Sesquiterpenoids from Alpinia oxyphylla with GLP-1 Stimulative Effects through Ca 2+ /CaMKII and PKA Pathways and Multiple-Enzyme Inhibition.

Six new sesquiterpenoids (-), a pair of enantiomers ( and ), and six known ones (-) were isolated from the fruits of . The structures of the new compounds were elucidated by extensive spectroscopic data and ECD calculations. The stereochemistry of and was reported for the first time. All compounds showed significant GLP-1 stimulation in NCI-H716 cells with promoting ratios ranging from 90.4 to 668.9% at 50 μM. Mechanism study indicated that compound stimulated GLP-1 secretion mainly by regulating the transcription and the shearing process of proglucagon, while compound exerted its effects through up-regulating levels. Interestingly, the GLP-1 stimulative effects of and were both closely related with Ca/CaMKII and PKA pathways but irrelevant to TGR5 and GPR119 receptors. Moreover, most compounds exhibited inhibitory activity against α-glucosidase and PTP1B at concentrations of 100 and 200 μM, while showing no activity against GPa. Compounds , , , and could suppress α-glucosidase with IC values of 190.0, 204.0, 181.8, and 159.6 μM, equivalent to acarbose (IC = 212.0 μM). This study manifests that contains diverse sesquiterpenoids with multiple activities.