Effect of Cistanche deserticola phenylethanoid glycoside on lipid metabolism homeostasis in alcoholic liver disease model mice and mechanism
Objective:Constructed a mouse model of alcoholic liver disease(ALD)using Lieber-Decarli liquid alcohol feed to investigate the regulation of lipid metabolism homeostasis in alcoholic fatty liver disease by Cistanche deserticola phenylethanoid glycoside(CPhGs).Methods:The 48 female C57BL/6N mice were randomly divided into control group,control + 700 mg·kg-1 CPhGs group,model group,model + 175 mg·kg-1 CPhGs group,model +350 mg·kg-1 CPhGs group and model +700 mg·kg-1 CPhGs group,with 8 mice in each group.The mouse model of alcoholic liver disease was established based on NIAAA method,and different concentrations of CPhGs were administered by gastric gavage for 14 days.Serum ALT,AST,TG,TC,HDL-C and LDL-C were detected.HE and oil red O staining were used to observe the pathological changes of liver.The contents of TG,TC,HDL-C and LDL-C in liver homogenate were detected by colorimetry.Western blot was used to detect the expression of PPARα protein in liver tissue.Combined with LC-MS/MS technology,targeted lipid metabolism in liver was detected,and differential metabolites were screened and the related metabolic pathways were analyzed.Results:Compared with the model group,the contents of serum AST,ALT,TG,TC and LDL-C in model +700 mg·kg-1 CPhGs group decreased significantly,while HDL-C increased.HE and oil red O staining results showed that the accumulation of liver lipid droplets decreased significantly in the model +700 mg·kg-1 CPhGs group.WB results showed that the expression of PPARα protein increased in the model +700 mg·kg-1 CPhGs group,compared to the model group.Sixteen different metabolites were screened from lipid metabolism,and the pathway analysis showed that CPhGs could improve alcoholic liver disease in mice mainly by regulating the metabolic pathways such as glycerophosphate metabolism,phosphatidylinositol signaling system and phosphoinositide metabolism.Conclusion:CPhGs can improve lipid homeostasis of ALD by promoting PPARα expression,increasing PC synthesis,regulating related lipid metabolism pathways.