The natural compound andrographolide inhibits human aortic valve interstitial cell calcification via the NF-kappa B/Akt/ERK pathway.
Aortic Valve
/ drug effects
Aortic Valve Stenosis
/ etiology
Biological Products
/ chemistry
Calcinosis
/ etiology
Cell Differentiation
/ drug effects
Computational Biology
/ methods
Disease Susceptibility
Diterpenes
/ chemistry
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Gene Expression Profiling
Humans
NF-kappa B
/ metabolism
Osteogenesis
/ drug effects
Proto-Oncogene Proteins c-akt
/ metabolism
RNA, Messenger
/ genetics
Signal Transduction
/ drug effects
Calcification
NF-κB
Natural product
Osteogenic differentiation
Valvular disease
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
06
12
2019
revised:
29
01
2020
accepted:
31
01
2020
pubmed:
18
2
2020
medline:
15
12
2020
entrez:
18
2
2020
Statut:
ppublish
Résumé
Calcific aortic valve disease (CAVD) is caused by valve interstitial cells (VICs) initiating the thickening and calcification of valve leaflets. The present study aimed to investigate whether andrographolide (AGP) could attenuate the calcification of human valve interstitial cells (hVICs). hVICs stimulated by osteoblastic medium (OM) were treated with or without AGP. RNA sequencing was utilized to investigate changes in gene expression. Cell growth and calcification of hVICs were assessed using a CCK8 assay and Alizarin Red S staining, respectively. The expression of the two calcification-related markers, RUNX2 and ALP, were quantified by qRT-PCR, Western blotting, and immunofluorescent staining. The results indicate that hVICs treated with OM plus AGP exhibited decreased Alizarin Red S staining compared with cells treated with OM only in addition to down-regulation of ALP and RUNX2. Mappings of differentially expressed genes (DEGs) in different groups using Venn diagrams during analysis of gene expression profiles, 653 common DEGs were identified that displayed different biological functions and signaling pathways after treatment with AGP. RELA, a core factor of the NF-κB pathway was inhibited by AGP in addition to phosphorylation of AKT and ERK1/2. Thus, AGP attenuated calcification of hVICs. These results demonstrate that AGP, a promising natural product, can attenuate the process of CAVD.
Identifiants
pubmed: 32066043
pii: S0753-3322(20)30176-1
doi: 10.1016/j.biopha.2020.109985
pii:
doi:
Substances chimiques
Biological Products
0
Diterpenes
0
NF-kappa B
0
RNA, Messenger
0
andrographolide
410105JHGR
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
109985Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest We declare that the authors have no conflict of interest.