The mechanism of Abrus cantoniensis against cholestasis based on metabolomics and network pharmacology

PENG Yingzhen; SUN Hui; ZHAO Jingyu; ZHOU Qian; WU Fangfang; ZHANG Ning

doi:10.13506/j.cnki.jpr.2026.01.002

Abstract：Objective To explore the therapeutic effect and underlying mechanism of Abrus cantoniensis ethanol extract on ANIT-induced cholestasis mouse model based on pharmacodynamics,metabolomics and network pharmacology.Methods Twenty-four male C57BL/6J mice were randomly divided into three groups:normal group(Con),model group(Mod)and Abrus cantoniensis group(AC),the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase acid(ALP),total bilirubin(TBIL)and total bile acid(TBA)in serum of mice were determined by automatic biochemical analyzer;The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the liver tissues of mice were detected by ELISA,Hematoxylin and eosin(HE)staining was used to observe the pathological sections of liver tissue in mice.Untargeted metabolomics was used to detect the differential metabolites in the liver of each group of mice,and network pharmacology was used to predict the potential targets and pathways of Abrus cantoniensis against cholestasis.Results Compared with Con group,the levels of serum AST,ALT,ALP,TBIL and TBA in Mod group were significantly increased(P＜0.05,0.01,0.001),and the levels of TNF-α and IL-6 in liver tissue were increased(P＜0.01);HE staining showed that the connective tissue of the liver was loose and a large area of inflammatory cells infiltrated,27 differential metabolites such as taurine,glutathione and taurocholic acid were screened out by liver metabolomics,it was mainly enriched in four metabolic pathways:Taurine and hypotaurine metabolism,primary bile acid biosynthesis,glutathione metabolism and purine metabolism;Network pharmacology predicted 21 active components of Abrus cantoniensis,including β-sitosterol,emodin,stigmasterol,abrine,etc.There were 119 intersecting targets between the active components of abrus cantoniensis and cholestasis,and 20 core targets were screened out by PPI network,it involves chemical carcinogenesis-receptor activation,bile secretion,chemical carcinogenesis-DNA adducts and other signaling pathways.Conclusion Abrus cantoniensis has obvious protective effect on cholestasis mice,which may be related to the regulation of bile acid metabolism and glutathione metabolism.