Acanthoic Acid Improves Non-alcoholic Fatty Liver Disease By Regulating And Controlling The Signaling Pathway Of FXR

Objective:Acanthopanaxic acid,which is a kind of pheromone diterpene material,derived from the root of the Acanthopanax root,the previous study shows that Acanthopanax has a good liver protection,our study used L-D high fat diet diet to induce NAFLD of mouse,and the cells were induced to differentiate into adipocytes.The effect of Acanthopanax senticosus on NAFLD and the specific regulatory mechanism were discussed.Methods:The animal model of nonalcoholic fatty liver was induced by feeding Lieber-DeCarli liquid fat diet daily for 8 weeks.Mice were given different doses(20mg/kg or 40mg/kg)of Acanthopanax senticosus,7 times per a week for 12 weeks.Serum and liver were collected at-80℃.The activities of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)were measured.H&E,oil red staining,Nilered,immunohistochemical staining were used to observe the changes of liver histopathological.The expression levels of α-SMA,Collagen-I and FXR1 and so no were detected by Western blotting and RT-PCR.The logarithmic phase of 3T3-L1 preadipocytes was incubated with DMEM which contains DMI for 2 days,and then incubated with addition of insulin and containing different concentrations(0,1,3,5μmol/l)for 8 days,changed the dmem for 2 days.The expression levels of FXR1 and SREBP1 were determined by Western blotting and RT-PCR analysis.Results:In vivo experiments,compared with the Lieber-DeCarli(L-D)high fat diet group,Acanthopanax acid inhibited the increase of serum ALT,AST,TG in non-alcoholic fatty liver mice caused by high fat diet;Acanthopanax acid inhibited the expression of α-SMA and Collagen-I induced by high fat diet and activated the expression of LXRs and FXR1,thereby inhibited the production of SREBP1,further inhibited the synthesis and accumulation of fatty acids.In vitro experiments,Acanthopanax can significantly inhibit the expression of SREBP1 induced by cell differentiation in a dose-dependent manner,while activating the expression of LXRs and FXR1,thereby inhibiting lipid deposition in lipid cells.Conclusion:Acanthopanax acid may regulate LXRs by regulating FXR1,thereby modulating fatty acid synthesis,inhibiting the formation of nonalcoholic fatty liver in mice induced by high fat diet,and inhibiting differentiation of adipocytes by activating FXR1...