scholarly journals A Network Pharmacology Analysis to Reveal the Molecular Mechanism of Zhizi-Danshen on Coronary Heart Disease

2020 ◽  
Author(s):  
Yue-hong Shen ◽  
Shu-lin Wang ◽  
Na Wu ◽  
Yu-chen Dai ◽  
Qian Zhou ◽  
...  

Abstract ObjectiveOur study aimed to investigate the potential mechanisms of the herb pair Zhizi-Danshen (ZD) for coronary heart disease (CHD) using network pharmacological data mining technology.MethodsThe Traditional Chinese Medicine System Pharmacology (TCMSP) database was used to collect the active ingredients of ZD and predict ZD-related target proteins. Afterwards, we identified CHD-related targets from DisGeNET database, NCBI gene database, and TTD database. The common targets both from ZD and CHD were screened by Venny2.1, which were then imported into the String database for protein-protein interaction (PPI) analysis. Finally, the GO and KEGG enrichment analysis were performed by R software, and the network construction was established using Cytoscape3.7.2.ResultsWe obtained 199 possible targets from 62 candidate ingredients of ZD and 1033 CHD-ralated targets, with 83 overlapping common target genes. Then, 11 core targets were acquired from PPI network analysis. Further, GO analysis showed that these common targets mainly influenced receptor ligand activity,cytokine activity,cytokine receptor binding,steroid hormone receptor activity, and peptide binding. KEGG pathway analysis indicated that ZD affected CHD through seven important pathways linked to vascular endothelial function regulation (fluid shear stress and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway), imflammatory effects (IL-17 signaling pathway, TNF signaling pathway,Toll-like receptor signaling pathway),and hormone regulation (relaxin signaling pathway). ConclusionsThis study revealed the potential pharmacological mechanisms of ZD against CHD, which were mainly associated with regulation of vascular endothelial function and inflammatory effects, promotion of vasodilatation, and prevention of cardiac fibrosis. Moreover, it provided a novel conception for the development of alternative therapies on CHD.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fei Li ◽  
Jialin Duan ◽  
Meina Zhao ◽  
Shaojie Huang ◽  
Fei Mu ◽  
...  

AbstractSalvia miltiorrhiza-Dalbergia odorifera coupled-herbs (SMDOCH) has been used to treat coronary heart disease (CHD) for thousands of years, but its unclear bioactive components and mechanisms greatly limit its clinical application. In this study, for the first time, we used network pharmacology to elucidate the mechanisms of action of SMDOCH on CHD. We collected 270 SMDOCH-related targets from 74 bioactive components and 375 CHD-related targets, with 58 overlapping common targets. Next, we performed enrichment analysis for common-target network and protein-protein interaction (PPI) network. The results showed that SMDOCH affected CHD mainly through 10 significant signaling pathways in three biological processes: ‘vascular endothelial function regulation’, ‘inflammatory response’, and ‘lipid metabolism’. Six pathways belonged to the ‘vascular endothelial function regulation’ model, which primarily regulated hormone (renin, angiotensin, oestrogen) activity, and included three key upstream pathways that influence vascular endothelial function, namely KEGG:04933, KEGG:05418, and KEGG:04066. Three pathways, namely KEGG:04668, KEGG:04064, and KEGG:04620, belonged to the ‘inflammatory response’ model. One pathway (KEGG:04920) belonged to the ‘lipid metabolism’ model. To some extent, this study revealed the potential bioactive components and pharmacological mechanisms of SMDOCH on CHD, and provided a new direction for the development of new drugs for the treatment of CHD.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Cailan Li ◽  
Qian Li ◽  
Jiamin Xu ◽  
Wenzhen Wu ◽  
Yuling Wu ◽  
...  

Objective. Compound Danshen dripping pill (CDDP) is a well-known Chinese patent medicine, which is commonly used for the treatment of coronary heart disease (CHD) in China. This study is aimed at systematically assessing the clinical efficacy of CDDP for CHD patients. Methods. Eight databases were retrieved for eligible research studies from the founding date to April 20, 2020. Risk ratio (RR) was used to assess major adverse cardiac events (MACE) and adverse reactions, and mean difference (MD) was adopted to evaluate the hemorheology and blood lipid indexes, vascular endothelial function, cardiac function, and inflammation. Result. Twenty randomized controlled trials involving 2574 participants with CHD were included. The results indicated that, compared with percutaneous coronary intervention (PCI) alone, the combination of CDDP with PCI treatment remarkably reduced MACE (RR = 0.53, 95% confidence interval (CI) (0.44, 0.65), P < 0.00001 ). Moreover, hemorheology and blood lipid parameters and inflammatory mediators of CHD patients were also dramatically mitigated after the combined therapy P < 0.01 . In addition, vascular endothelial function and cardiac function were prominently improved by this combination P < 0.001 . However, there was no significant difference in adverse reactions between the two groups P > 0.05 . Conclusion. Evidence from the meta-analysis demonstrated that CDDP combined with PCI treatment prominently reduced the incidence of MACE, improved cardiovascular functions, and inhibited inflammation in CHD patients. Therefore, CDDP combined with PCI treatment could be an effective and safe therapeutic method for CHD patients.


