Identification of CCR2 as a hub in septic myocardial injury and cardioprotection of silibinin.

Myocardial injury is a serious complication of sepsis associated with high morbidity and mortality. Our previous work has confirmed that silibinin (SIL) alleviates septic myocardial injury, but the specific molecular mechanism has not been fully elucidated. This study aimed to identify its potential targets through network pharmacology combined with experimental verification. Firstly, a total of 29 overlapping genes between sepsis and SIL targets were obtained from RNA-seq analysis and the known databases. Subsequently, KEGG and GO analysis showed that these genes were enriched in immune response and cytokine-cytokine receptor interaction pathways. Notably, CCR2 was identified as an important candidate hub by protein-protein interaction analysis and molecular docking approach. In vivo experiments showed that SIL treatment significantly improved survival rate and cardiac function in septic mice, accompanied by decreased CCR2 expression. Moreover, in vitro experiments obtained the similar results. Especially, CCR2 siRNA attenuated inflammation response. In conclusion, this study systematically elucidated the key target of SIL in the treatment of septic myocardial injury. These findings provide valuable insights into the targets of sepsis and offer new avenues for exploring drug effect systematically. [Display omitted] • This study provides a rich resource of disease-drug interaction targets and the complex pharmacological network was constructed. • CCR2 was identified as an important candidate hub. • Experiments validation showed that SIL treatment protected septic myocardial injury, accompanied by decreased CCR2 expression. • CCR2-governed signaling plays an important role in the etiology of septic myocardial injury and cardioprotection of SIL. [ABSTRACT FROM AUTHOR]