Nimbolide protects against diabetic cardiomyopathy by regulating endoplasmic reticulum stress and mitochondrial function via the Akt/mTOR pathway.
Tissue Cell
; 90: 102478, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-39053131
ABSTRACT
Nimbolide has been demonstrated to possess protective properties against gestational diabetes mellitus and diabetic retinopathy. However, the role and molecular mechanism of nimbolide in diabetic cardiomyopathy (DCM) remain unknown. Diabetes was induced in rats via a single injection of streptozotocin (STZ) and then the diabetic rats were administered nimbolide (5â¯mg/kg and 20â¯mg/kg) or dimethyl sulfoxide daily for 12 weeks. H9c2 cardiomyocytes were exposed to high glucose (25â¯mM glucose) to mimic DCM in vitro. The protective effects of nimbolide against DCM were evaluated in vivo and in vitro. The potential molecular mechanism of nimbolide in DCM was further explored. We found that nimbolide dose-dependently decreased blood glucose and improved body weight of diabetic rats. Additionally, nimbolide dose-dependently improved cardiac function, alleviated myocardial injury/fibrosis, and inhibited endoplasmic reticulum (ER) stress and apoptosis in diabetic rats. Moreover, nimbolide dose-dependently improved mitochondrial function and activated the Akt/mTOR signaling. We consistently demonstrated the cardioprotective effects of nimbolide in an in vitro model of DCM. The involvement of ER stress and mitochondrial pathways were further confirmed by using inhibitors of ER stress and mitochondrial division. By applying a specific Akt inhibitor SC66, the cardioprotective effects of nimbolide were partially blocked. Our study indicated that nimbolide alleviated DCM by activating Akt/mTOR pathway. Nimbolide may be a novel therapeutic agent for DCM treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Limoninas
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Diabetes Mellitus Experimental
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Proteínas Proto-Oncogénicas c-akt
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Cardiomiopatías Diabéticas
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Serina-Treonina Quinasas TOR
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Estrés del Retículo Endoplásmico
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Mitocondrias
Límite:
Animals
Idioma:
En
Revista:
Tissue Cell
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido