Antidiabetic diarylheptanoids from the leaves of Amomum tsao-ko and their inhibition mechanism against α-glucosidase.

Thirteen diarylheptanoids, including four undescribed ones (1-4), were isolated from the leaves of Amomum tsao-ko. Compounds 1 and 2 are two unusual diarylheptanoid-phenylpropanoid hybrids. Several of the isolates were tested for their biological activity in promoting GLP-1 secretion and inhibiting multiple type 2 diabetes-related enzymes. 2-Hydroxymusaitinerin A (1) demonstrated broad inhibitory activity against GPa, PTP1B and α-glucosidase with inhibition rates of 99.0 %, 59.4 % and 55.9 %, respectively at 200 μM. Platyphyllone (12) is a mixed-type inhibitor of α-glucosidase (IC = 25.8 μM), inhibiting the enzyme through both non-competitive and anti-competitive modes, as shown by enzyme kinetic study. Fluorescence quenching test confirmed that compound 12 directly interacted with α-glucosidase, forming a basal complex via a single binding site. Molecular docking predicted hydrogen-bonding interactions between OH-4'', OH-5 and 3‑carbonyl groups of 12 and α-glucosidase. This study highlights that the leaves of Amomum tsao-ko are a rich source of diarylheptanoids with multi-enzyme inhibitory effects.