Tsaokopyranols A-M, 2,6-epoxydiarylheptanoids from Amomum tsao-ko and their α-glucosidase inhibitory activity.

The dried fruits of Amomum tsao-ko are well-known dietary spices and traditional Chinese medicines. The random screen revealed that 50% ethanol-water extract of A. tsao-ko demonstrated significant α-glucosidase inhibitory activity with an IC50 value of 38.6 μg/mL. Bioactivity-guided isolation on the active fraction afforded 13 new 2,6-epoxy diarylheptanoids, tsaokopyranols A-M (1-13), and four known ones (14-17). Their structures featuring a 2,6-epoxy pyran ring were established by extensively spectroscopic analyses (HRESIMS, IR, UV, 1D and 2D NMR) and ECD calculations. Seven new (4-6, 8-11) and one known (16) compounds showed obvious α-glucosidase inhibitory activity with IC50 values ranging from 59.4 to 116.5 μM, higher than acarbose (IC50: 219.0 μM). An enzyme kinetic analysis indicated that compounds 12 and 13 were noncompetitive-type inhibitors of α-glucosidase with Ki values of 539.6 and 385.2 μM. This result provided new insights for the usage of A. tsao-ko, and 2,6-epoxydiarylheptanoids as new anti-diabetic candidates.