Effect of Ginsenoside Rb2 on a Myocardial Cell Model of Coronary Heart Disease through Nrf2/HO-1 Signaling Pathway

In this paper, by examining the toxicity of nano-silica to coronary heart disease cells, we explored the apoptosis of rat myocardial cells induced by nano-silica, and explored the effect of apoptosis on cells during the process of myocardial cytotoxicity induced by nano-silica. This article selects rat cardiomyocytes as the research object and conducts a group control experiment. A control group is set up with cells that are not stained with nano-silica. Different concentrations of nanosilica suspensions are applied to rat cells and detected by CCK-8 method. Cell survival rate after exposure to different concentrations of cells is used to determine the most stable exposure time and concentration. We used flow cytometry to detect intracellular reactive oxygen species and apoptotic rates, and used Western Blot to detect the expression of proteins that affect apoptosis. Finally, we investigated the effect of the Wnt signaling pathway on coronary heart disease. The Wnt signaling pathway regulates the development of the heart and blood vessels. In the treatment of cardiovascular disease, this pathway will be activated again to play a regulatory role. We conclude that nano-silica can induce cytotoxicity in rat myocardial cells through the Wnt-1 pathway, and nanosilica can induce myocardial cell apoptosis through the Wnt-1 pathway.

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

10.21203/rs.3.rs-85979/v1 ◽

2020 ◽

Author(s):

Yue-hong Shen ◽

Shu-lin Wang ◽

Na Wu ◽

Yu-chen Dai ◽

Qian Zhou ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Endothelial Function ◽

Signaling Pathway ◽

Target Genes ◽

Cardiac Fibrosis ◽

Fluid Shear Stress ◽

Network Pharmacology ◽

Vascular Endothelial ◽

Vascular Endothelial Function

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.

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Dependence of the content of individual molecules in agranucocytes of whole blood at coronary heart disease from the level of phosphorylation of protein kinase r 38 in terms of low intensity microwave radiation

Journal of New Medical Technologies eJournal ◽

10.12737/18561 ◽

2016 ◽

Vol 10 (1) ◽

pp. 0-0 ◽

Cited By ~ 1

Author(s):

Логаткина ◽

A. Logatkina ◽

Бондарь ◽

S. Bondar ◽

Терехов ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Protein Kinase ◽

Signaling Pathway ◽

Microwave Radiation ◽

Whole Blood ◽

Mononuclear Cells ◽

Protein Kinase R ◽

Low Intensity ◽

Mononuclear Leucocytes

Molecular indicators reflecting the states of stress-limiting systems of mononuclear leucocytes in the blood, as well as the effects of low-intensive microwave radiation in patients with coronary artery disease were studied. The work it was evaluated the content in mononuclear leucocytes whole blood of components PI3P/AKT/mTOR/p70S6K1 of signaling pathway, heat shock proteins (HSP27, HSP70, HSP90), the concentra-tion of antioxidants and peroxides depending on the level of phosphorylation of the terminal protein kinase MAPK/SAPK of signaling pathway – p38. The results of the study. It was revealed the dependence of a level of studied factors from the degree of phosphorylation p38 in patients with coronary heart disease. It was defined the 38 p sensitivity to the effects of low-intensity microwave radiation, it is manifested by increased level of phosphorylation in the irradiated cul-tures. This study revealed the sensitivity to low-intensity microwave irradiation of content in the mononuclear cells phosphorylated forms of the protein kinases AMPK, AKT1, p70S6K1, as well as the antioxidant status and protein of p53-dependent initial content in the cell phosphorylated form p38. It was shown a possibility of microwave radiation to reduce the content in the cells of the protein kinase and p70 ACT more pronounced at high levels of phosphorylation p38.

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Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.698981 ◽

2021 ◽

Vol 12 ◽

Author(s):

Li-ying Jia ◽

Gui-yun Cao ◽

Jia Li ◽

Lu Gan ◽

Jin-xin Li ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Experimental Evaluation ◽

Mapk Signaling ◽

Chinese Herbs ◽

Network Pharmacology ◽

Tunel Staining

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.

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A Network Pharmacology-Based Study on Active Ingredients of Corydalis Rhizoma on Coronary Heart Disease

10.21203/rs.3.rs-90765/v1 ◽

2020 ◽

Author(s):

Ying Li ◽

Guhang Wei ◽

Zhenkun Zhuang ◽

Mingtai Chen ◽

Changjian Yuan ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Signaling Pathway ◽

Network Pharmacology ◽

Active Ingredients ◽

Active Components

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.

