Exploring the Therapeutic Mechanisms of Huzhang–Shanzha Herb Pair against Coronary Heart Disease by Network Pharmacology and Molecular Docking

Background. Coronary heart disease (CHD) seriously affects human health, and its pathogenesis is closely related to atherosclerosis. The Huzhang (the root of Polygonum cuspidatum)–Shanzha (the fruit of Crataegus sp.), a classic herb pair, has been widely used for the treatment of CHD. In recent years, Huzhang–Shanzha herb pair (HSHP) was found to have a wide range of effects in CHD; however, its therapeutic specific mechanisms remain to be further explored. The aim of this study was to elucidate the molecular mechanism of HSHP in the treatment of CHD using a network pharmacology analysis approach. Methods. The Batman-TCM database was used to explore bioactive compounds and corresponding targets of HSHP. CHD disease targets were extracted from Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Then, the protein-protein interaction (PPI) network was constructed using the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Finally, molecular docking of the active components was assessed to verify the potential targets of HSHP to treat CHD by the AutoDock Vina and PyMOL software. Results. Totally, 243 active components and 2459 corresponding targets of LDP were screened out. Eighty-five common targets of HSHP and CHD were identified. The results of the network analysis showed that resveratrol, anthranone, emodin, and ursolic acid could be defined as four therapeutic components. TNF, ESR1, NFКB1, PPARG, INS, TP53, NFКBIA, AR, PIK3R1, PIK3CA, PTGS2, and NR3C1 might be the 12 key targets. These targets were mainly involved in the regulation of biological processes, such as inflammatory responses and lipid metabolism. Enrichment analysis showed that the identified genes were mainly involved in fluid shear force, insulin resistance (IR), inflammation, and lipid metabolism pathways to contribute to CHD. This suggests that resveratrol, anthranone, emodin, and ursolic acid from HSHP can be the main therapeutic components of atherosclerosis. Conclusion. Using network pharmacology, we provide new clues on the potential mechanism of action of HSHP in the treatment of CHD, which may be closely related to the fluid shear force, lipid metabolism, and inflammatory response.

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A network pharmacology approach to reveal the protective mechanism of Salvia miltiorrhiza-Dalbergia odorifera coupled-herbs on coronary heart disease

Scientific Reports ◽

10.1038/s41598-019-56050-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Fei Li ◽

Jialin Duan ◽

Meina Zhao ◽

Shaojie Huang ◽

Fei Mu ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Lipid Metabolism ◽

Endothelial Function ◽

Salvia Miltiorrhiza ◽

Network Pharmacology ◽

Vascular Endothelial ◽

Bioactive Components ◽

Vascular Endothelial Function ◽

Dalbergia Odorifera

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.

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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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The Active Compounds of Yixin Ningshen Tablet and Their Potential Action Mechanism in Treating Coronary Heart Disease- A Network Pharmacology and Proteomics Approach

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4912395 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Xing Lv ◽

Huijun Wang ◽

Ruoming Wu ◽

Xiaoyan Shen ◽

Guan Ye

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Endocrine Resistance ◽

Arachidonic Acid Metabolism ◽

Network Pharmacology ◽

Active Components ◽

Literature Study ◽

Active Compounds ◽

Target Proteins ◽

Potential Target

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.

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Molecular Mechanism of Danxiong Tongmai Granules in Treatment of Coronary Heart Disease

10.21203/rs.3.rs-784340/v1 ◽

2021 ◽

Author(s):

Jiahao Ye ◽

Ruiping Yang ◽

Zhixi Hu ◽

Lin Li ◽

Senjie Zhong ◽

...

Keyword(s):

