茯苓水提物对抗柴胡皂苷 A 引起的肝损伤机制OA

Objective To study the effect and mechanism of water extract of Poria cocos in alleviating liver injury caused by saikosaponin A(SSA).Methods C57BL/6 mice were randomly divided into normal control group,saikosaponin A model group,low-dose Poria cocos treat group and high-dose Poria cocos treat group.A liver injury model was established by intragastric administration of SSA,the treatment was given by gavage of the water extract of Poria cocos.Detect the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the serum of mice,as well as the levels of triglycerides(TG)and cholesterol(TC)in the serum and liver.The toxic targets of SSA acting on Poria cocos were screened by network pharmacology methods,and the cell death-related pathways were constructed from them.In vitro experiments were conducted using AML12 hepatocytes to detect the effects of water extract of Poria cocos and SSA on cell survival rate.The effects of the water extract of Poria Cocos and SSA on cell survival rate were detected,and the expression of cell death related proteins was detected by Western blotting.Results The high-dose Poria cocos group improved survival rates in mice,significantly reduced the levels of serum ALT and AST in mice(P<0.001,P<0.01),and the contents of TC and TG in serum and liver(P<0.05).Network pharmacology screening identified 46 potential targets for Poria cocos intervention in SSA-induced hepatotoxicity.KEGG analysis suggested involvement of the apoptosis signaling pathway,with key targets including Bcl-2,CASP3,and CASP9.In cell experiments demonstrated that the high-dose Poria cocos group could significantly increase cell survival rate(P<0.05),down-regulate the protein expressions of cleaved-caspase-3 and cleaved-caspase-9(P<0.05,P<0.01),and enhance the protein expression of Bcl-2(P<0.01).Conclusion Poria cocos water extract significantly ameliorates SSA-induced liver injury,the mechanism may be related to blocking the mitochondrial-mediated apoptotic pathway triggered by SSA.