Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Liver cancer has a high incidence and poor prognosis. Curcumin is a natural compound with anti-tumor activity, but its effects on the STAT3 signaling pathway and the bile acid enterohepatic circulation in liver cancer models remain unclear. Objectives: To investigate the effects of curcumin on the STAT3 signaling pathway and bile acid enterohepatic circulation in a mouse model of liver cancer. Methods: A liver cancer model was established in C57BL/6J mice, which were divided into a sham surgery group, a model control group, low-, medium- and high-dose curcumin groups, a STAT3 inhibitor group, a combination intervention group and a cisplatin positive control group. HE staining was used to observe the pathological morphology of liver tissue. Serum biochemical indicators and IL-6 and TGF-?1 levels were measured. STAT3 pathway proteins were detected by Western blot and related gene expression was analyzed by qRT-PCR. Results: Curcumin dose-dependently inhibited STAT3 signaling activity and reduced the p-STAT3/total STAT3 ratio (P<0.05). In the high-dose curcumin group, serum ALT, AST and TB levels decreased from (254.55±56.14)U/L, (542.01±71.28)U/L and (42.98±8.21)?mol/L to (47.98±10.68)U/L, (135.24±24.12)U/L and (7.91±1.36)?mol/L, respectively (all P<0.05). Curcumin upregulated the expression of BSEP, NTCP and FXR, downregulated Cyp7a1 and upregulated the expression of intestinal Fgf15 and Asbt. Conclusion: Curcumin alleviates liver injury and inflammation while ameliorating bile acid enterohepatic circulation by inhibiting the STAT3 signaling pathway.