Network pharmacology, molecular docking technology integrated with pharmacodynamic study to explore the potential targets and mechanism of Xinkeshu tablets against myocardial ischemia reperfusion injury

Xinkeshu tablets (XKST) is a Chinese patent medicine (CPM) against cardiovascular diseases. However, the specific action and mechanism of XKST against Myocardial ischemia reperfusion injury (MIRI) have not been clarified and discussed in detail. This study aims to discover the potential targets and mecha-nism of XKST in the treatment of MIRI. The therapeutic effects of XKST on MIRI in rats were evaluated by pharmacodynamics indexes, including myocardial enzyme content, cardiac troponin content, myocar-dial infarction rate, 2,3,5-triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) stain-ing. The intersection of compound targets and disease targets were obtained and the coincidence targets were used to construct a compound-target network. We further performed GO and KEGG enrichment analysis on the targets to study its potential molecular mechanism. Differentially expressed genes (DEGs) analysis based on Gene expression omnibus (GEO) database was used to further identify core targets. Finally, molecular docking study was approved for core targets and quality markers of XKST. The phar-macodynamics results indicated that XKST had a good therapeutic effect on MIRI rat model. Additionally, our research showed that the protein targets ALOX12, MMP8 and HSD11B1 may be potential therapeutic core targets of XKST in the treatment of MIRI. Furthermore, it may play therapeutic roles through AGE -RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, prostate cancer, TNF signal-ing pathway and fluid shear stress and atherosclerosis, etc. This study reveals the potential targets and mechanism of XKST in the treatment of MIRI, and provides a reference for subsequent basic research.(c) 2022 Elsevier B.V. All rights reserved.