Cargando…

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

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 a...

Descripción completa

Detalles Bibliográficos
Autores principales: Jia, Li-ying, Cao, Gui-yun, Li, Jia, Gan, Lu, Li, Jin-xin, Lan, Xin-yi, Meng, Zhao-qing, He, Xin, Zhang, Chun-feng, Wang, Chong-Zhi, Yuan, Chun-Su
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316858/
https://www.ncbi.nlm.nih.gov/pubmed/34335263
http://dx.doi.org/10.3389/fphar.2021.698981
_version_ 1783729951708545024
author Jia, Li-ying
Cao, Gui-yun
Li, Jia
Gan, Lu
Li, Jin-xin
Lan, Xin-yi
Meng, Zhao-qing
He, Xin
Zhang, Chun-feng
Wang, Chong-Zhi
Yuan, Chun-Su
author_facet Jia, Li-ying
Cao, Gui-yun
Li, Jia
Gan, Lu
Li, Jin-xin
Lan, Xin-yi
Meng, Zhao-qing
He, Xin
Zhang, Chun-feng
Wang, Chong-Zhi
Yuan, Chun-Su
author_sort Jia, Li-ying
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8316858
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-83168582021-07-29 Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation Jia, Li-ying Cao, Gui-yun Li, Jia Gan, Lu Li, Jin-xin Lan, Xin-yi Meng, Zhao-qing He, Xin Zhang, Chun-feng Wang, Chong-Zhi Yuan, Chun-Su Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-07-14 /pmc/articles/PMC8316858/ /pubmed/34335263 http://dx.doi.org/10.3389/fphar.2021.698981 Text en Copyright © 2021 Jia, Cao, Li, Gan, Li, Lan, Meng, He, Zhang, Wang and Yuan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Jia, Li-ying
Cao, Gui-yun
Li, Jia
Gan, Lu
Li, Jin-xin
Lan, Xin-yi
Meng, Zhao-qing
He, Xin
Zhang, Chun-feng
Wang, Chong-Zhi
Yuan, Chun-Su
Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation
title Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation
title_full Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation
title_fullStr Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation
title_full_unstemmed Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation
title_short Investigating the Pharmacological Mechanisms of SheXiang XinTongNing Against Coronary Heart Disease Based on Network Pharmacology and Experimental Evaluation
title_sort investigating the pharmacological mechanisms of shexiang xintongning against coronary heart disease based on network pharmacology and experimental evaluation
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316858/
https://www.ncbi.nlm.nih.gov/pubmed/34335263
http://dx.doi.org/10.3389/fphar.2021.698981
work_keys_str_mv AT jialiying investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT caoguiyun investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT lijia investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT ganlu investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT lijinxin investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT lanxinyi investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT mengzhaoqing investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT hexin investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT zhangchunfeng investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT wangchongzhi investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation
AT yuanchunsu investigatingthepharmacologicalmechanismsofshexiangxintongningagainstcoronaryheartdiseasebasedonnetworkpharmacologyandexperimentalevaluation