Research Article: Antidiabetic activities of polysaccharides separated from Inonotus obliquus via the modulation of oxidative stress in mice with streptozotocin-induced diabetes

Date Published: June 29, 2017

Publisher: Public Library of Science

Author(s): Juan Wang, Wenji Hu, Lanzhou Li, Xinping Huang, Yange Liu, Di Wang, Lirong Teng, M. Faadiel Essop.


This study evaluated the effects of Inonotus obliquus polysaccharides (IOs) on diabetes and other underlying mechanisms related to inflammatory factors and oxidative stress in a mouse model of streptozotocin (STZ)-induced diabetes. Four weeks administration of metformin (120 mg/kg) and IO1-4 (50%-80% alcohol precipitation), or IO5 (total 80% alcohol precipitation) at doses of 50 mg/kg reverses the abnormal changes of bodyweights and fasting blood glucose levels of diabetic mice. IOs significantly increased the insulin and pyruvate kinase levels in serum, and improved the synthesis of glycogen, especially for IO5. IOs restored the disturbed serum levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde. The down-regulation of interleukin-2 receptor, matrix metalloproteinase-9, and the enhancement of interleukin-2 in serum of diabetic mice were significantly attenuated by IOs. Histologic and morphology examinations showed that IOs repaired the damage on kidney tissues, inhibited inflammatory infiltrate and extracellular matrix deposit injuries in diabetic mice. Compared with untreated diabetic mice, IOs decreased the expression of phosphor-NF-κB in the kidneys. These results show that IOs treatment attenuated diabetic and renal injure in STZ-induced diabetic mice, possibly through the modulation of oxidative stress and inflammatory factors. These results provide valuable evidences to support the use of I. obliquus as a hypoglycemic functional food and/or medicine.

Partial Text

Diabetes mellitus is a serious metabolic disease that results from an absolute or relative lack of insulin and chronic hyperglycemia [1]. It includes a group of autoimmune, hormonal, heterogeneous, and metabolic disorders and is usually accompanied by obesity (hyperphagia), a high blood glucose level, selective loss of pancreatic islet β-cell mass, and microvascular complications [2]. Type 1 and type 2 diabetes are both characterized by chronic hyperglycemia, which contributes to various diabetic complications such as nephropathy, retinopathy, neuropathy, and cardiomyopathy [3]. Among these complications, diabetic nephropathy is considered to be a major cause of end-stage renal disease, which is responsible for overall morbidity and mortality in patients with kidney diseases [4]. Oxidative stress is a condition of imbalance caused by the excess formation of free radicals and decreased activity of antioxidant defense systems. Under diabetic conditions, the chronic presence of high glucose levels enhances the production of reactive oxygen species (ROS) from protein glycation and glucose autoxidation [5]. These irreversible oxidative modifications modulate redox-sensitive signaling pathways and lead to altered inflammation, endothelial dysfunction, impaired secretion of insulin, and impaired use of glucose in the peripheral tissues [6]. Many plant extracts are known to restore these parameters in streptozotocin (STZ)-induced diabetes rats, and have been found to delay diabetic complications as a result of their antioxidant potential [7]. However, currently available drugs for diabetes mellitus show many limitations, such as adverse effects, limited efficacy, and high rates of secondary failure [2]. Therefore, there is a strong incentive to develop new hypoglycemic agents, and the search for appropriate hypoglycemic agents has recently focused on natural products [8].

STZ-induced diabetes is characterized by pancreatic β-cell damage and insufficient insulin synthesis [29], which are all related to oxyradicals. In this study, sharply reduced bodyweights and increased fasting blood glucose levels were observed in mice with STZ-induced diabetes, and both were significantly reversed by administration of IOs. We were encouraged to find that IOs enhanced the serum levels of insulin, indicating their amelioration of the metabolic disturbance of glucose enzymes in diabetic mice. Different from other agents for diabetes treatment, IOs contains multiple polysaccharides which will show “systemically targets” to eliminate the symptoms of diabetes in a much natural way including anti-oxidation.




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