Abstract
BACKGROUND: Sepsis is a critical condition triggered by infection and characterized by systemic inflammation and subsequent multiorgan failure. Chaihuang Qingfu Pill (CHQF), an in-hospital formulation developed by Hunan Provincial People's Hospital, is derived from the traditional Chinese medicine compound Qingyi Decoction through optimized herbal compatibility. It possesses pharmacological activities including heat-clearing and purgation, choleretic and anti-jaundice effects, as well as Qi-regulation and mass-resolving properties. Clinically, CHQF is primarily used in the treatment of cholecystitis, pancreatitis, and hepatitis, and has shown potential therapeutic effects in alleviating sepsis-associated liver injury. However, the precise molecular mechanisms and omics-based investigations of CHQF in the context of sepsis remain poorly understood. The NF-κB signaling pathway serves as a central regulatory hub of the inflammatory response. Its activation leads to the excessive expression of pro-inflammatory mediators and cytokines, thereby exacerbating tissue damage and promoting the progression of inflammatory diseases. Consequently, targeting the NF-κB pathway may represent an effective therapeutic strategy for the treatment of sepsis. This study aims to systematically investigate the molecular basis of CHQF in the mitigation of sepsis-associated liver damage. PURPOSE: To explore the mechanism of CHQF for the treatment of sepsis-induced liver injury. METHODS: A sepsis mouse model was established via cecal ligation and puncture (CLP). The pharmacological mechanisms of CHQF were explored using network pharmacology, transcriptomics, and metabolomics, which enabled the identification of potential therapeutic targets and pathways, as further validated by in vivo and in vitro experiments. RESULTS: CHQF administration significantly improved the survival rates, reduced systemic inflammation, and restored liver function in CLP-induced sepsis mice, while also mitigating liver tissue injury. Network pharmacological analysis revealed paeoniflorin, quercetin, hyperforin, and wogonin as the core bioactive compounds of CHQF. Transcriptomic profiling identified key targets, including CD14, CXCL2, CCL2, BIRC5, and CXCL8, and demonstrated a significant downregulation of inflammatory cytokines such as TNF-α, IL-6, IL-1β, IL-17, CCL2, CCL3, CCL4, CXCL2, CXCL3, and CXCL5, alongside NF-κB signaling pathway inhibition. Metabolomic analysis indicated that CHQF treatment reduced the levels of sepsis-related metabolites, including lysophosphatidylcholine (22:6), lysophosphatidylcholine (18:1), 1-LGPC, and C17-sphinganine. CONCLUSION: Collectively, these findings suggest that CHQF alleviates sepsis-induced liver injury by modulating the inflammatory response via NF-κB signaling pathway inhibition. This study provides novel insights into the complex molecular mechanisms underlying the therapeutic effects of CHQF in sepsis and enhances the understanding of the pharmacological actions of traditional Chinese medicine in managing sepsis.