【摘要】 为探究北柴胡叶提取物（BCLE）抗对乙酰氨基酚（APAP）肝损伤的作用，采用液相-质谱法（LC-MS）、网络药理学、分子对接，并建立小鼠模型研究BCLE治疗效果及抗APAP肝损伤作用机制。网络药理学结果表明，BCLE活性成分有19种，BCLE与DILI公共靶点244个，核心靶点44个，且活性成分与脂酰肌醇3-激酶（PI3K）、蛋白激酶B（AKT）信号通路相关性较高，分子对接显示活性成分与通路之间亦有良好的亲和力。动物试验结果表明，BCLE对APAP肝损伤有良好的治疗效果，可显著降低APAP模型组小鼠血清中谷丙转氨酶（ALT）和谷草转氨酶（AST）活力，缓解肝细胞损伤，减轻N-乙酰基-P-苯醌亚胺（NAPQI）的聚积，升高还原型谷胱甘肽（GSH）含量和超氧化物歧化酶（SOD）活性，降低丙二醛（MDA）和过氧化氢（H₂O₂）含量，并显著上调APAP肝损伤小鼠磷酸化脂酰肌醇3-激酶（p-PI3K）、磷酸化蛋白激酶B（p-AKT）蛋白表达。综上，网络药理学与分子对接预测BCLE通过PI3K-AKT通路作用于APAP肝损伤，体内试验表明，BCLE可通过保护肝细胞，缓解氧化应激，上调PI3K-AKT通路抗APAP肝损伤。研究结果可为进一步提升北柴胡的药用价值，研发抗APAP肝损伤新型药物提供理论思路和试验依据。更多还原

【Abstract】 To investigate the protective effects of Bupleurum chinense leaf extract(BCLE) against acetaminophen(APAP)-induced hepatotoxicity, this study employed liquid chromatography-mass spectrometry(LC-MS), network pharmacology, molecular docking, and murine models to elucidate BCLE’s therapeutic efficacy and underlying mechanism. Network pharmacology analysis identified 19 bioactive compounds in BCLE and revealed 244 shared targets between BCLE and drug-induced liver injury(DILI), with 44 core targets highly enriched in the phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT) signaling pathway. Molecular docking confirmed strong binding affinities between BCLE’s active components and key nodes within the PI3 KAKT pathway. In vivo experiments demonstrated that BCLE significantly attenuated APAP-induced liver injury by reducing serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST), alleviating hepatocellular necrosis, and decreasing hepatic accumulation of the toxic metabolite N-acetyl-p-benzoquinone imine(NAPQI). BCLE treatment also enhanced antioxidant capacity, as evidenced by elevated glutathione(GSH) content and superoxide dismutase(SOD) activity, alongside reduced malondialdehyde(MDA) and hydrogen peroxide(H2O2) levels. Mechanistically, BCLE upregulated the expression of phosphorylated PI3K(p-PI3K) and phosphorylated AKT(p-AKT) in APAP-damaged livers, indicating activation of the PI3K-AKT pathway. Integrated findings suggest that BCLE mitigates APAP hepatotoxicity by modulating oxidative stress, enhancing cellular antioxidant defenses, and activating the PI3K-AKT signaling pathway to promote hepatocyte survival. This study provides critical theoretical and experimental evidence for leveraging Bupleurum chinense in developing novel therapeutics against APAP-induced liver injury.更多还原