| Popis: |
The present work was aimed to gain more insight into the molecular mechanisms of Salvia miltiorrhiza Bunge and Carthamus tinctorius L herb pair (SMCTHP) in treating myocardial ischemia (MI) through network pharmacology and in vivo experiments. Firstly, various electronic databases and literatures-mining were utilized to acquire and screen out the bioactive compounds of SMCTHP and potential therapeutic targets of myocardial ischemia (MI). Subsequently, functional enrichment analysis was carried out to obtain a more radical understanding of SMCTHP against MI via the DAVID database. PPI network was established and analyzed to determine the hub targets. Finally, we used the acute myocardial ischemia (AMI) rat model to evaluate the cardioprotective effects of SMCTHP, and TUNEL assay and Western blotting analysis were used to measure the apoptotic rate and validated the hub targets and key pathways, respectively. A total of 92 bioactive compounds of SMCTHP and 245 overlapping targets between SMCTHP and MI were identified from these databases. By performing functional enrichment analysis, the anti-MI targets of SMCTHP were highly correlated with the apoptosis process, and the key functional pathways may be the PI3K/AKT and NF-κB pathways. Then, the hub targets of the PPI network contained AKT1, IL6, TNF, VEGFA, MAPK1, STAT3, RELA, MMP9, CASP3, and TLR4. In vivo experiment demonstrated that SMCTHP significantly improved myocardial ischemic injury, reduced cardiomyocyte apoptosis in ischemic rat myocardium. In addition, SMCTHP could markedly upregulate the expression of phosphorylated (p)-AKT, and obviously downregulated the expressions of TLR4 and p-NF-κBp65 in the myocardial tissue of AMI rats. This study revealed that SMCTHP may ameliorate ISO-induced myocardial ischemic injury via exhibiting the anti-apoptotic effects potentially be regulating the AKT and TLR4/NF-κB pathways. |
