Diacerein alleviates Ang II-induced cardiac inflammation and remodeling by inhibiting the MAPKs/c-Myc pathway.
Phytomedicine
; 106: 154387, 2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-36027716
ABSTRACT
BACKGROUND:
Heart failure is a common event in the course of hypertension. Recent studies have highlighted the key role of the non-hemodynamic activity of angiotensin II (Ang II) in hypertension-related cardiac inflammation and remodeling. A naturally occurring compound, diacerein, exhibits anti-inflammatory activities in various systems. HYPOTHESIS/PURPOSE:
In this study, we have examined the potential effects of diacerein on Ang II-induced heart failure.METHODS:
C57BL/6 mice were administered Ang II by micro-osmotic pump infusion for 4 weeks to develop hypertensive heart failure. Mice were treated with diacerein by gavage for final 2 weeks. RNA-sequencing analysis was performed to explore the potential mechanism of diacerein.RESULTS:
We found that diacerein could inhibit inflammation, myocardial fibrosis, and hypertrophy to prevent heart dysfunction, without the alteration of blood pressure. To explore the potential mechanism of diacerein, RNA-sequencing analysis was performed, indicating that MAPKs/c-Myc pathway is involved in that cardioprotective effects of Diacerein. We further confirmed that diacerein inhibits Ang II-activated MAPKs/c-Myc pathway to reduce inflammatory response in mouse hearts and cultured cardiomyocytes. Deficiency of MAPKs or c-Myc in cardiomyocytes abolished the anti-inflammatory effects of diacerein.CONCLUSION:
Our results indicate that diacerein protects hearts in Ang II-induced mice through inhibiting MAPKs/c-Myc-mediated inflammatory responses, rendering diacerein a potential therapeutic candidate agent for hypertensive heart failure.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Cardíaca
/
Hipertensão
/
Cardiomiopatias
Limite:
Animals
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2022
Tipo de documento:
Article