Oridonin alleviates d‐GalN/LPS‐induced acute liver injury by inhibiting NLRP3 inflammasome

Abstract Acute liver injury (ALI) is a serious syndrome that is associated with high mortality, but there are few effective treatments. The activation of NLRP3 inflammasome is associated with ALI. Oridonin is a natural substance with an anti‐inflammatory effect and has been reported to be an inhibitor of NLRP3. The aim of this study was to investigate the protective effect of oridonin on d ‐galactosamine ( d ‐GalN)/lipopolysaccharide (LPS)‐induced ALI and whether the effect is mediated by NLRP3. Mice were pretreated with oridonin (5 or 10 mg/kg) for 3 days. Then, they were injected with d ‐GalN (400 mg/kg) and LPS (40 μg/kg). The levels of inflammatory factors were measured by RT‐PCR, Western blot, and enzyme‐linked immunosorbent assay. We confirmed that oridonin significantly alleviated ALI induced by d ‐GalN/LPS in mice. Oridonin markedly decreased the inflammatory response by reducing the levels of inflammatory cytokines. More importantly, oridonin markedly reduced the expression of NLRP3, caspase‐1, IL‐18, and IL‐1β. This study showed that oridonin has a protective effect on d ‐GalN/LPS‐induced ALI, and the underlying mechanisms may be associated with the inhibition of the NLRP3 inflammatory pathways.