OBJECTIVE: To investigate the protective effect of total saponins of (TSPJ) against CCl-induced acute liver injury (ALI) in rats and explore the underlying pharmacological mechanisms.
METHODS: Male SD rat models of CCl-induced ALI were given intraperitoneal injections of distilled water, 100 mg/kg biphenyl bisabololol, or 50, 100, and 200 mg/kg TSPJ during modeling (=8). Liver functions (AST, ALT, TBil and ALP) of the rats were assessed and liver pathologies were observed with HE staining. Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue; ELISA was used to determine the levels of T-SOD, GSH-P, and MDA. Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue.
RESULTS: Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI. In the rat models of ALI, treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl-induced increase of serum levels AST, ALT, ALP, TBil and MDA and decrease of T-SOD and GSH-P levels (all < 0.01). The rat models of ALI showed significantly increased expression of p-NF-κB ( < 0.01), decreased expressions of PI3K, p-Akt and SIRT6 proteins, and elevated expression levels of p-NF-κB, TNF-α and IL-6 proteins in the liver, which were all significantly improved in the treatment groups ( < 0.05 or 0.01).
CONCLUSION: TSPJ can effectively alleviate CCl-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver regulating the PI3K/Akt and SIRT6/NF-κB pathways.
