多。不幸的是，从长远来看，EF的许多隐性成分及其毒性机制仍不为人所了解。最近，代谢激活EF的肝毒性化合物生成反应性代谢物（RMs）被认为与此有关。在这里，我们捕获与这些化合物肝毒性相关的代谢反应。首先，EF的肝毒性化合物被肝细胞色素P450酶（CYP450）酶催化氧化，生成RMs。随后，高度亲电的RMs可以与生物分子中包含的亲核基团反应，如肝蛋白、酶和核酸，形成结合物和/或加合物，导致一系列毒理后果。此外，目前提出的生物病理发病机制，包括氧化应激、线粒体损伤和功能障碍、内质网（ER）应激、肝代谢紊乱和细胞凋亡。简而言之，本文更新了代谢激活EF的七种肝毒性化合物路径的知识，并从生化角度提供了对提出的分子肝毒性机制的相关见解，以便为在临床上合理应用EF提供理论指南。

Evodiae Fructus (EF) is a common herbal medicine with thousands of years of medicinal history in China, which has been demonstrated with many promising pharmacological effects on cancer, cardiovascular diseases and Alzheimer's disease. However, there have been increasing reports of hepatotoxicity associated with EF consumption. Unfortunately, in a long term, many implicit constituents of EF as well as their toxic mechanisms remain poorly understood. Recently, metabolic activation of hepatotoxic compounds of EF to generate reactive metabolites (RMs) has been implicated. Herein, we capture metabolic reactions relevant to hepatotoxicity of these compounds. Initially, catalyzed by the hepatic cytochrome P450 enzymes (CYP450s), the hepatotoxic compounds of EF are oxidized to generate RMs. Subsequently, the highly electrophilic RMs could react with nucleophilic groups contained in biomolecules, such as hepatic proteins, enzymes, and nucleic acids to form conjugates and/or adducts, leading to a sequence of toxicological consequences. In addition, currently proposed biological pathogenesis, including oxidative stress, mitochondrial damage and dysfunction, endoplasmic reticulum (ER) stress, hepatic metabolism disorder, and cell apoptosis are represented. In short, this review updates the knowledge on the pathways of metabolic activation of seven hepatotoxic compounds of EF and provides considerable insights into the relevance of proposed molecular hepatotoxicity mechanisms from a biochemical standpoint, for the purpose of providing a theoretical guideline for the rational application of EF in clinics.