Asiatic acid protects against pressure overload-induced heart failure in mice by inhibiting mitochondria-dependent apoptosis.
Free Radic Biol Med
; 208: 545-554, 2023 11 01.
Article
en En
| MEDLINE
| ID: mdl-37717794
BACKGROUND: Mitochondrial dysfunction and subsequent cardiomyocyte apoptosis significantly contribute to pressure overload-induced heart failure (HF). A highly oxidative environment leads to mitochondrial damage, further exacerbating this condition. Asiatic acid (AA), a proven antioxidant and anti-hypertrophic agent, might provide a solution, but its role and mechanisms in chronic pressure overload-induced HF remain largely unexplored. METHODS: We induced pressure overload in mice using transverse aortic constriction (TAC) and treated them with AA (100 mg/kg/day) or vehicle daily by oral gavage for 8 weeks. The effects of AA on mitochondrial dysfunction, oxidative stress-associated signaling pathways, and overall survival were evaluated. Additionally, an in vitro model using hydrogen peroxide-exposed neonatal rat cardiomyocytes was established to further investigate the role of AA in oxidative stress-induced mitochondrial apoptosis. RESULTS: AA treatment significantly improved survival and alleviated cardiac dysfunction in TAC-induced HF mice. It preserved mitochondrial structure, reduced the LVW/BW ratio by 20.24%, mitigated TAC-induced mitochondrial-dependent apoptosis by significantly lowering the Bax/Bcl-2 ratio and cleaved caspase-9/3 levels, and attenuated oxidative stress. AA treatment protected cardiomyocytes from hydrogen peroxide-induced apoptosis, with concurrent modulation of mitochondrial-dependent apoptosis pathway-related proteins and the JNK pathway. CONCLUSIONS: Our findings suggest that AA effectively combats chronic TAC-induced and hydrogen peroxide-induced cardiomyocyte apoptosis through a mitochondria-dependent mechanism. AA reduces cellular levels of oxidative stress and inhibits the activation of the JNK pathway, highlighting its potential therapeutic value in the treatment of HF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Insuficiencia Cardíaca
/
Peróxido de Hidrógeno
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2023
Tipo del documento:
Article
Pais de publicación:
Estados Unidos