Hypoglycemic Effect Of Ganoderma Lucidum Polysaccharides And Its Possible Mechanism

Along with rapid economic development, diabetes prevalence has increased dramatically. Hyperglycaemia is an important risk factor of cardiovascular disease, later is a leading cause of death. Ganoderma lucidum polysaccharides (Gl-PS), as one of the most important bioactivities chemical in Ganoderma lucidum, a kind of Chinese Traditional Medicine, have been demonstrated that have lowering-glucose property. However, the mechanism of hypoglycemic effect of Gl-PS on streptozotocin (STZ)-induced diabetes rats haven't reported yet. The aim of the present study was to investigate 1) the effect of Gl-PS on STZ-induced diabetes rats; 2) the mechanism of hypoglycemic effect of Gl-PS.Crude Gl-PS were prepared from Ganoerma lucidum fruiting body by hot-water extraction. Gl-PS was purified by micro filtration methods. We have analyzed the primary characteristics of Gl-PS (purchased from company). The results showed that the Gl-PS was a homogeneous polysaccharide with an average molecular weight of 8849Da. The amino acid and protein analysis indicated that Gl-PS was considered as protein-bound polysaccharides. The monosaccharide composition of Gl-PS was glucose:galactose:arabinose:mannose=22.4:1.9:1.0:2.1. In addition, the Infrared Spectrum analysis showed the existence ofβ-configuration of the sugar units in Gl-PS. The DPPH study showed that Gl-PS exhibited a 5% ability of radical-scavenging activity when compared with vitamin C. Moreover, Gl-PS had an antioxidant action in scavenging superoxide anion radical, hydroxide radical and reducing power in vitro.In order to investigate the mechanisms of hypoglycemic effect of Gl-PS, we have conducted an animal study. Forty of fifty male SD rats (weighing 250±30 g) were induced by a single injection with 65 mg/kg STZ. The successful model of type 1 diabetes rats were confirmed by plasma glucose estimation in addition to polyuria and other diabetic features. The rats having a fasting plasma glucose level of above 250 mg/dL (13.9 mmol/L) were considered as diabetic rats. The diabetic rats were divided into Gl-PS (200 mg/kg Gl-PS), metformin (100 mg/kg metformin) and diabetic (n=10 per group) three groups. The rest healthy rats (n=10) were considered as control group.After 8 weeks, the plasma concentrations of fasting blood glucose, triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), nitric oxide (NO), blood urea nitrogen (BUN) and creatinine (Cr) in M group and G group were significantly lower than D group, while HDL-C were significantly higher than D group (P<0.05). In addition, the urine glucose and urine protein reduction were also observed. The histopathological observations showed that Gl-PS or metformin could ameliorate the pathological changes in pancreas and kidney. The levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in pancreas and kidney tissue were significantly increased in G and M groups when compared with D group (P<0.05). And, the mRNA expression of bcl-2 and PDX-1 were significantly increased in G and M groups when compared with D group, while bax, iNOS and casp-3 were significantly decreased.In summary, our results suggested that Gl-PS with a molecular weight be of 8849Da could significant decrease fasting plasma blood glucose. And these beneficial effects might owe to its antioxidant activities and ability of scavenging surplus NO production caused by STZ thereby inhibiting apoptosis of pancreasβ-cells. In addition, Gl-PS could protect pancreatic tissues via up-regulating PDX-1 and bcl-2 mRNA expression and down-regulating the bax and casp-3 expression thereby inhibitingβ-cells apoptosis and promotingβ-cells regeneration. Moreover, we found that Gl-PS could ameliorate the early symptom of diabetic nephropathy.