Exploring the Protective Mechanism of Xuebijing Injection Against Sepsis

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Purpose: Xuebijing (XBJ) injection is a traditional Chinese medicine (TCM) injection prepared using modern pharmaceutical techniques. Approved as a State Category II New Drug for sepsis, XBJ has demonstrated significant clinical efficacy in China. However, the bioactive components of XBJ and the mechanisms underlying its anti-sepsis effects remain to be fully elucidated. This study aimed to elucidate the regulatory network among herbs, compounds, genes, and signaling pathways. Methods: We conducted a network pharmacology analysis by integrating published RNA-sequencing data from the BioProject database and experimental evidence from 27 relevant studies identified in PubMed. And the anti-sepsis effects of XBJ and its main component, Hydroxysafflor Yellow A, were validated in a CLP-induced murine model. Results: Our results demonstrate that XBJ modulates 21 target genes through at least 18 of its bioactive compounds (e.g. Quercetin, Kaempferol). The majority of these genes, including IL6, TNF, and HMGB1, were down-regulated after XBJ treatment. Using a cecal ligation and puncture (CLP)-induced murine sepsis model, we demonstrated that by 24 hours post-operation, the survival rate in the XBJ-treated group was twice that of the PBS-treated group (66.7% vs. 33.3%). Finally, a comprehensive herb-compound-gene-pathway regulatory network was established to illustrate the potential mechanisms of action. Conclusion: In summary, this study reveals that XBJ may alleviate sepsis by modulating target genes via its compounds, primarily through anti-inflammatory and antioxidant pathways. This study provides a systematic elucidation of XBJ’s anti-sepsis mechanism, and the research strategy established here offers a valuable framework for investigating the mechanisms of other complex traditional Chinese medicine formulae. The infographic illustrates the analysis of Xuebijing, starting with databases TTD, TCMIP, CTD, TCMSP leading to target genes of sepsis and Xuebijing-containing compounds. A Venn diagram shows the intersection of XBJ and SEPSIS with 63 common elements. Network pharmacology is depicted with connections between compounds like Quercetin and genes such as MAPK3, PTGS2 and NFKBIA. Published reports are shown with a bubble chart indicating various genes and methods. Molecular docking images are displayed, followed by a diagram linking herbs, compounds, genes and pathways, including the Toll-like receptor signaling pathway and HIF-1 signaling pathway.Schematic diagram of research strategy using network pharmacology, molecular docking, and literature review to decipher Xuebijing injection’s anti-sepsis mechanism. Keywords: sepsis, Xuebijing injection, target gene, network pharmacology, anti-inflammatory

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