Abstract

Objective: To explore the mechanism of Shengmai Yin (SMY) for coronary heart disease (CHD) by systemic pharmacology and chemoinformatics.Methods: Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), traditional Chinese medicine integrative database (TCMID) and the traditional Chinese medicine (TCM) Database@Taiwan were used to screen and predict the bioactive components of SMY. Pharmmapper were utilized to predict the potential targets of SMY, the TCMSP was utilized to obtain the known targets of SMY. The Genecards and OMIM database were utilized to collect CHD genes. Cytoscape was then used for network construction and analysis, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. After that, animal experiments were then performed to further validate the results of systemic pharmacology and chemoinformatics.Results: Three major networks were constructed: (1) CHD genes’ protein–protein interaction (PPI) network; (2) SMY–CHD PPI network; (3) SMY known target–CHD PPI network. The other networks are minor networks generated by analyzing the three major networks. Experimental results showed that compared with the model group, the Shengmai injection (SMI) can reduce the myocardial injury score and the activities of serum aspartate aminoconvertase (AST), CK and lactate dehydrogenase (LDH) in rats (P<0.05), and reduce serum lipid peroxide (LPO) content and increase serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in myocardial infarction rats (P<0.05). SMI can also decrease the expression of MMP-9 mRNA and increase that of TIMP-1 mRNA (P<0.01).Conclusion: SMY may regulate the signaling pathways (such as PPAR, FoxO, VEGF signaling), biological processes (such as angiogenesis, blood pressure formation, inflammatory response) and targets (such as AKT1, EGFR, MAPK1) so as to play a therapeutic role in CHD.

Highlights

  • Coronary heart disease (CHD) is a heart disease caused by coronary atherosclerosis [1,2]

  • The CHD genes’ protein–protein interaction (PPI) network was constructed according to these information. This network consists of 247 CHD gene nodes and 4812 edges (Figure 1)

  • The topological property of this network was assessed by network analyzer tool, and the result demonstrates that Shengmai Yin (SMY)–CHD PPI network meets the power-law distribution (R2 = 0.665, y = 56.438x−0.739) (Figure 8), indicating that this is scale-free and has the general characteristic of biological network

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Summary

Introduction

Coronary heart disease (CHD) is a heart disease caused by coronary atherosclerosis [1,2]. In China, patients with CHD increase at an annual rate of 20%, and the number of deaths is approximately 10–20% of all heart diseases. The Western medicine treatment of CHD is mainly based on comprehensive management. According to the patient’s disease stage, the treatment is mainly based on anti-platelet, anti-atherosclerosis and lipid-lowering stable plaques [5,6]. In alternative medicine, traditional Chinese medicine (TCM) has gradually shown its unique advantages in the treatment of CHD. With the increase in the number of large-scale randomized controlled trials, the Chinese medicine formula has gradually become the first-line treatment measure for CHD treatment [7,8,9]. Tongxinluo Capsule and Fufang Danshen Diwan can achieve a certain effect in the treatment of CHD [8,9]

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