基于网络药理学与分子对接探究北柴胡叶提取物抗APAP肝损伤作用OA

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 PI3K-AKT 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.