Dejun Zhang

Introduction: The aim of this study was to investigate the pharmacological mechanism of Wuwei Yuganzi San (WYS) in treating coronary heart disease (CHD) using network pharmacology and molecular docking. Methods: The main active components, related targets, and the target genes related to WYS were investigated by the databases Traditional Chinese Medicine Systems Pharmacology and related articles. Information on the target genes of CHD was acquired through the OMIM database and GeneCards database, and the NCBI Gene Expression Omnibus DataSets (GSE71226) were used to acquire target genes of CHD. A Venn diagram was used to show the common targets of WYS and CHD. The compound-target-disease network was built up by Cytoscape 3.7.2, and the protein–protein interaction (PPI) network was acquired through the STRING database. ClusterProfiler and Pathview packages in RStudio software were used to conduct gene ontology enrichment analysis and KEGG pathway enrichment analysis to reveal the underlying mechanism. Finally, AutoDock Vina software was used to assess the binding affinity of significant ingredients and hub genes. Results: Thirty-four key ingredients of WYS in CHD were screened, which related to 59 targets in CHD. According to the results of enrichment analysis, 59 items in the biological process, 15 items in the molecular function, 10 items in the cellular component, and 52 signaling pathways were associated with efficacy. These processes and pathways were essential for cell survival and were related to several crucial factors of CHD, including a disintegrin and metalloprotease 17 (ADAM17), aldo-keto reductase family 1 member C2 (AKR1C2), albumin (ALB), protein kinase B (AKT1), and alcohol dehydrogenase 1C (ADH1C). Based on the outcomes of the PPI network, we selected ADAM17, AKR1C2, ALB, AKT1, ADH1C, and putative ingredients (sennoside D_qt, quercetin, and procyanidin B-5,3'- O-gallate) to perform molecular docking validation. From the molecular docking outcomes, some vital targets of CHD (including ADAM17, AKR1C2, ALB, AKT1, and ADH1C) could be related to form a stable combination with the putative ingredients of WYS. Conclusions: The network pharmacology and molecular docking study elucidated basically the mechanism of WYS in the treatment of CHD.

Purpose: The objective of this study was to identify the potential regulatory mechanisms, diagnostic biomarkers, and therapeutic drugs for heart failure (HF). Methods: Differentially expressed genes (DEGs) between HF and non-failing donors were screened from the GSE57345, GSE5406, and GSE3586 datasets. Database for Annotation Visualization and Integrated Discovery and Metascape were used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses respectively. The GSE57345 dataset was used for weighted gene co-expression network analysis (WGCNA). The intersecting hub genes from the DEGs and WGCNA were identified and verified with the GSE5406 and GSE3586 datasets. The diagnostic value of the hub genes was calculated through receiver operating characteristic analysis and net reclassification index (NRI). Gene set enrichment analysis (GSEA) was used to filter out the signaling pathways associated with the hub genes. SYBYL 2.1 was used for molecular docking of hub targets and potential HF drugs obtained from the connection map. Results: Functional annotation of the DEGs showed enrichment of negative regulation of angiogenesis, endoplasmic reticulum stress response, and heart development. PTN, LUM, ISLR, and ASPN were identified as the hub genes of HF. GSEA showed that the key genes were related to the transforming growth factor-β (TGF-β) and Wnt signaling pathways. Sirolimus, LY-294002, and wortmannin have been confirmed as potential drugs for HF. Conclusion: We identified new hub genes and candidate therapeutic drugs for HF, which are potential diagnostic, therapeutic and prognostic targets and warrant further investigation.

Background: Coronary heart disease (CHD) is a chronic cardiovascular disease across the world, which poses numerous threats to mankind. Wuwei Yuganzi San (WYS) is a famous traditional Tibetan medicine prescription. It has been confirmed effective in the treatment of CHD, but its specific mechanism remains still unclear. Objective: To elucidate the main pharmacological action of WYS in treating CHD and investigate the underlying multiple mechanisms of its multi-ingredient-multi-target by network pharmacology.Methods: Firstly, active ingredients of WYS and connected targets of five herbs were retrieved by using traditional Chinese medicine systems pharmacology (TCMSP) and screening literature. Then, genome explanation databases (OMIM and GeneCards) were used to acquire targets related to CHD. The protein-protein interaction (PPI) network was built using the mutual targets filtering genes through protein interaction. Next, a network diagram could be established with the help of Cytoscape 3.8.2. And, STRING platform was used to construct a protein interaction network. Finally, GO and KEGG analyses were analyzed to further elucidate biological process enrichment.Results: After the screening, 36 active ingredients and 202 related targets in WYS in addition to 952 disease-related targets were acquired. A total of 37 key targets including AKT1, ESR1, and EGFR were screened in the PPI network. These targets were mostly concentrated on the transmembrane receptor protein tyrosine kinase signaling pathway, cellular response to growth factors stimulus, and response to growth factor. The KEGG enrichment demonstrated that the MAPK signaling pathway, P13K/AKT signaling pathway, Ras signaling pathway, and other corresponding signaling pathways were closely related to CHD.Conclusions. WYS plays a significant role in the treatment of CHD. And this study provides a novel approach to disclose the therapeutic mechanisms of WYS on CHD.