Effect of Ursolic Acid Extracted from Hippophae rhamnoides L. on FXR Signaling Pathway in Liver of Rats with Alcoholic Liver Injury

Objective: To investigate the effect of ursolic acid extracted from Hippophae rhamnoides L. on the expression of key proteins of hepatic farnesoid X receptor (FXR) signaling pathway in rats with alcoholic liver injury. Methods: The 6-week-old SPF SD rats were divided randomly into 4 groups: The normal control group, the alcohol model group, the ursolic acid control group and the ursolic acid+alcohol group, 9 mice in each group. The rats were administered by intragastric administration for eight consecutive weeks. The pathological changes of hepatic tissues in rats was observed by hematoxylin eosin (H&E) staining. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the content of total bile acid (TBA) in serum, and the content of triglyceride (TG) and total cholesterol (TC) in liver of rats were tested. The content of the serum cytokine including tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interleukin 10 (IL-10) was detected by enzyme linked immunosorbent assay (ELISA). The expression of FXR signal pathway related proteins in liver tissue of rats was detected by Western blotting. Results: Compared with the normal control group, there were fat vacuoles of different sizes and a large number of inflammatory cells in the liver of the alcohol model group. The activities of ALT, AST, the levels of TNF-ɑ, IL-1β, the content of TBA in serum and the content of TG, TC in liver were increased significantly (P<0.05), and the level of IL-10 was decreased significantly (P<0.05). After the ursolic acid intervention, hepatic steatosis was improved significantly and inflammatory cell infiltration was decreased. The activities of ALT, AST, the levels of TNF-ɑ, IL-1β and the content of TBA in serum and the content of TG in liver were significantly decreased in different degrees (P<0.05), and the level of IL-10 was significantly increased (P<0.05). The Western blotting results showed that compared with the normal control group, the protein expression of FXR in the model group was decreased significantly (P<0.05), while the protein expression of CYP7A1 and SREBP-1c were increased significantly (P<0.05). After ursolic acid intervention, the protein expression of FXR expression was increased significantly, while the protein expression of CYP7A1 and SREBP-1c were decreased significantly, and the difference was statistically significant (P<0.05). Conclusion: The ursolic acid extracted from Hippophae rhamnoides L. can improve alcohol induced liver injury significantly, and its mechanism may be related to up regulating hepatic FXR, inhibiting the protein expression of CYP7A1 and SREBP-1c, thus regulating bile acid homeostasis and lipid metabolism.