Exploring the Mechanism of Artesunate Intervention in Sepsis-Induced Myocardial Injury Based on Network Pharmacology and Experimental Validation

Objective To investigate the protective effect of Artesunate (AS) on sepsis-induced myocardial injury (SIMI) and its underlying molecular mechanisms, based on network pharmacology and experimental validation.Methods Potential targets and pathways of AS for intervening in SIMI were screened using network pharmacology. A rat sepsis model was established by cecal ligation and puncture to evaluate the cardioprotective effects of AS by measuring serum myocardial injury markers and observing myocardial histopathological changes. Serum levels of inflammatory cytokines and oxidative stress markers were measured to validate the drug's intervention effect. Western Blot was performed to detect the expression of JAK2/STAT3 pathway-related proteins in myocardial tissue to elucidate the potential mechanisms.Results Network pharmacological analysis identified 68 potential therapeutic targets. GO analysis revealed that these targets were mainly enriched in molecular functions such as kinase regulatory activity, while KEGG enrichment analysis showed significant associations with pathways related to inflammatory responses, among others. Molecular docking results indicated excellent binding affinity between AS and core targets such as STAT3. Experimental validation demonstrated that, compared with the CLP group, AS intervention significantly ameliorated myocardial histopathological damage and reduced serum cardiac enzyme levels in septic rats. Moreover, AS significantly decreased serum levels of IL-6 and TNF-α, increased SOD activity, reduced MDA content, and downregulated the protein expression levels of p-JAK2 and p-STAT3 in myocardial tissue.Conclusion Artesunate may exert a protective effect against sepsis-induced myocardial injury by inhibiting the JAK2/STAT3 signaling pathway, thereby alleviating inflammation and oxidative stress. These findings provide compelling pharmacological evidence for the drug repurposing of Artesunate.