Studies On The Action And Mechanism Of Desmethylebellidifolin Promoting The Proliferation Of Islet β Cells By Inhibiting DYRK1A

Dual substrate specific tyrosine phosphorylation regulated kinase A(DYRK1A),which located in the key region of human chromosome 21,plays a key role in Down syndrome,Alzheimer’s disease,pancreatic cancer and diabetes.The researchs show that inhibiting the phosphorylation of dual substrate specific tyrosine phosphorylation regulated kinase A can induce the proliferation of islet β cells,this target is considered to be a potential target for the treatment of diabetes.Our previous study found that desmethylbellidifolin(DMB)is a highly effective DYRK1 A inhibitor to induce the proliferation of islet β cells,and has good activity in vitro.Based on the previous work,we use the means of X-ray crystallography to analysis the co-crystal structure of DYRK1 A and DMB,elucidate the mechanism of DYRK1 A inhibition at the atomic level.We tested and verified this result in cell level and by Gene expression profile.It was proved that DMB could affect TGF β pathway in INS-1 cell.As an effective natural small molecule inhibitor of DYRK1 A,DMB has the advantages of low toxicity and good activity compared with the existing lead compounds.It can be used as a clinical candidate drug for the treatment of diabetes,and has good development and research value.