Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy.
Journal
BioMed research international
ISSN: 2314-6141
Titre abrégé: Biomed Res Int
Pays: United States
ID NLM: 101600173
Informations de publication
Date de publication:
2022
2022
Historique:
received:
22
01
2022
accepted:
12
02
2022
entrez:
14
3
2022
pubmed:
15
3
2022
medline:
9
4
2022
Statut:
epublish
Résumé
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. 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. 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. CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.
Identifiants
pubmed: 35281609
doi: 10.1155/2022/4293265
pmc: PMC8906983
doi:
Substances chimiques
Drugs, Chinese Herbal
0
PPAR gamma
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4293265Informations de copyright
Copyright © 2022 Shisheng Jiang et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest.
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