Salvianolic acid a alleviates myocardial ischemia-reperfusion injury in rats via SIRT1-mediated inhibition of oxidative stress and inflammation
Abstract
Ethnopharmacological relevance
Salvia miltiorrhiza (SM) is a classic traditional Chinese medicine with anti-inflammatory and antioxidant properties, and salvianolic acid A (SAA) is its main bioactive component. Myocardial ischemia-reperfusion injury (MIRI) is common in ischemic heart disease treatment, mainly caused by inflammation and oxidative stress.
Aim of the study
To clarify the role of SIRT1 (Sirtuin 1) in SAA's protection against MIRI and the underlying signaling pathways.
Materials and methods
The potential targets of SAA and MIRI were identified using SwissTargetPrediction, SEA, TargetNet, GeneCards, OMIM and CTD databases. Gene Ontology Enrichment (GO) and Signaling Pathway Enrichment (KEGG) analyses were performed on these targets. Molecular docking examined SIRT1-SAA interactions. In vivo MIRI models were established by left anterior descending coronary artery ligation in rats, while H9c2 cell hypoxia-reoxygenation (H/R) models served for in vitro studies. Western blotting (WB), co-immunoprecipitation (Co-IP) assay, immunofluorescence (IF) staining and Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) were employed to validate the effects of SAA on MIRI therapy. SIRT1 siRNA knockdown confirmed its regulatory role in SAA's antioxidant and anti-inflammatory actions against MIRI.
Results
SAA alleviated MIRI dose-dependently by inhibiting inflammation and oxidative stress, with high binding affinity to SIRT1 (molecular docking). SAA upregulated SIRT1 expression and exerted antiapoptotic effects, activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and suppressing the nuclear factor kappa-B (NF-κB) pathway via SIRT1.
Conclusion
SAA mitigates MIRI-induced oxidative stress and inflammation by activating SIRT1, which regulates the PGC-1α/Nrf2/HO-1 and NF-κB pathways. This confirms SIRT1 as the key upstream mediator of SAA's cardioprotective effects, supporting SAA as a potential therapeutic agent for MIRI.