Hepatoprotective Effects of Lonicera japonica Flos Against Acute Liver Injury: Insights from an Integrative Multi-omics and Experimental Approach

Abstract Background Acute liver injury (ALI) is a severe hepatic condition with high mortality and few therapeutic options aside from liver transplantation. Lonicera japonica Flos (LJ), a traditional herbal medicine, has been reported to have anti-inflammatory and hepatoprotective activities; however, the underlying mechanisms remain insufficiently clarified. Methods In this study, an integrative approach was used to investigate the effects of LJ on liver injury by combining network pharmacology, molecular docking, and experimental validation. Computational analyses were used to predict the potential targets and enriched pathways of LJ-derived active compounds on ALI. These predictions were subsequently validated in lipopolysaccharide (LPS) induced ALI murine models and LPS-stimulated HepG2 cells through biochemical assays and histological staining with evaluation of HIF-1α/IL-1β signaling pathway-related molecules. Results Network pharmacology highlighted that the HIF-1 signaling pathway is closely related to the potential mechanism of LJ on ALI. In silico docking demonstrated that loganin and loganic acid, main components of LJ, have potentially strong binding affinities on HIF-1α. Based on these predicted results, LJ lowered serum AST and ALT, alleviated histopathological injury, and suppressed hepatic TNF-α, IL-6, and IL-1β expression in LPS-induced ALI mice. In HepG2 cells, LJ inhibited cleaved IL-1β and HIF-1α protein expression without cytotoxicity in response to LPS, thereby dampening multiple inflammatory cascades. Conclusion Overall, LJ exerts hepatoprotective effects against LPS-induced ALI by targeting several interconnected pathways. These findings support LJ as a potential therapeutic candidate for inflammatory liver disease and demonstrate the value of combining computational prediction with experimental confirmation to investigate traditional herbal medicines. Graphical Abstract