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Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy

OBJECTIVE: Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biolo...

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Autores principales: Jiang, Shisheng, Huang, Chaoming, Wang, Shulin, Huang, Biyun, Wu, Dan, Zheng, Guodong, Cai, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906983/
https://www.ncbi.nlm.nih.gov/pubmed/35281609
http://dx.doi.org/10.1155/2022/4293265
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author Jiang, Shisheng
Huang, Chaoming
Wang, Shulin
Huang, Biyun
Wu, Dan
Zheng, Guodong
Cai, Yi
author_facet Jiang, Shisheng
Huang, Chaoming
Wang, Shulin
Huang, Biyun
Wu, Dan
Zheng, Guodong
Cai, Yi
author_sort Jiang, Shisheng
collection PubMed
description OBJECTIVE: Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy. RESULTS: We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1. CONCLUSION: CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.
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spelling pubmed-89069832022-03-10 Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy Jiang, Shisheng Huang, Chaoming Wang, Shulin Huang, Biyun Wu, Dan Zheng, Guodong Cai, Yi Biomed Res Int Research Article OBJECTIVE: Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy. RESULTS: We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1. CONCLUSION: CRP could inhibit myocardial hypertrophy through multitarget and multiapproach. Hindawi 2022-03-02 /pmc/articles/PMC8906983/ /pubmed/35281609 http://dx.doi.org/10.1155/2022/4293265 Text en Copyright © 2022 Shisheng Jiang 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
Jiang, Shisheng
Huang, Chaoming
Wang, Shulin
Huang, Biyun
Wu, Dan
Zheng, Guodong
Cai, Yi
Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy
title Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy
title_full Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy
title_fullStr Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy
title_full_unstemmed Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy
title_short Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy
title_sort network pharmacology-based strategy for predicting therapy targets of citri reticulatae pericarpium on myocardial hypertrophy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906983/
https://www.ncbi.nlm.nih.gov/pubmed/35281609
http://dx.doi.org/10.1155/2022/4293265
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