Sodium Danshensu Attenuates Renal Ischemia-Reperfusion Injury by Suppressing STAT3-Driven Cytokine Signaling and Apoptosis.

objectiveTo evaluate the renoprotective effects and underlying molecular mechanisms of sodium danshensu (SDSS) in renal ischemia-reperfusion (RIR) induced acute kidney injury.

methodsNetwork pharmacology, Weighted Gene Co-expression Network Analysis, single-cell RNA sequencing and machine learning algorithms were integrated to systematically identify SDSS's potential therapeutic targets in RIR. Molecular docking was also employed to confirm key target interactions. Target validation was performed both in vivo and in vitro. In vivo, a rat RIR model was established by occluding bilateral renal arteries, and SDSS (20 mg•kg

resultsThe results of network pharmacology and multiomics analysis identified STAT3, P-STAT3, RELA proto-oncogene (RELA), C-C motif chemokine ligand 2 (CCL2), tumor necrosis factor (TNF), BAX, and CASP3 as therapeutic targets involved in inflammation, apoptosis and immune regulation during RIR progression. More importantly, SDSS significantly reduced the infarction volume and preserved tissue integrity in vivo (P<0.01). RIR upregulated STAT3, BAX, and CASP3 expressions, which SDSS treatment effectively reversed both in vivo and in vitro (P<0.01).

conclusionSDSS alleviates RIR injury by suppressing inflammatory and apoptotic signaling, primarily through downregulation of STAT3, BAX, and CASP3, providing new insights into its therapeutic mechanism and potential clinical application.