| Title | Dimeric styrylpyrones with stimulating GLP-1 secretion activities from Alpinia kwangsiensis |
| Author | Wu, Meng-Zhen |
| Publication | TETRAHEDRON |
| Year | 2022 |
| Volume | 120 |
| Corresponding Author | Ji, KL;Sun, YL |
| Abstract | Stimulating glucagon-like peptide-1 (GLP-1) secretion is an important approach for the treatment of type 2 diabetes. Chemical investigation of Alpinia kwangsiensis rhizomes produced six dimeric styrylpyrones (1-6), including two new degraded ones (1 and 2). Compounds 1-4 were identified as four pairs of enantiomers and successfully prepared by chiral HPLC separation. These compounds incorporate the distinctive cyclobutane moiety via [2 + 2] cycloaddition, a key step in the biosynthetic pathway. The bioactivities of isolates in stimulating GLP-1 secretion in STC-1 cells were evaluated. Results showed that compounds (+)-1, (+)-2, (-)-2, (-)-4, 5 and 6 significantly increased GLP-1 secretion, and compound (+)-1 exhibited the strongest activity with EC50 value of 6.51 mM. In addition, compounds (+)-2, (-)-4 and 5 promoted GLP-1 secretion by increasing intracellular calcium concentration dependent on the PKA pathway, which could provide a chemical basis for the development of diabetes drugs especially that directly promote GLP-1 secretion. |
