Network pharmacology-based strategy for predicting active ingredients and potential targets of Yangxinshi tablet for treating heart failure. (12th June 2018)

• Record Type: Journal Article
• Authors: Chen, Langdong; Cao, Yan; Zhang, Hai; Lv, Diya; Zhao, Yahong; Liu, Yanjun; Ye, Guan; Chai, Yifeng
• Is Part Of: Journal of ethnopharmacology. Volume 219(2018)
• Page Start: 359
• Page End: 368
• Publication Date: 2018-06-12
• Subjects: TCM Traditional Chinese medicine -- YXST Yangxinshi tablet -- SPR Surface plasmon resonance -- PPARγ Peroxisome proliferator-activated receptor gamma -- ACE Angiotensin-converting enzyme -- MAPK Mitogen-activated protein kinase 14 -- KEGG Kyoto Encyclopedia of Genes and Genomes -- RCSB Research Collaboratory for Structural Bioinformatics -- NCBI the National Center for Biotechnological Information -- GO Gene Ontology -- STRING Search Tool for the Retrieval of Interacting Genes/Proteins -- EDC 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride -- NHS N-hydroxysulfosuccinimide -- PBS phosphate-buffered saline -- HMGCR 3-hydroxy-3-methylglutaryl-coenzyme A -- TGF-β transforming growth factor β -- TNF-α tumor necrosis factor α -- IFN interferon -- ADBR1 β1 adrenergic receptor -- AGTR1 angiotensinⅡtype l receptor -- . UPLC-QTOF-MS -- JNK3 c-Jun N-terminal kinase 3 -- RAAS renin–angiotensin–aldosterone system -- HMG-CoA 3-hydroxy-3-methyl glutaryl coenzyme A -- Rmax The maximal expected binding level -- AMPK AMP-activated protein kinase -- PKG cGMP and protein kinase G; Yangxinshi tablet -- Network pharmacology -- Heart failure; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2017.12.011
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Yangxinshi tablet (YXST) is an effective treatment for heart failure and myocardial infarction; it consists of 13 herbal medicines formulated according to traditional Chinese Medicine (TCM) practices. It has been used for the treatment of cardiovascular disease for many years in China. Materials and methods: In this study, a network pharmacology-based strategy was used to elucidate the mechanism of action of YXST for the treatment of heart failure. Cardiovascular disease-related protein target and compound databases were constructed for YXST. A molecular docking platform was used to predict the protein targets of YXST. The affinity between proteins and ingredients was determined using surface plasmon resonance (SPR) assays. The action modes between targets and representative ingredients were calculated using Glide docking, and the related pathways were predicted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: A protein target database containing 924 proteins was constructed; 179 compounds in YXST were identified, and 48 compounds with high relevance to the proteins were defined as representative ingredients. Thirty-four protein targets of the 48 representative ingredients were analyzed and classified into two categories: immune and cardiovascular systems. The SPR assay and molecular docking partly validated the interplay between protein targets and representative ingredients. Moreover, 28 pathways related to heart failure were identified, which provided directions for further research on YXST. Conclusions: This study demonstrated that the cardiovascular protective effect of YXST mainly involved the immune and cardiovascular systems. Through the research strategy based on network pharmacology, we analysis the complex system of YXST and found 48 representative compounds, 34 proteins and 28 related pathways of YXST, which could help us understand the underlying mechanism of YSXT's anti-heart failure effect. The network-based investigation could help researchers simplify the complex system of YXSY. It may also offer a feasible approach to decipher the chemical and pharmacological bases of other TCM formulas. Graphical abstract: fx1