Study Of The Blended Tea On Improving T2DM In Mice Based On Balanced Glycolipid Metabolism

There is increasing evidence that liver protective drugs for Type 2 diabetes mellitus（T2DM）are the preferred treatment option for T2DM with liver disease.Blended tea extracts contain a variety of plant components that may have better medicinal quality and/or lower hepatotoxicity than the plant components alone.The hypoglycemic potential of Cyclocarya paliurus（Batal.）Iljinsk.,Fu brick tea,vine tea and Lithocarpus litseifolius（Hance）Chun has attracted people’s attention.In this study,Cyclocarya paliurus（Batal.）Iljinskaja,Fu brick tea,vine tea and Lithocarpus litseifolius（Hance）Chun were mixed in a proportion.A mouse model of T2DM was established by combining high-fat and high-sugar diet with streptozotocin(120 mg.kg^-1)to explore the efficacy and mechanism of different doses of blended tea in T2DM intervention.The preli minary study on its hypoglycemic mechanism mainly involves liver protection and regulation of intestinal flora.It provides effective theoretical support and scientific basis for the development of blended tea with precise balance of glycolipid metabolism to improve T2DM.The main results are as follows:（1）According to the results of sensory evaluation and physico-chemical composition,it is determined that the mixing ratio of Cyclocarya paliurus（Batal.）Iljinsk.,Fu brick tea,vine tea and Lithocarpus litseifolius（Hance）Chun is 35.71:35.71:19.05.9.53.The water extract of blended tea contained 5.90±0.24%soluble sugars,3.37±0.24%polyphenols,and5.43±0.36%flavonoids.（2）The results showed that compared with control group,T2DM mice induced by high-fat and high-sugar diet combined with streptozotocin showed obvious symptoms,such as polydipsia,weight loss and fasting blood glucose increase（FBG）,in addition to significantly impaired glucose tolerance,insulin resistance,hyperlipidemia and islet atrophy（P<0.05）.These results indicated that high-fat and high-sugar diets combined with streptozotocin induced T2DM mouse model was successfully established.（3）Low-dose blended tea can significantly improve glucose and lipid metabolism disorder in T2DM mice.Compared with T2DM model group,low-dose blended tea could improve"three more and one less"symptoms caused by T2DM;The area under the glucose curve（AUC）and insulin resistance index in low-dose blended tea group decreased by41.54%and 48.40%,respectively,and significantly improved impaired glucose tolerance and insulin resistance;Low-dose blended tea reduced pancreatic damage;Serum TC,TG and LDL-C contents in low-dose blended tea group decreased by 34.07%,30.64%and38.50%,respectively,and HDL-C content increased by 23.81%,improved the blood lipid disorders caused by T2DM;The levels of IL-1βand TNF-αin low-dose tea group decreased by 35.09%and 48.66%,respectively,and improved the inflammation induced by T2DM.These results suggest that low-dose blended tea has hypoglycemic potential,which may be related to lipid-lowering,anti-inflammatory,impaired glucose tolerance,insulin resistance and improvement of islet function.（4）Low-dose blended tea can significantly improve liver injury in T2DM mice.Compared with T2DM model group,liver/body ratio and liver function indexes ALT,AST and TBA in low-dose blended tea group were decreased by 60.34%,47.44%and 80.38%,respectively,effectively reduced liver injury;Liver pathological section showed that low dose blended tea significantly improved liver fat infiltration and inflammatory infiltration.The contents of TC and TG in liver of low dose blended tea group decreased by 61.39%and 48.85%,respectively,reduced the liver lipid disorder;The activities of SOD and CAT in liver of low-dose blended tea group increased by 57.10%and 67.32%,and the content of MDA decreased by 51.42%,reduced liver lipid oxidative damage;The content of liver glycogen in low-dose blended tea group increased by 196.46%,indicating partial recovery of liver function.These results indicate that low-dose blended tea has the potential of liver protection,mainly in alleviating the metabolic burden,lipid oxidative damage,inflammatory infiltration and lipid deposition of the damaged liver.（5）Low-dose blended tea can significantly improve intestinal microflora imbalance in T2DM mice.Compared with T2DM model group,low-dose blended tea extract improved the intestinal microflora disorder caused by T2DM,mainly restoring the composition and structure of intestinal microflora in T2DM mice,and significantly increasing the relative abundance of beneficial microflora（P<0.05）.Low-dose tea extract significantly reduced the increase in the abundance of Spirochaetes and Actinobacteria induced by T2DM.In addition,low-dose blended tea extract induced a significant increase in beneficial bacteria producing short-chain fatty acids（P<0.05）,Such as Ruminococcaceae＿UCG-005,Butyricimonas,Roseburia,Oscillibacter,[Eubacterium]＿nodatum＿group,Muribaculaceae,Prevotellaceae UCG 001.（6）Low-dose blended tea can inhibit the expression of FATP5 in liver of T2DM mice.T2DM significantly up-regulated the expression of fatty acid transporter 5（FATP5）in liver（P<0.05）,and there was no significant difference in the expression of fatty acid transporter 2（FATP2）compared with the control group.Immunohistochemistry and q RT-PCR results showed that FATP5 expression decreased significantly after the intervention of low-dose blended tea extract（P<0.05）.In conclusion,low-dose blended tea may reduce hepatic fatty acid uptake and ultimately reduce hepatic fat accumulation by inhibiting the expression of hepatic FATP5.Collectively,our studies uncovered an ameliorative effect of low-dose blended tea on glycolipid metabolism disorders,liver injury and gut microbiota dysbiosis induced by T2DM.The alleviation of glucose and lipid metabolism in T2DM mice by low-dose blended tea administration may be related to recovery liver function and gut microbiota.Low-dose blended tea may be an effective dietary supplement for preventing T2DM with liver disease,and may providing a rational basis for the development of related foods.