Molecular Dynamics ◽

Coronary Heart Disease ◽

Heart Disease ◽

Molecular Docking ◽

Enrichment Analysis ◽

Dynamics Simulation ◽

Venn Diagram ◽

Network Pharmacology ◽

Ppi Network ◽

Ligand Interaction

Abstract Background: Network pharmacology has been widely adopted for mechanistic studies of Traditional Chinese Medicines (TCM). The present study uses network pharmacology to investigate the main ingredients, targets and pathways of Danxiong Tongmai Granules (DXTMG) in the treatment of coronary heart disease (CHD). We aim to validate our findings using molecular docking and molecular dynamics simulations.Methods: TCM compounds and targets were identified via searches in the BATMAN-TCM database, and the GeneCards database were used to obtain the main target genes involved in CHD, We combined disease targets with the drug targets to identify common targets, and draw a Venn diagram to visualize the results. The "TCM-compound-target" network was plotted using Cytoscape 3.7.2 software and a protein-protein interaction (PPI) network was constructed using the STRING database from which core targets were obtained. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for common drug-disease targets using R Version 4.0.4 (64 bit) software. Molecular docking of core protein-small molecule ligand interaction was modeled using AutoDock Vina software. A simulation of molecular dynamics was conducted for the optimal protein-ligand complex obtained by molecular docking using Amber18 software.Results: 162 potential targets of DXTMG involved in CHD were identified. These included INS, ALB, IL-6 and TNF according to PPI network studies. GO enrichment analysis identified a total of 3365 GO pathways, including 3049 biological process pathways (BP) concerned with the heart and circulatory system;109 cellular component (CC) pathways, including cation channels and membrane rafts and 207 molecular function (MF) pathways related to receptor ligands and activators. KEGG analysis revealed a total of 137 pathways (p<0.05), including those related to AGE-RAGE signaling associated with diabetic complications, fluid shear stress and atherosclerosis. Molecular docking revealed the highest binding energy for Neocryptotanshinone Ii (the key compound of DXTMG) and TNF. Molecular dynamics simulation indicated stable binding for TNF-Neocryptotanshinone Ii with strong hydrophobic interactions mediated predominantly by the hydrophobic residues, Leu279, Val280 and Phe278 plus hydrogen-bonding with Leu279.Conclusion: The present study reveals novel insights into the mechanism of DXTMG in treating CHD. DXTMG can influence oxidative stress、inflammation response and regulating cardiomyocytes, thereby reducing the occurrence and development of CHD.

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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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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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Mechanism of Baihe Decoction in the treatment of coronary heart disease based on network pharmacology and molecular docking

Annals of Palliative Medicine ◽

10.21037/apm-21-543 ◽

2021 ◽

Vol 10 (3) ◽

pp. 3205-3218

Author(s):

Yaxian Jin ◽

Xiaodan Yin ◽

Zhenying Li ◽

Jiangyan Xu

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Molecular Docking ◽

Network Pharmacology

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Exploring the Molecular Mechanism of Liuwei Dihuang Pills for Treating Diabetic Nephropathy by Combined Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/7262208 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Gaoxiang Wang ◽

Lin Zeng ◽

Qian Huang ◽

Zhaoqi Lu ◽

Ruiqing Sui ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Molecular Docking ◽

Enrichment Analysis ◽

Underlying Mechanism ◽

Network Pharmacology ◽

Signal Pathways ◽

Active Components ◽

Active Compounds ◽

Liuwei Dihuang Pills ◽

Web Platform

Background. Diabetic nephropathy (DN) is a common and serious complication of diabetes, but without a satisfactory treatment strategy till now. Liuwei Dihuang pills (LDP), an effective Chinese medicinal formula, has been used to treat DN for more than 1000 years. However, its underlying mechanism of action is still vague. Methods. Active compounds and corresponding targets of LDP were predicted from the TCMSP database. DN disease targets were extracted from the OMIM, GeneCards, TTD, DisGeNET, and DrugBank databases. Subsequently, the “herbal-compound-target” network and protein-protein interaction (PPI) network were constructed and analyzed via the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Molecular docking utilized AutoDock Vina and PyMOL software. Results. 41 active components and 186 corresponding targets of LDP were screened out. 131 common targets of LDP and DN were acquired. Quercetin, kaempferol, beta-sitosterol, diosgenin, and stigmasterol could be defined as five crucial compounds. JUN, MAPK8, AKT1, EGF, TP53, VEGFA, MMP9, MAPK1, and TNF might be the nine key targets. The enrichment analysis showed that common targets were mainly associated with inflammation reaction, oxidative stress, immune regulation, and cell apoptosis. AGE-RAGE and IL-17 were the suggested two significant signal pathways. Molecular docking revealed that the nine key targets could closely bind to their corresponding active compounds. Conclusion. The present study fully reveals the multicompound’s and multitarget’s characteristics of LDP in DN treatment. Furthermore, this study provides valuable evidence for further scientific research of the pharmacological mechanisms and broader clinical application.

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