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Phloretin ameliorates diabetic nephropathy by inhibiting nephrin and podocin reduction through a non-hypoglycemic effect.
Liu, Jia; Sun, Mingcheng; Xia, Yong; Cui, Xiaopei; Jiang, Jingjing.
Afiliación
  • Liu J; Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, PR China. jjj1601@126.com.
  • Sun M; Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, PR China. jjj1601@126.com.
  • Xia Y; Key Laboratory of Cardiovascular Proteomics of Shandong Province, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong, PR China.
  • Cui X; Key Laboratory of Cardiovascular Proteomics of Shandong Province, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong, PR China.
  • Jiang J; Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, PR China. jjj1601@126.com.
Food Funct ; 13(12): 6613-6622, 2022 Jun 20.
Article en En | MEDLINE | ID: mdl-35622066
Phloretin is a dihydrochalcone flavonoid from natural plants, which has protective activities against oxidative stress and inflammation. To date, its effect on diabetic nephropathy (DN) has not been investigated. In this study, we examined the potential role of phloretin in diabetes-induced renal damage and associated mechanisms in a type 2 diabetes mellitus (T2DM) model induced by streptozotocin (STZ) and high-fat diet (HFD) in Apolipoprotein E knockout (ApoE-/-) mice. We found that daily treatment with a low dose (20 mg kg-1) of phloretin, as a dietary supplement, significantly alleviated polyuria, proteinuria, and glomerular histopathological changes in the T2DM mice, indicating a protective effect of phloretin on diabetic renal dysfunction. In the phloretin-treated T2DM mice, major metabolic parameters, including blood glucose levels, were not altered significantly, suggesting that the observed beneficial effects of phloretin may be due to a mechanism independent of blood glucose control. Further experiments revealed that phloretin had a protective effect on glomerular podocytes as indicated by ameliorated glomerular basement membrane (GBM) thickening and podocyte foot process effacement. Moreover, phloretin treatment restored levels of nephrin and podocin, two podocyte slit diaphragm proteins that were decreased in T2DM mice. Our results indicate that low-dose phloretin treatment has a protective effect on podocytes in DN via a non-hypoglycemic mechanism in preserving nephrin and podocin expression levels. These data suggest that phloretin may be exploited as a novel therapeutic agent for DN.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 2 / Nefropatías Diabéticas / Podocitos Límite: Animals Idioma: En Revista: Food Funct Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 2 / Nefropatías Diabéticas / Podocitos Límite: Animals Idioma: En Revista: Food Funct Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido