Ginsenoside Rg1 alleviates diabetic liver injury and fibrosis by inhibiting the PLC-NFAT2-NLRP3 signaling pathway in T2DM mice

• Rg1 alleviates T2DM-induced liver injury in mice. • Rg1 reduces hepatic lipid deposition and fibrosis in T2DM-induced mice. • Rg1 ameliorates hepatic NLRP3 inflammasome activation in T2DM-induced mice. • Rg1 inhibits PLC-CN-NFAT2 activation to restore calcium homeostasis. Diabetic liver injury (DLI) is a complication that impairs the quality of life of diabetic patients. Ginsenoside Rg1 is hepatoprotective, but its role and mechanism in diabetic liver injury need further investigation. Therefore, using in vivo experiments, we investigated the implication of ginsenoside Rg1 on hepatic lipid deposition, hepatic injury, hepatic fibrosis, and associated inflammation using a type 2 diabetes mellitus (T2DM) mouse model. We observed that Rg1 significantly ameliorated hepatic lipid deposition and hepatic fibrosis in T2DM mice. Meanwhile, Rg1 significantly reduced the expression of CD36, p-PLC, CaN, and NFAT2 and inhibited the activation of the NLRP3 inflammasome. Molecular docking results indicated that Rg1 binds well to PLC. In vitro experiments also demonstrated that Rg1 can inhibit calcium overload by regulating PA + HG-induced PLC activation in HepG2 cells. These results suggest that Rg1 treatment prevents T2DM-induced liver injury by inhibiting hepatic lipid deposition and the PLC-NFAT2-NLRP3 signaling pathway.