淫羊藿Epimedii Folium作为常用补肾中药，广泛应用于骨关节疾病及肾虚相关病证治疗，其相关肝毒性问题近年来逐渐受到关注。现有研究表明，淫羊藿相关肝损伤并非典型剂量相关性毒性，而更具特发性特征，其发生与成分特性、配伍模式及宿主易感性密切相关。机制研究显示，淫羊藿次苷I、淫羊藿次苷II及宝藿苷I等为潜在核心毒性成分，主要通过激活NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎症小体、诱导氧化应激及干扰胆汁酸稳态等途径介导肝脏的受损反应。在配伍方面，与补骨脂联用可在免疫应激背景下协同激活丝裂原活化蛋白激酶（MAPK）信号通路并引发脂质代谢紊乱，从而放大毒性效应；与何首乌联用则可能通过炎症反应与代谢酶抑制的交互作用促进毒性成分蓄积。宿主因素亦在其中发挥关键作用，炎症状态及轻度免疫应激可通过抑制药物代谢酶活性并增强免疫反应，显著降低机体对外源性成分的耐受阈值。总体而言，淫羊藿相关肝毒性本质上是免疫激活与代谢失衡相互作用的结果。有待进一步加强多组学数据整合与机制研究，以促进其风险评估由经验判断向精准预测转变，从而提高临床用药安全性。

Epimedii Folium, a commonly used traditional Chinese medicine for tonifying the kidneys, is widely employed in the treatment of musculoskeletal disorders and conditions associated with kidney deficiency; however, concerns regarding its potential hepatotoxicity have gradually come to the fore in recent years. Existing research indicates that Epimedii Folium-related liver damage is not a typical dose-dependent toxicity, but rather exhibits idiopathic characteristics, with its occurrence being closely linked to the properties of its constituents, formulation patterns, and host susceptibility. Mechanistic studies suggest that epimedin I, epimedin II, and baohuoside I are potential core toxic components, which may induce liver injury through activation of the NLRP3 inflammasome, oxidative stress, and disruption of bile acid homeostasis. In terms of compatibility, co-administration with Psoraleae Fructus under immune stress conditions can synergistically activate MAPK signaling and induce lipid metabolic disturbances, thereby amplifying hepatotoxicity. Co-administration with Polygoni Multiflori Radix may enhance toxic effects through the interaction between inflammatory responses and inhibition of drug-metabolizing enzymes, leading to the accumulation of toxic constituents. Host factors also play a critical role, as inflammatory states and mild immune stress can suppress drug-metabolizing enzyme activity and enhance immune responses, thereby lowering the tolerance threshold to xenobiotics. Overall, Epimedii Folium-associated hepatotoxicity is driven by the interplay between immune activation and metabolic dysregulation. Future studies integrating multi-omics data and mechanistic modeling are warranted to facilitate the transition from empirical risk assessment to precision prediction, ultimately improving clinical safety.

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