Abstract

The development of diabetes mellitus is related to oxidant stress induced by a high carbohydrate/high-fat diet (HFD). Quercetin, as a major bioactive component in Toona sinensis leaves (QTL), is a natural antioxidant. However, the exact mechanism by which QTL ameliorate diabetes mellitus is still unknown. In this study, we investigated the hypoglycemic effects and hepatocytes protection of QTL on HFD and alloxan induced diabetic mice. Intragastric administration of QTL significantly reduced body weight gain, serum glucose, insulin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase serum levels compared to those of diabetic mice. Furthermore, it significantly attenuated oxidative stress, as determined by lipid peroxidation, nitric oxide content, and inducible nitric oxide synthase activity and as a result attenuated liver injury. QTL also significantly suppressed the diabetes-induced activation of the p65/NF-κB and ERK1/2/MAPK pathways, as well as caspase-9 and caspase-3 levels in liver tissues of diabetic mice. Finally, micrograph analysis of liver samples showed decreased cellular organelle injury in hepatocytes of QTL treated mice. Taken together, QTL can be viewed as a promising dietary agent that can be used to reduce the risk of diabetes mellitus and its secondary complications by ameliorating oxidative stress in the liver.

Highlights

  • There is a global increase in the prevalence of diabetes mellitus (DM) which is predominantly related to changing lifestyle and the resulting surge in obesity

  • The liver dysfunction observed in type 1 and 2 diabetes is described as steatohepatitis, and many authors assign it to a wide group of liver pathologies called nonalcoholic fatty liver disease (NAFLD) [1,2,3]

  • high density lipoprotein cholesterol (HDL-C) levels were significantly (P < 0.01) lower in diabetic groups compared to those of the normal diet and normal diet supplemented with quercetin from T. sinensis leaves (QTL) groups

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Summary

Introduction

There is a global increase in the prevalence of diabetes mellitus (DM) which is predominantly related to changing lifestyle and the resulting surge in obesity. DM is a metabolic disease characterized by chronic hyperglycemia resulting from defects in insulin metabolism and impaired function of carbohydrate, lipid, and protein metabolism that leads to long-term complications. The liver dysfunction observed in type 1 and 2 diabetes is described as steatohepatitis, and many authors assign it to a wide group of liver pathologies called nonalcoholic fatty liver disease (NAFLD) [1,2,3]. Chronic oxidative stress mediated by glucolipotoxicity is involved in the onset and progression of diabetic liver dysfunction in both animal models and humans [4,5,6]. Regulating liver cell homeostasis and protecting the cells against oxidative surrounding are the most important, which calls for an effective antioxidant therapy as alternative in the management of NAFLD [7,8,9,10]

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