Cargando…

Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking

This study aimed to explore the mechanism of Yangxin Tongmai decoction (YXTMD) in the treatment of coronary heart disease (CHD) with blood stasis syndrome (BSS) using network pharmacology and molecular docking, and to verify these results through clinical trials. The active compounds of YXTMD were i...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Mengxue, Liu, Jia, Zhang, Xiangzhuo, Zhang, Shumeng, Jiang, Yujie, Yu, Zixuan, Xie, Ting, Chen, Yuxia, Chen, Lingli, Li, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546682/
https://www.ncbi.nlm.nih.gov/pubmed/36212940
http://dx.doi.org/10.1155/2022/4692217
_version_ 1784805097394405376
author Zhang, Mengxue
Liu, Jia
Zhang, Xiangzhuo
Zhang, Shumeng
Jiang, Yujie
Yu, Zixuan
Xie, Ting
Chen, Yuxia
Chen, Lingli
Li, Jie
author_facet Zhang, Mengxue
Liu, Jia
Zhang, Xiangzhuo
Zhang, Shumeng
Jiang, Yujie
Yu, Zixuan
Xie, Ting
Chen, Yuxia
Chen, Lingli
Li, Jie
author_sort Zhang, Mengxue
collection PubMed
description This study aimed to explore the mechanism of Yangxin Tongmai decoction (YXTMD) in the treatment of coronary heart disease (CHD) with blood stasis syndrome (BSS) using network pharmacology and molecular docking, and to verify these results through clinical trials. The active compounds of YXTMD were identified using the Traditional Chinese Medicine Systems Pharmacology database, and the targets of the active compounds were predicted using the SwissTarget Prediction database. The targets of CHD and BSS were predicted using the GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases. The common targets of “herb-disease-phenotype” were obtained using a Venn diagram, then used Cytoscape software 3.8.2 and its plug-in CytoNCA and STRING database to construct the “herb active compounds-common target” and protein–protein interaction networks. R language software and bioconductor plug-in were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. AutoDock was used for the molecular docking analysis. Finally, clinical trials were conducted to confirm the results of network pharmacology. Eighty-three active components were obtained, and the core active components were 5,7,4′-trimethoxyflavone, tetramethoxyluteolin, isosinensetin, sinensetin, and 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one. A total of 140 common targets were identified, and the core targets were EGFR, VEGFA, AKT1, STAT3, TP53, ERBB2, and PIK3CA. Biological processes identified by the GO analysis primarily involved wound healing, regulation of body fluid levels, and vascular process in circulatory system. The cellular components were primarily located in the membrane raft, membrane microdomain, and plasma membrane raft. The primary molecular functions were activity of transmembrane receptor protein kinase, transmembrane receptor protein tyrosine kinase, and protein tyrosine kinase. KEGG analysis showed that the PI3K-Akt signaling pathway was closely related to the treatment of CHD with BSS by YXTMD. Molecular docking results showed that the core active components had a good binding activity with the core targets. The clinical trial results showed that YXTMD improved the BSS scores and decreased the serum levels of total cholesterol and low-density lipoprotein cholesterol. Moreover, the levels of PI3k and AKt mRNA were upregulated and the levels of GSK-3β mRNA were downregulated. YXTMD has multicomponent, multitarget, and multipathway effects in the treatment of CHD with BSS, and its mechanism of action may involve activation of the PI3K-AKt signaling pathway, downregulation of GSK-3β, and mediation of in vivo lipid metabolism-based metabolic processes.
format Online
Article
Text
id pubmed-9546682
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-95466822022-10-08 Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking Zhang, Mengxue Liu, Jia Zhang, Xiangzhuo Zhang, Shumeng Jiang, Yujie Yu, Zixuan Xie, Ting Chen, Yuxia Chen, Lingli Li, Jie Evid Based Complement Alternat Med Research Article This study aimed to explore the mechanism of Yangxin Tongmai decoction (YXTMD) in the treatment of coronary heart disease (CHD) with blood stasis syndrome (BSS) using network pharmacology and molecular docking, and to verify these results through clinical trials. The active compounds of YXTMD were identified using the Traditional Chinese Medicine Systems Pharmacology database, and the targets of the active compounds were predicted using the SwissTarget Prediction database. The targets of CHD and BSS were predicted using the GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases. The common targets of “herb-disease-phenotype” were obtained using a Venn diagram, then used Cytoscape software 3.8.2 and its plug-in CytoNCA and STRING database to construct the “herb active compounds-common target” and protein–protein interaction networks. R language software and bioconductor plug-in were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. AutoDock was used for the molecular docking analysis. Finally, clinical trials were conducted to confirm the results of network pharmacology. Eighty-three active components were obtained, and the core active components were 5,7,4′-trimethoxyflavone, tetramethoxyluteolin, isosinensetin, sinensetin, and 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one. A total of 140 common targets were identified, and the core targets were EGFR, VEGFA, AKT1, STAT3, TP53, ERBB2, and PIK3CA. Biological processes identified by the GO analysis primarily involved wound healing, regulation of body fluid levels, and vascular process in circulatory system. The cellular components were primarily located in the membrane raft, membrane microdomain, and plasma membrane raft. The primary molecular functions were activity of transmembrane receptor protein kinase, transmembrane receptor protein tyrosine kinase, and protein tyrosine kinase. KEGG analysis showed that the PI3K-Akt signaling pathway was closely related to the treatment of CHD with BSS by YXTMD. Molecular docking results showed that the core active components had a good binding activity with the core targets. The clinical trial results showed that YXTMD improved the BSS scores and decreased the serum levels of total cholesterol and low-density lipoprotein cholesterol. Moreover, the levels of PI3k and AKt mRNA were upregulated and the levels of GSK-3β mRNA were downregulated. YXTMD has multicomponent, multitarget, and multipathway effects in the treatment of CHD with BSS, and its mechanism of action may involve activation of the PI3K-AKt signaling pathway, downregulation of GSK-3β, and mediation of in vivo lipid metabolism-based metabolic processes. Hindawi 2022-09-30 /pmc/articles/PMC9546682/ /pubmed/36212940 http://dx.doi.org/10.1155/2022/4692217 Text en Copyright © 2022 Mengxue Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Mengxue
Liu, Jia
Zhang, Xiangzhuo
Zhang, Shumeng
Jiang, Yujie
Yu, Zixuan
Xie, Ting
Chen, Yuxia
Chen, Lingli
Li, Jie
Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking
title Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking
title_full Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking
title_fullStr Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking
title_full_unstemmed Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking
title_short Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking
title_sort mechanism of yangxin tongmai decoction in the treatment of coronary heart disease with blood stasis syndrome based on network pharmacology and molecular docking
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546682/
https://www.ncbi.nlm.nih.gov/pubmed/36212940
http://dx.doi.org/10.1155/2022/4692217
work_keys_str_mv AT zhangmengxue mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT liujia mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT zhangxiangzhuo mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT zhangshumeng mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT jiangyujie mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT yuzixuan mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT xieting mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT chenyuxia mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT chenlingli mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking
AT lijie mechanismofyangxintongmaidecoctioninthetreatmentofcoronaryheartdiseasewithbloodstasissyndromebasedonnetworkpharmacologyandmoleculardocking