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Ginsenoside Rb1 ameliorates lipotoxicity-induced myocardial injury in diabetes mellitus by regulating Mfn2.
Ji, Louyin; Han, Hui; Shan, Xiaoli; Zhao, Pei; Chen, Huihua; Zhang, Chen; Xu, Ming; Lu, Rong; Guo, Wei.
Afiliación
  • Ji L; School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: 495627729@qq.com.
  • Han H; School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: hanhui09292023@163.com.
  • Shan X; School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: shanxiaoli78@163.com.
  • Zhao P; School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: zp1737@sina.com.
  • Chen H; School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: chenhuihua@shutcm.edu.cn.
  • Zhang C; Department of Pathology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: zhangchen@shutcm.edu.cn.
  • Xu M; Department of Physiology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: mingxu@shutcm.edu.cn.
  • Lu R; School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: lurong@shutcm.edu.cn.
  • Guo W; Department of Pathology, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: weiguo@shutcm.edu.cn.
Eur J Pharmacol ; 974: 176609, 2024 Jul 05.
Article en En | MEDLINE | ID: mdl-38677536
ABSTRACT

PURPOSE:

Diabetic cardiomyopathy is a prevalent cardiovascular complication of diabetes mellitus. This study aimed to investigate the effects of ginsenoside Rb1 (GRb1) on the diabetic myocardium.

METHODS:

Leptin receptor-deficient db/db mice and palmitic acid (PA)-treated cardiomyocyte models were utilized. Cardiac systolic and diastolic function, mitochondrial morphology, and respiratory chain function were determined. The expression of mitochondrial dynamics proteins was measured. Mitofusin 2 (Mfn2) overexpression and inhibition were achieved by lentiviral infection and small interfering RNA (siRNA) transfection.

RESULTS:

In comparison to non-diabetic mice, db/db mice exhibited significant increases in body weight, blood glucose, blood lipids, and cardiac free fatty acid levels. This was accompanied by myocardial hypertrophy and left ventricular diastolic dysfunction, which were significantly ameliorated by GRb1 intervention. Stimulation with PA increased oxidative stress and apoptosis, and decreased viability in H9c2 cardiomyocytes. PA also reduced sarcomere contractility and relaxation in adult mice ventricular myocytes. PA-induced cellular and mitochondrial damage were reversed with GRb1 treatment. The cardiac tissue of db/db mice and PA-treated cardiomyocytes exhibited a decrease in Mfn2 expression, which was markedly improved by GRb1. Mfn2 overexpression reversed PA-induced mitochondrial fragmentation and functional damage in cardiomyocytes, while inhibition of Mfn2 expression by siRNA transfection blocked the protective effects of GRb1.

CONCLUSION:

GRb1 alleviated myocardial lipid accumulation and mitochondrial injury, and attenuated ventricular diastolic dysfunction in diabetic mice. The regulation of Mfn2 was involved in the protective effects of GRb1 against lipotoxic myocardial injury.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Miocitos Cardíacos / Ginsenósidos / Cardiomiopatías Diabéticas / GTP Fosfohidrolasas Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Miocitos Cardíacos / Ginsenósidos / Cardiomiopatías Diabéticas / GTP Fosfohidrolasas Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos