Ginsenoside Rd protects against acute liver injury by regulating the autophagy-NLRP3 inflammasome pathway

Context: Ginsenoside Rd (Rd) is a bioactive compound predominantly found in Panax ginseng C.A. Meyer and Panax notoginseng (Burkill) F.H. Chen ex C.H. Chow, both species belonging to genus Panax in the Araliaceae family. However, its hepatic protective effect against acute liver injury and related mechanistic action remain unexplored. Objective: To investigate the protective effect of Rd against thioacetamide (TAA)-induced acute liver injury and assess its underlying regulatory mechanisms related to autophagy and inflammation. Materials and methods: Forty-eight C57BL/6 mice were treated with saline (control or model group), Rd (12.5 mg/kg, 25 mg/kg or 50 mg/kg), and diammonium glycyrrhizinate (DG, 30 mg/kg) for three days. Then the mice were stimulated with TAA to establish acute liver injury model, excluding the control group. HSC-T6 cells were treated with Rd at concentrations of 2.5, 5, or 10 μM, for 12 hours with or without LPS stimulation at 100 ng/mL. RT-qPCR, immunofluorescence staining and Western blot were employed to analyze the expressions of genes and proteins associated with inflammation and autophagy. To validate the role of Rd in regulating autophagy and inflammation, the autophagy inducers, rapamycin and GSK621, were utilised in reverse validation experiments in cells. Results: Rd exhibited significant hepatic protective effects in mice with acute liver injury. It exhibited strong anti-inflammatory effect by reducing the gene and protein expressions of various pro-inflammatory modulators in liver tissue, and inhibited LPS-induced autophagy and inflammation in HSC-T6 cells.Rd suppressed autophagy in mice via the AMPK/mTOR/ULK1 pathway. The inhibitory effects of Rd on autophagy and inflammation in HSC-T6 cells were partially blocked by rapamycin and GSK621. Discussion and Conclusion: Rd is a promising therapeutic agent to protect liver against TAA-induced acute liver injury.