Establishment Of DPPIV-and GAA-based Screening Model For Anti-diabetes And Their Application In Uyghur Medical Herbs Extracts

Diabetes mellitus is one of metabolic disorders with hyperglycemia.Hyperglycemia affects the function of pancreatic beta cells, results to lack of insulinor insulin resistance, and loss of the function of beta cell. Complication ofdiabetes is the main factors influencing the physical health. The important precautionsfor preventing complication were controlling the level of blood glucose.The project is focusing on type II diabetes and applying DPPIV, PTPIB and GAAbased screening system for anti-diabetes to screen anti-diabetic ingredients fromcharacteristic plant of Xinjiang.Recent years, DPPIV(Dipeptidyl peptidase) is one of hot targets for treatingdiabetes. DPPIV can degrade GLP-1and GIF. So, the inhibition of DPPIV couldimprove the activity of GLP-1and GIP, which result in lowing the level of bloodglucose. The study was establishment of DPPIV-based screening model foranti-diabetes with37。C of reaction temperature,30min of reaction time, and0.064mg/mL of contraction of substrate.18extracts from blackcurrant and sparsifolia werescreened by this model. The results showed that BL2and BL5ingredient ofblackcurrant could inhibit the activity of DPPIV and their IC50were133.43)ig/mLand148.75)ig/mL seperately.GA A (a-glue OS i das e) is an enzyme involved in regulation of postprandial glucose.Inhibitors of GAA can reduce the activity of DPPIV resulting to lowing the level ofblood glucose through effectively prevent polysaccharide degradation tomonosaccharide. In this study, the cell model aiming to GAA was set up to screeningthe inhibition of extracts from the plant of Xinjiang on GAA. The results showed thatthe extract of pomegranate flower and BF2ingredient of blackcurrant couldeffectively inhibit the activity of GAA, and their IC50were separately0.887mg/mL,0.67mg/mL.PTPlB(Protein tyrosine phosphatase-IB) is one of new drug targets against insulinsensitizer and negatively regulate the insulin signaling pathway. Inhibition of PTPIBcould improve sensitivity of insulin and effectively regulate the level of blood glucose.In this study, first, The effect of BF2, extract of pomegranate flower and extract of Flos rosae Rugosae on PTPIB activity was observed by recombinant PTPIBinhibition method, and their IC50is separately7.25)ig/mL、102.23ng/mL and62.31ng/mL. Second, the effect of them above on glucose consumption were observed invitro, and the results showed that they could enhance consumption of glucose. Finally,anti-diabetic mechanisms of the3inhibitors above in CHO-Kl and L6cell wereresearched. The results showed that they could affect phosphorylation of Ins-1、PDKl、AKT、GSK-3pin insulin signaling pathway. Phosphorylation of Ins-1couldregulate the activity of AKT by activating PI3K, and phosphorylation of itsdownstream PDKl. And active AKT also enhanced phosphorylation of GSK-3p,which improved the synthesis of glycogen. And on the other hand, phosphorylationof AKT could regulate translocation GLU4, which propel output of glucose andmaintain the output dynamic balance of blood glucose.Extracts from the plant can regulate glucose metabolism, not only with low toxicity,more stable characteristics on physiological condition, And also synthesis of morenew structure compound. Pomegranate flowers, rose blackcurrant, alhagi all arecharacteristics of medicinal plants of Xinjiang. They were obtained byphytochemistry methods. Their anti-diabetic ability were study. These research will bebeneficial to rational utilization of Xinjiang plants resource and improve theireconomic value. In short, the study will provide support for further exploration andutilization of Uygur herbs.