Open Access

ARTICLE

Hypoglycemic Lignans from Amomum tsao-ko Leaves: Their α-Glucosidase Inhibitory Mechanism Integrated In Silico and In Vivo Validation

Yun Wang^1,2,#, