TY  - EJOU
AU  - Wang, Yun 
AU  - Li, Xin-Yu 
AU  - Wu, Sheng-Li 
AU  - Gongpan, Pianchou 
AU  - Li, Da-Hong 
AU  - Geng, Chang-An 

TI  - Hypoglycemic Lignans from <i>Amomum tsao-ko</i> Leaves: Their <b><i>α</i></b>-Glucosidase Inhibitory Mechanism Integrated <i>In Silico</i> and <i>In Vivo</i> Validation
T2  - Phyton-International Journal of Experimental Botany

PY  - 2025
VL  - 94
IS  - 8
SN  - 1851-5657

AB  - Twelve lignans (<b>1–12</b>) isolated from <i>Amomum tsao-ko</i> leaves were evaluated for the inhibitory effects against <i>α</i>-glucosidase and PTP1B. Compounds <b>1−4</b> and <b>10</b> showed inhibition on <i>α</i>-glucosidase with inhibitory ratios ranging from 53.8% to 90.0%, while compound <b>10</b> demonstrated 56.1% inhibition on PTP1B at 200 μM. Notably, <i>erythro</i>-5-methoxy-dadahol A (<b>2</b>) and <i>threo</i>-5-methoxy-dadahol A (<b>3</b>) displayed obvious inhibition on <i>α</i>-glucosidase with IC<sub>50</sub> values of 33.3 μM and 22.1 μM, significantly outperforming acarbose (IC<sub>50</sub> = 344.0 μM). Kinetic study revealed that compound <b>3</b> maintained a mixed-type mode, engaging with both free enzyme and enzyme-substrate complex via non-competitive and uncompetitive mechanisms. Molecular docking simulations further clarified its interactions with the key residues of Trp402, Lys400, and Gly361 in the catalytic pocket. <i>In vivo</i> evaluation demonstrated that oryzativol A (<b>1</b>) showed dose-dependent hypoglycemic effects in an oral starch tolerance test, reducing postprandial blood glucose levels (<i>AUC</i>) by 21.1% (20 mg/kg) and 24.9% (40 mg/kg). These results highlight the potential of lignans in <i>A. tsao-ko</i> as <i>α</i>-glucosidase inhibitors for managing type 2 diabetes, warranting further exploration of their therapeutic potential.
KW  - Lignans; <i>α</i>-glucosidase inhibitors; enzyme kinetics; <i>Amomum tsao-ko</i>; oral starch tolerance test

DO  - 10.32604/phyton.2025.068185