Marein Ameliorates Myocardial Fibrosis by Inhibiting HIF-1α and TGF-ß1/Smad2/3 Signaling Pathway in Isoproterenol-stimulated Mice and TGF-ß1-stimulated Cardiac Fibroblasts.
Curr Pharm Des
; 30(1): 71-80, 2024.
Article
em En
| MEDLINE
| ID: mdl-38151839
ABSTRACT
BACKGROUND:
Myocardial fibrosis significantly contributes to the pathogenesis and progression of heart failure.OBJECTIVE:
We probe into the impact of marein, a key bioactive compound in functional food Coreopsis tinctoria, on isoproterenol-stimulated myocardial fibrotic mice and transforming growth factor ß1 (TGF-ß1)-stimulated cardiac fibroblasts (CFs).METHODS:
Isoproterenol was administered to the experimental mice via subcutaneous injection, and simultaneous administration of marein (25-100 mg/kg) was performed via oral gavage. CFs were stimulated with TGF- ß1 to trigger differentiation and collagen synthesis, followed by treatment with marein at concentrations of 5-20 µM.RESULTS:
Treatment with marein in mice and CFs resulted in a significant reduction in the protein expression levels of α-smooth muscle actin, collagen type I, and collagen type III. Additionally, marein treatment decreased the protein expression levels of TGF-ß1, hypoxia-inducible factor-1α (HIF-1α), p-Smad2/3, and Smad2/3. Notably, molecular docking analysis revealed that marein directly targets HIF-1α.CONCLUSION:
Marein might exert a protective function in isoproterenol-stimulated myocardial fibrotic mice and TGF-ß1-stimulated CFs, which might result from the reduction of TGF-ß1 induced HIF-1α expression, then inhibiting p-Smad2/3 and Smad2/3 expressions.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Chalconas
/
Fator de Crescimento Transformador beta1
/
Cardiomiopatias
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article