Studies On Hypoglycemic Effects And The Mechanism Of Polysaccharides From Radix Codonopsis

Diabetes Mellitus have become the third serious disease that threaten seriously mankind health behind heaert-cerebrovascular and cancer. Diabetes Mellitus involved an inability to regulate plasma glucose within the normal rang. It is characterized by an insulin deficiency, leading to hyperglycemia, glycosuria, and polyuria.There are two forms of diabetes: insulin-dependent diabetes mellitus(IDDM, typeⅠ), whose pancreaticβ-cell are destroyed by an autoimmune reaction, leading to a complete lack of insulin, and insulin is the only effective agent to treat IDDM; and non-insulin-dependent diabetes mellitus(NIDDM, typeⅡ), which is caused by multi-factors including pancreaticβ-cell defect, tissue sensitivity reduction, and insulin resistance. Though we can select different kinds of drugs to treat diabetes mellitus, oral hypoglycemic drugs have many adverse reaction and toxic effects. The adverse reaction and Smoggy caused by vein injection insulin for a long time make us to find a better drug in Chinese traditional medicine. Thus it is becoming a focus in medical research to original hypoglycemic agent in Chinese traditional medicine.According to the recent study about hypoglycemic effect of the plant polysaccharides and its mechanisms, it indicates that the hypoglycemic effect of the plant polysaccharides is due to several mechanisms, including the plant polysaccharides can promote the effect of hypoglycemic hormone, adjust the content of hepatic glycogen, preserve islet cells, promote the utilization of the blood glucose by the periphery tissue and organs, meanwhile, depress the effect of hypoglycemia hormone, regulate the activity of glycometabolic enzyme.Polysaccharides from Radix Codonopsis are extracted from Codonopsipilosula(Franch.)Nannf which belongs to Campanulanceae,including monosaccharide and its derivant. Polysaccharides from Radix Codonopsis has many pharmacological effects in regulating immune function,hematopoietic function, and radical free scavenging and so on. Now, there is no research on Polysaccharides from Radix Codonopsis's effect on Diabetes Mellitus, we studied the hypoglycemic effects and the mechanism of Polysaccharides from Radix Codonopsis.Methods: Fasting blood glucose(FBG) was observed in both normal mice and diabetic model mice that induced by Epinephrine(sc, 0.25 mg/kg)to evaluate the hypoglycemic effects of Polysaccharides from Radix Codonopsis (ig, 300,200,100 mg/kg), and liver glycogen was also measured to observed the influence of Polysaccharides from Radix Codonopsis on glucose metabolism. In the further, fasting blood glucose, liver glycogen were determined to evaluate the hypoglycemic effects of Polysaccharides from Radix Codonopsis on diabetic model mice that induced by alloxan (ip, 200 mg/kg), the level of insulin were measured the activity of super oxide dismutase(SOD) and the content of malondialdehyde(MDA), the level of total cholesterol(TC), triglyceride(TG) in serum were also measured. In addition, the variety of blood glucose after ip alanine(2g/kg) was measured to determine the effect of Polysaccharides from Radix Codonopsis on gluconeogenesis in normal mice. At last, the variety of blood glucose after ip insulin was determined to measure the influence of Polysaccharides from Radix Codonopsis on insulin sensitivity in insulin resistance model mice induce by hydrocortisone sodium succinate (HCSS)(sc, 70 mg/kg).Results:1. Polysaccharides from Radix Codonopsis(ig, 300,200,100mg/kg)had not significantly influenced the fasting blood glucose of normal mice (P >0.05).2. In diabetic mice induced by Epinephrine, FBG increased significantly in model group from 30min to 90min, liver glycogen decreased in 90min. Compared to the model control group. Polysaccharides from Radix Codonopsis showed obvious effects on inhabiting the raise of blood glucose and increasing the reduction of liver glycogen 90min (P <0.05 or P <0.01).We had a conclusion that Polysaccharides from Radix Codonopsis possessed an hypoglycemic effect on above experimental hyperglycemia models.3. In diabetic mice induced by alloxan, FBG increased significantly in model group. Compared to the model control group,3.1 Polysaccharides from Radix Codonopsis decreased the FBG and significantly enhanced the liver glycogen (P <0.05 or P <0.01); we can presume that Polysaccharides from Radix Codonopsis can decrease blood glucose by promoting the regulation of blood glucose by body self.3.2 Polysaccharides from Radix Codonopsis effectively increased the insulin in serum, and improved the insulin sensitivity (P <0.05 or P <0.01). The absolute or relative deficiency of insulin secretion is the pathologic foundation of Diabetes Mellitus. The result suggests that Polysaccharides from Radix Codonopsis could improve the secretion of insulin.3.3 Polysaccharides from Radix Codonopsis effectively enhanced the activity of SOD, reduced the MDA content in serum (P <0.05 or P <0.01). From the result, we can conclude that Polysaccharides from Radix Codonopsis can improve the ability of eliminating free radical, which was a good preventing the incidence of Diabetes Mellitus.3.4 Polysaccharides from Radix Codonopsis significantly reduced the TC, TG content in serum (P <0.05 or P <0.01). The results suggested that Polysaccharides from Radix Codonopsis could improve the disorder of the serum lipid metabolism。4. Compared to the model control group with a rate of 37.3%, Polysaccharides from Radix Codonopsis possessed good inhibiting on in normal mice with the rates were 21.7%,23.4%,25.1% respectively (P <0.05 or P <0.01). The result demonstrated that gluconeogensis could be inhibited by Polysaccharides from Radix Codonopsis.5. In insulin resistance model mice induce by sc HCSS,FBG almost unchanged in 0min. Compared to normal group, Polysaccharides from Radix Codonopsis significantly decreased the FBG in 30 min (P <0.05 or P <0.01) and return in 120min. It indicated that Polysaccharides from Radix Codonopsis improved the insulin resistance.In conclusion, Polysaccharides from Radix Codonopsis possess a significant hypoglycemic effect in experimental diabetic mice; be able to regulate the glucose metabolism by promoting the synthesis of glycogen and inhibiting gluconeogensisi in diabetic mice; enhance the secretion of insulin, improve the insulin resistance; promote the ability of eliminating free radical, inhibit the lipid peroxidation; also can regulate the disorder of the serum lipid metabolism.