2013 ◽  
Vol 25 (2) ◽  
pp. 222-227 ◽  
Author(s):  
Mohammad Reza Sabri ◽  
Hooman Daryoushi ◽  
Mojgan Gharipour

AbstractBackgroundRepairing cyanotic congenital heart disease may be associated with preserving endothelial function. The present study aimed to evaluate vascular endothelial function in patients with repaired cyanotic congenital heart disease.MethodsIn a case–control study conducted in 2012 in Isfahan, Iran, 42 consecutive patients aged <35 years who had suffered from different types of cyanotic congenital heart disease and had undergone complete repair of their congenital heart defect were assessed in regard to their endothelial function state by measuring flow-mediated dilatation and other cardiac function indices. They were paired with 42 sex- and age-matched healthy controls.ResultsThe mean flow-mediated dilatation was lower in patients with repaired cyanotic congenital heart disease than in the controls [6.14±2.78 versus 8.16±1.49 respectively (p<0.001)]. Significant adverse correlations were found between flow-mediated dilatation, age, and body mass indexes, in those who underwent repair surgery. In addition, flow-mediated dilatation had a positive association with the shortening fraction, ejection fraction, and tricuspid annular plane systolic excursion value, and it was also inversely associated with carotid intima-media thickness and the myocardial performance index. The mean of the flow-mediated dilatation was significantly higher in the group with tetralogy of Fallot along with complete repair before the age of 2.5 years and also in those patients with total anomalous pulmonary venous connection or transposition of the great arteries repaired with an arterial switch operation before 6 months of age, compared with the other two subgroups. This includes patients with a tetralogy of Fallot defect repaired after 4 years of age and those with complex cyanotic congenital heart disease that was repaired after 2.5 years of age (mean age at repair 9±6.1 years).ConclusionEarly repair of a cyanotic defect can result in the protection of vascular endothelial function and prevent the occurrence of vascular accidents at an older age.


2021 ◽  
Vol 12 ◽  
Author(s):  
Li-ying Jia ◽  
Gui-yun Cao ◽  
Jia Li ◽  
Lu Gan ◽  
Jin-xin Li ◽  
...  

SheXiang XinTongNing (XTN), which is composed of six traditional Chinese herbs, is a commercially available Chinese patent medicine that has been widely used as the treatment of coronary heart disease (CHD). Its mechanisms against coronary heart disease, however, remain largely unknown. This study aimed to investigate the pharmacological mechanisms of XTN against CHD via network pharmacology and experimental evaluation. In this study, GO enrichment and KEGG pathway enrichment were firstly performed for acquiring the potentially active constituents of XTN, the candidate targets related to coronary heart disease, the drug-components-targets network as well as the protein-protein interaction network and further predicting the mechanisms of XTN against coronary heart disease. Subsequently, a series of in vitro experiments, specifically MTT assay, flow cytometry and Real-time quantitative polymerase chain reaction analysis, and a succession of in vivo experiments, including Tunel staining and immunohistochemical staining were conducted for further verification. Results showed that Bcl-2, IGF1, CASP3 were the key candidate targets which significantly associated with multiple pathways, namely PI3K-Akt signaling pathway and MAPK signaling pathway. It indicated that the potential mechanism of XTN against CHD may be predominantly associated with cell apoptosis. The in vitro experimental results showed that XTN treatment remarkably decreased the apoptotic rate and Bax/Bcl-2 ratio of H9c2 cells. Histological results confirmed that XTN not only effectively alleviated oxidative damage caused by myocardial ischemia but inhibited cell apoptosis. Given the above, through the combined utilization of virtual screening and experimental verification, the findings suggest that XTN makes a significant contribution in protecting the heart from oxidative stress via regulating apoptosis pathways, which lays the foundations and offers an innovative idea for future research.


2020 ◽  
Author(s):  
Ying Li ◽  
Guhang Wei ◽  
Zhenkun Zhuang ◽  
Mingtai Chen ◽  
Changjian Yuan ◽  
...  

Abstract BackgroundCorydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used.Materials and MethodsThe active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform.Results49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway.ConclusionsOverall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.


2020 ◽  
Author(s):  
Ying Li ◽  
Guhang Wei ◽  
Zhenkun Zhuang ◽  
Mingtai Chen ◽  
Haidan Lin ◽  
...  

Abstract Background. Corydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used. Materials and Methods. The active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform. Results. 49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway. Conclusions. Overall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.


2020 ◽  
Author(s):  
Li-ying Jia ◽  
Jia Li ◽  
Gui-yun Cao ◽  
Zhao-qing Meng ◽  
Lu Gan ◽  
...  

Abstract Background SheXiang XinTongNing, a commercially available Chinese patent medicine, has been widely used in the treatment of coronary heart disease. However, the mechanisms of SheXiang XinTongNing are still unclear. The aim of this study was to investigate the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease via network analysis. Method The traditional Chinese medicine system pharmacology analysis platform was used to screen the potential active constituents of the six traditional Chinese medicines in SheXiang XinTongNing, and the potential targets were obtained from PharmMapper. The genome annotation database platform was used to screen the candidate targets related to coronary heart disease. Then the drug-components-targets network and protein interaction network were built by Cytoscape 3.6.0 software. Further, GO bio-functional enrichment analysis and KEGG pathway enrichment analysis were performed through annotation, visualization and integrated discovery database. Results Results showed that the drugs-components-targets network contains 104 targets and 62 key components. The protein interaction network consisted of 107 nodes; key targets included Bcl2l1, IGF1, SRC, CASP3, et al. Functionally, the candidate targets were significantly associated with multiple pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway, Endocrine resistance. Given the above, the pharmacological activities of SheXiang XinTongNing may be predominantly related to several factors such as cell apoptosis, inflammation and angiogenesis. Conclusion XTN can effectively attenuate the symptoms of coronary heart disease through diverse pathways. The research proves that network pharmacology can successfully reveal the mechanisms of traditional Chinese medicine in a holistic view. Our systematic analysis lays a foundation for further studying.


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