Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-Kappa B Signaling and NLRP3 Inflammasome

Background and Aims: The effect of ginsenoside Rb1 on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-in-duced acute liver injury (ALI) is unknown. The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms. Methods: Mice were pre-treated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment, to induce ALI. The survival rate was monitored every hour for 24 h, and se-rum biochemical parameters, hepatic index and histopatho-logical analysis were evaluated to measure the degree of liver injury. ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum. Im-munohistochemistry staining, RT-PCR and western blotting were performed to evaluate the expression of toll-like re-ceptor 4 (TLR4), nuclear factor-kappa B (NF-Kappa B), and NLR family, pyrin domain-containing 3 protein (NLRP3) in liver tissue and Kupffer cells (KCs). Results: Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%, significantly ameliorated the increased alanine and aspartate transaminase, restored the hepatic pathological changes and reduced the levels of oxidative stress and in-flammatory cytokines altered by D-GalN/LPS. Compared to the control group, the KCs were increased in the D-GalN/ LPS groups but did not increase significantly with Rb1 pre-treatment. D-GalN/LPS could upregulate while Rb1 pre-treatment could downregulate the expression of interleu-kin (IL)-1 beta, IL-18, NLRP3, apoptosis associated speck-like protein containing CARD (ASC) and caspase-1 in isolated KCs. Furthermore, ginsenoside Rb1 inhibited activation of the TLR4/NF-Kappa B signaling pathway and NLRP3 inflamma-some induced by D-GalN/LPS administration. Conclusions: Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-Kappa B signaling pathway and NLRP3 inflammasome activation.