BackgroundHepatic ischemia-reperfusion (I/R) injury involves inflammatory necrosis of liver cells as a significant pathological mechanism. Catapol possesses anti-inflammatory activity that is extracted from the traditional Chinese medicine, Rehmannia glutinosa. MethodsThe liver function and histopathology, Oxidative stress, and aseptic inflammatory responses were assessed in vivo, and the strongest dose group was selected. For mechanism, the expression of miR-410–3p, HMGB1, and TLR-4/NF-κB signaling pathways was detected. The dual luciferase assay can verify the targeting relationship between miR-410–3p and HMGB1. Knockdown of miR-410–3p in L02 cells is applied in interference experiments. ResultsCAT pre-treatment significantly decreased the liver function markers alanine and aspartate aminotransferases and reduced the areas of hemorrhage and necrosis induced by hepatic I/R injury. Additionally, it reduced the aseptic inflammatory response and oxidative stress, with the strongest protective effect observed in the high-dose CAT group. Mechanistically, CAT downregulates HMGB1, inhibits TLR-4/NF-κB signaling pathway activation, and reduces inflammatory cytokines TNF-α, and IL-1β. In addition, the I/R-induced downregulation of microRNA-410–3p was inhibited by CAT pre-treatment in vivo and in vitro. HMGB1 was identified as a potential target of microRNA-410–3p using a dual-luciferase reporter assay. Knockdown of microRNA-410–3p abolished the inhibitory effect of CAT on HMGB1, p-NF-κB, and p-IκB-α protein expression. ConclusionsOur study showed that CAT pre-treatment has a protective effect against hepatic I/R injury in rats. Specifically, CAT attenuates the aseptic inflammatory response to hepatic I/R injury in vivo and in vitro by inhibiting the HMGB1/TLR-4/NF-κB signaling pathway via the microRNA-410–3p.