Study On The Hypoglycemic Efficacy And Mechanism Of Cyclocarya Paliurus And Its Compound Compatibility On Hyperglycemic Rat

The incidence of diabetes has increased year by year,which has become the fourth major disease threatening human health.Diabetes complications are numerous,seriously endangering people’s lives.To find safe and effective prevention and treatment for them has always been a hot research in medicine.Cyclocarya paliurus,a rare species in China,which has been the tea folk cure for diabetes for a long time and its hypoglycemic effect is widely confirmed by scientists.In the early stage,the research group has studied the hypoglycemic effect of the Cyclocarya paliurus and its compound on type 1 diabetic mice induced by alloxan,and the effect is obvious.In order to further explore the mechanism of hypoglycemic action of Cyclocarya paliurus.On the basis of previous studies,the research group started from the perspective of diabetes leading by oxidative stress and explored the mechanism of Cyclocarya paliurus by relieving oxidative stress to reduce blood glucose.1 literature research1.1 Analysis of the hypoglycemic effect and development prospect of Cyclocarya paliurus Conduct a comprehensive review of the relevant literature on the medicinal value of the Cyclocarya paliurus.To clarify the pharmacological effects of lowering blood glucose,reducing blood lipid,antioxidation and improving immunity.As a traditional Chinese medicine,it is necessary to further study its flavor,tropism,compatibility to provide the basis for the wider clinical use.1.2 Preparation of diabetic rat model Review the current literature on all models of diabetes.Summary the influencing factors of diabetic rat model.Combing with various factors,choose the most suitable model for diabetic disease.1.3 The mechanism of oxidative stress leading to the onset of diabetes Review the literature on the pathogenesis of diabetes;summary the pathways by which oxidative stress leading to diabetes.2 Experimental study2.1 Cyclocarya paliurus on diabetic rats The diabetic rat model was successfully established,and observed the effects of Cyclocarya paliurus on glucose metabolism,lipid metabolism,liver pathological morphology and its medicinal qualities.2.1.1 Cyclocarya paliurus on OTCC The results showed that after 4 weeks,Cyclocarya paliurus can significantly reduce the area under the curve of blood glucose(P<0.05).2.1.2 Cyclocarya paliurus on liver lipid Frozen oil red O staining showed that:Cyclocarya paliurus can significantly improve fatty liver changes,reducing the ballooning degeneration of liver cells;serum biochemical results showed that Cyclocarya paliurus reduce serum PPAR levels,but with no statistical difference.2.1.3 Cyclocarya paliurus on medicinal properties Serum biochemical results showed that there was a trend of decreasing serum cAMP and cGMP level,but there was no statistical difference.The above results showed that the effect of single herb medicine on reducing the blood glucose level of rats could effectively improve the level of glucose tolerance in diabetic rats.Reduce the hepatic steatosis.The effect of FBG and lipid metabolism is not obvious.The medicine has the trend of cold medicine trend,so it is necessary to further study the compatibility of drugs in order to explore the hypoglycemic effect and mechanism.2.2 The effect of compound prescription of Cyclocarya paliurus on diabetic rats Observe the effect of Cyclocarya paliurus compound on sugar metabolism,pancreatic pathology,insulin content and oxidative stress index in diabetes model rats.Observe the effect of oxidative stress on two pathway components related to diabetes.2.2.1 The effect of Cyclocarya paliurus compound on blood glucose The serum biochemical indexes,the results showed that Cyclocarya paliurus compound FBG was significantly decreased(P<0.05 P<0.01),starting from the first week,showing hypoglycemic effect is obvious,and the hypoglycemic effect is sustained and stable,especially in low dose group.Improving the glucose tolerance in diabetic rats,the area of Cyclocarya paliurus compound low dose group under the curve of blood glucose decreased significantly(P<0.01);Reduce insulin resistance.The serum IR level in Cyclocarya paliurus compound low dose group was significantly decreased(P<0.05).2.2.2 The effect on islet cell morphology and insulin content Pancreatic pathological HE staining showed that the Cyclocarya paliurus compound can significantly improve pancreatic tissue morphological changes,the protection of pancreatic islet cell;Immune tissue slice staining showed that Cyclocarya paliurus compound low dose group promote the secretion of insulin(P<0.05).2.2.3 The effect on oxidative stress index Liver antioxidant enzyme levels showed that Cyclocarya paliurus compound in high dose group increase the content of liver SOD and CAT(P<0.01),Cyclocarya paliurus in high dose group increase the level of liver GSH-px(P<0.05),the MDA change was not statistically difference.The results showed that the high dose group reduce the level of 8-OHDG in kidney(P<0.01).2.2.4 The effect on pathway components of oxidative stress in diabetes2.2.4.1 Pathway elements related to the insulin secretion The expression of P-JNK,JNK,PDX-1 protein level in pancreatic tissue were detected by Western-blot.Cyclocarya paliurus compound in low,middle and high dose could significantly reduce the expression level of PJNK protein in pancreatic tissue(P<0.01 P<0.05);Cyclocarya paliurus low,medium and high dose group reduce the expression level of JNK protein in pancreatic tissue(P<0.01);Cyclocarya paliurus compound had no significant effect on the expression level of PDX-1 protein in pancreatic tissue.2.2.4.2 Pathway elements related to the insulin resistance The expression levels of InsR,IRS,PI3K,GLUT4 protein were detected by Western-blot in skeletal muscle tissue.Cyclocarya paliurus compound in high dose group increase the expression level of InsR protein(P<0.05);increased the expression level of IRS1 protein(P<0.01);increased the expression level of PI3K protein(P<0.05);Cyclocarya paliurus low and high dose group increased the expression level of GLUT4 protein in skeletal muscle(P<0.05).The results showed that the compound could significantly improve the level of FBG and improve the level of antioxidant enzymes in rats.It has a positive effect on insulin secretion related components;protect islet cells;increase insulin secretion;promote insulin signal transduction and reduce insulin resistance.The innovation of this subject1 Study the properties of Chinese herbal medicine.2 Study the effect of compound prescription on oxidative stress.3 Study Cyclocarya paliurus compound’s effect on the pathway components of oxidative stress in diabetes,JNK-PDX-1 pathway increased by adjusting the muscle insulin;enhancement mechanism of islet signaling by regulating InsR-IRS-PI3K-GLUT4 pathway.