Protective effects of Dachengqi Decoction in sepsis-associated liver injury based on network pharmacology analysis and experimental validation

Ethnopharmacological relevance Dachengqi Decoction (DCQD), a traditional formula from Treatise on Exogenous Febrile Disease, purges heat and preserves Yin. Previous studies indicate its efficacy against sepsis-associated liver injury (SALI), but its active components and mechanism remain unclear. Aim of the study To elucidate the effective components and mechanism of DCQD on SALI through network pharmacology and experimental validation. Materials and methods Active compounds and targets of DCQD were screened via TCMSP, while SALI-related targets were obtained from DisGeNET, OMIM, and GeneCards. A "DCQD-compounds-targets-disease" network was constructed using Cytoscape, followed by GO/KEGG enrichment analysis. The compound-target interactions were assessed via molecular docking. The protective effect and mechanism of DCQD on SALI were validated in vivo. Results 35 compounds and 194 related targets of DCQD were screened, 508 genes were predicted as SALI related targets. 62 potential therapeutic targets of DCQD for SALI were selected, in which 11 hub targets were obtained. GO and KEGG analysis implicated multiple signaling mechanisms. Molecular docking confirmed strong binding between key compounds and targets. In SALI mice, DCQD reduced inflammatory cytokines, oxidative stress, apoptosis, and improved intestinal barrier function. Mechanistically, DCQD exerted hepatoprotective effects by activating the PI3K/AKT signaling pathway. Conclusions DCQD alleviated SALI by suppressing inflammation, oxidative stress, apoptosis, and enhancing intestinal barrier integrity via the activation of PI3K/AKT pathway.