Abstract
Yixin Ningshen tablet is a CFDA-approved TCM formula for treating coronary heart disease (CHD) clinically. However, its active compounds and mechanism of action in treating CHD are unknown. In this study, a novel strategy with the combination of network pharmacology and proteomics was proposed to identify the active components of Yixin Ningshen tablet and the mechanism by which they treat CHD. With the application of network pharmacology, 62 active compounds in Yixin Ningshen tablet were screened out by text mining, and their 313 potential target proteins were identified by a tool in SwissTargetPrediction. These data were integrated with known CHD-related proteomics results to predict the most possible targets, which reduced the 313 potential target proteins to 218. The STRING database was retrieved to find the enriched pathways and related diseases of these target proteins, which indicated that the Calcium, MAPK, PI3K-Akt, cAMP, Rap1, AGE-RAGE, Relaxin, HIF-1, Prolactin, Sphingolipid, Estrogen, IL-17, Jak-STAT signaling pathway, necroptosis, arachidonic acid metabolism, insulin resistance, endocrine resistance, and steroid hormone biosynthesis might be the main pathways regulated by Yixin Ningshen tablet for the treatment of CHD. Through further enrichment analysis and literature study, EGFR, ERBB2, VGFR2, FGF1, ESR1, LOX15, PGH2, HMDH, ADRB1, and ADRB2 were selected and then validated to be the target proteins of Yixin Ningshen tablet by molecular docking, which indicated that Yixin Ningshen tablet might treat CHD mainly through promoting heart regeneration, new vessels' formation, and the blood supply of the myocardial region and reducing cardiac output, oxygen demand, and inflammation as well as arteriosclerosis (promoting vasodilation and intraplaque neoangiogenesis, lowering blood lipid). This study is expected to benefit the clinical application of Yixin Ningshen tablet for the treatment of CHD.
Highlights
CHD, with clinical condition presented as angina, myocardial infarction, sudden death, and consequent chronic heart failure, is the leading cause of death in noncommunicable diseases and accounted for about 1/3 of all deaths worldwide (17.5 million) in 2012 [1, 2]
Database Construction. e compound information present in Yixin Ningshen tablet was obtained from the TCM Database @ Taiwan [12], Traditional Chinese Medicines Integrated Database [13], and Chemistry Database. e active compounds of Wu Wei Zi, Ren Shen, He Huan Hua, and Ling Zhi were identified by text mining from the National Center of Biotechnology Information PubMed database. e search bar was composed of a compound name in Yixin Ningshen Tablet and heart or cardiac or myocardial
Text mining was firstly applied to identify 62 components in Yixin Ningshen tablet with cardioprotective activity. en, 313 potential targets of these compounds were predicted by SwissTargetPrediction
Summary
CHD, with clinical condition presented as angina, myocardial infarction, sudden death, and consequent chronic heart failure, is the leading cause of death in noncommunicable diseases and accounted for about 1/3 of all deaths worldwide (17.5 million) in 2012 [1, 2]. Clinical research demonstrated that CHD is an end-stage disease originating from longstanding subclinical atheroma; treatments need to be well designed based on its different stages of pathogenesis [1]. Most researchers have designed new drugs for CHD based on the “one drug for one target for one disease” assumption [3, 4]. En, the combination therapy with multiple drugs is always applied clinically, which could cause adverse off-target effects and adverse drug interactions. Safer and more effective treatment strategies for CHD are in urgent need
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