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Decoy receptor‑3 regulates inflammation and apoptosis via PI3K/AKT signaling pathway in coronary heart disease

Experimental and Therapeutic Medicine ◽

10.3892/etm.2019.7222 ◽

2019 ◽

Cited By ~ 2

Author(s):

Xinjing Chen ◽

Rehua Wang ◽

Wei Chen ◽

Li Lai ◽

Zhiliang Li

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Decoy Receptor ◽

Decoy Receptor 3

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The Protective Effects of miR-21-Mediated Fibroblast Growth Factor 1 in Rats with Coronary Heart Disease

BioMed Research International ◽

10.1155/2021/3621259 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Bin Zhang ◽

Hongguang Liu ◽

Guoping Yang ◽

Yongmei Wang ◽

Yan Wang

Keyword(s):

Blood Pressure ◽

Coronary Heart Disease ◽

Heart Disease ◽

Growth Factor ◽

Myocardial Ischemia ◽

Fibroblast Growth Factor ◽

Myocardial Cell ◽

Protective Effects ◽

Fibroblast Growth ◽

Myocardial Cells

Aim. The study is to verify the protective effects of miR-21-mediated fibroblast growth factor 1 (FGF1) against myocardial ischemia in rats with coronary heart disease. Materials and Methods. Sprague-Dawley (SD) rat models of myocardial ischemia/reperfusion (MI/R) injury were constructed, and the expression of miR-21 and FGF1 in them was interfered through ischemic postconditioning. The protective effects of miR-21-mediated FGF1 on myocardium of the model rats were analyzed, and the targeted regulatory relationship between miR-21 and FGF1 was verified through myocardial cell experiments to find the mechanism of miR-21. Results. MiR-21 and FGF1 with increased expression could protect the cardiac function of model rats and improve their diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR), coronary flow (CF), bax, and bcl-2 levels, but it would also cause further increase of vascular endothelial growth factor (VEGF) and decreased infarct size (INF). In addition, intervention through both miR-21 mimics and recombinant human FGF1 could highlight the above changes. Pearson correlation analysis revealed that the expression of miR-21 was positively correlated with that of FGF1, and both miR-21 and FGF1 were significantly and linearly correlated with DBP, SBP, HR, CF, INF, bax, and bcl-2, but they were not significantly correlated with the VEGF level. The myocardial cell experiment results revealed that upregulation of miR-21 or FGF1 could alleviate apoptosis caused by hypoxia/reoxygenation of myocardial cells, and inhibition of the FGF1 expression could hinder the effect of miR-21 against apoptosis of myocardial cells. Dual luciferase reporter assay revealed that transfection of miR-21-mimics could effectively raise the fluorescence intensity of pmirGLO-FGF1-3 ′ UTR Wt but had no significant effect on that of pmirGLO-FGF1-3 ′ UTR Mut. Conclusion. MiR-21 can specifically mediate the expression of FGF1 to relieve MI/R injury, protect the cardiac function, and resist apoptosis.

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A Network Pharmacology-Based Study on Active Ingredients of Corydalis Rhizoma on Coronary Heart Disease

10.21203/rs.3.rs-41449/v1 ◽

2020 ◽

Author(s):

Ying Li ◽

Guhang Wei ◽

Zhenkun Zhuang ◽

Mingtai Chen ◽

Haidan Lin ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Signaling Pathway ◽

Network Pharmacology ◽

Active Ingredients ◽

Active Components

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.

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Investigating the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease based on network pharmacology

10.21203/rs.3.rs-21814/v1 ◽

2020 ◽

Author(s):

Li-ying Jia ◽

Jia Li ◽

Gui-yun Cao ◽

Zhao-qing Meng ◽

Lu Gan ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Protein Interaction ◽

Protein Interaction Network ◽

Interaction Network ◽

Enrichment Analysis ◽

Network Pharmacology

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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A Multi-Scale Bioinformatics Study on Novel Mechanism of Xintong Granule for Treating Coronary Heart Disease by Network Pharmacology and Molecular Docking Verification

10.21203/rs.3.rs-116130/v1 ◽

2020 ◽

Author(s):

Zhihong Huang ◽

Siyu Guo ◽

Changgeng Fu ◽

Wei Zhou ◽

Jingyuan Zhang ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Chinese Herbs ◽

Network Pharmacology ◽

Pharmacological Mechanism ◽

Vascular Regulation

Abstract Background: Xintong Granule (XTG) is a Chinese patent medicine composed of 13 Chinese herbs, which is widely used in the treatment of coronary heart disease (CHD). However, there are few studies on it, and its potential pharmacological mechanism needs to be further elucidated.Methods: In this study, network pharmacology was employed to construct the drug-compounds-targets-pathways molecular regulatory network of the treatment of CHD to explore the effective compounds of XTG and its underlying pharmacological mechanism. First, we established the related ingredients and potential targets of these ingredients databases by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and A Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM). Next, the CHD targets were obtained in DigSee, OMIM, DisGeNET, TTD, GeneCards and GenCLiP3 database. Then, protein-protein interaction (PPI) analysis, GO and KEGG pathway enrichment analysis were carried out and the core targets were filtered by topology. Moreover, molecular docking was performed to assess the binding potential of hub targets and key compounds.Results: The result reflected that 178 components of XTG and 669 putative therapeutic targets were screened out. After a systematic and comprehensive analysis, we identified 9 hub targets (TNF, MAPK1, STAT3, IL6, AKT1, INS, EGFR, EGF, TP53) primarily participated in the comprehensive therapeutic effect related to blood circulation, vascular regulation, cell membrane region, compound binding, receptor activity, signal transduction, AGE-RAGE signaling pathway in diabetic complications, JAK-STAT signaling pathway, PI3K-AKT signaling pathway and MAPK signaling pathway.Conclusion: The results of this study tentatively clarified the potential targets and signaling pathways of XTG against CHD, which may benefit to the development of clinical experimental research and application.

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