Dimeric styrylpyrones with stimulating GLP-1 secretion activities from Alpinia kwangsiensis

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 μM. 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. [Display omitted] •Six dimeric styrylpyrones were obtained from Alpinia kwangsiensis rhizomes.•Alpingsins A and B were elucidated as rare new degraded dimeric styrylpyrones.•Plausible biosynthesis pathway for isolates was speculated.•(+)-Alpingsin A significantly increased GLP-1 secretion (EC50 = 6.51 μM).