New diarylheptanoid dimers as GLP-1 secretagogues and multiple-enzyme inhibitors from Alpinia katsumadai

Ten new diarylheptanoid dimers, katsumadainols C-1 - C-10 (1-10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, alpha-glucosidase, PTP1B, and DPP4. Compounds 1-5 and 7-10 significantly stimulated GLP-1 secretion by 267.5-433.1% (25.0 mu M) and 117.8-348.2% (12.5 mu M). Compounds 1-4 exhibited significant inhibition on GPa with IC50 values of 18.0-31.3 mu M; compounds 1-5 showed obvious inhibition on alpha-glucosidase with IC50 values of 6.9-18.2 mu M; compounds 1-5 and 10 possessed PTP1B inhibitory activity with IC50 values ranging from 35.5 to 80.1 mu M. This investigation first disclosed compounds 1-4 as intriguing GLP-1 secretagogues and GPa, alpha-glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants.