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

[Display omitted] • Ten new diarylheptanoid dimers were isolated from A. katsumadai. • Compounds 1 – 5 and 7 – 10 significantly stimulated GLP-1 secretion. • Compounds 1 – 4 showed obvious inhibition on GPa. • Compounds 1 – 5 and 10 were PTP1B selective inhibitors. • Compounds 1 – 4 were GLP-1 secretagogues and multiple-enzyme inhibitors. 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, α -glucosidase, PTP1B, and DPP4. Compounds 1 – 5 and 7 – 10 significantly stimulated GLP-1 secretion by 267.5–433.1% (25.0 μM) and 117.8–348.2% (12.5 μM). Compounds 1 – 4 exhibited significant inhibition on GPa with IC 50 values of 18.0–31.3 μM; compounds 1 – 5 showed obvious inhibition on α -glucosidase with IC 50 values of 6.9–18.2 μM; compounds 1 – 5 and 10 possessed PTP1B inhibitory activity with IC 50 values ranging from 35.5 to 80.1 μM. This investigation first disclosed compounds 1 – 4 as intriguing GLP-1 secretagogues and GPa, α -glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants. [ABSTRACT FROM AUTHOR]