[Effects of gambogic acid on liver function in rats with chronic hepatitis B by adjusting Sirt1/FoxO1 pathway]

This study investigated the effects of gambogic acid(GA) on liver function in rats with chronic hepatitis B(CHB) via the silent information regulator 2 homolog 1(Sirt1)/forkhead box transcription factor O1(FoxO1) signaling pathway. A CHB rat model was established using hepatitis B virus(HBV) antigen. Another 10 healthy rats injected with an equal volume of physiological saline served as the control group. After successful modeling, rats were divided into a CHB group, low-dose GA(L-GA, 50 mg·kg~(-1) GA by gavage) group, high-dose GA(H-GA, 100 mg·kg~(-1) GA by gavage) group, and GA+EX527(100 mg·kg~(-1) GA by gavage combined with intraperitoneal injection of 5 mg·kg~(-1) EX527, a Sirt1 inhibitor) group. Rats in the control and CHB groups received equal volumes of physiological saline by gavage and intraperitoneal injection. Each group consisted of 10 rats, and treatment was administered once daily for 4 consecutive weeks. Serum levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), and total bilirubin(TBIL) were measured using an automated biochemical analyzer. ELISA was performed to determine the serum levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α). RT-qPCR was used to detect viral expression in liver tissue. HE staining was performed to observe pathological changes in liver tissue, and Masson staining was used to evaluate hepatic fibrosis. Western blot was used to detect the protein expression of Sirt1 and acetylated(Ac)-FoxO1/Fox O1 in liver tissue. The results showed that liver tissue in the CHB group exhibited marked swelling, disordered cellular arrangement, extensive inflammatory cell infiltration, and collagen deposition. Treatment with L-GA and H-GA progressively alleviated pathological injury and collagen deposition in liver tissue, whereas pathological injury and collagen deposition were further aggravated in the GA+EX527 group. Compared with the control group, the CHB group showed significantly increased levels of ALT, AST, TBIL, IL-1β, TNF-α, and HBV DNA, and significantly decreased expression of Sirt1 and Ac-FoxO1/Fox O1(P<0. 05). Compared with the CHB group, the L-GA and H-GA groups showed significantly decreased levels of ALT, AST, TBIL, IL-1β, TNF-α, and HBV DNA, and significantly increased expression of Sirt1 and Ac-FoxO1/Fox O1(P<0. 05), with more pronounced changes observed in the H-GA group(P<0. 05). Treatment with GA+EX527 significantly reversed the changes in the above indicators observed in the H-GA group(P<0. 05). In conclusion, GA may improve liver function in CHB rats by activating the Sirt1/Fox O1 signaling pathway, thereby inhibiting inflammatory responses and hepatic fibrosis and reducing viral expression in liver tissue.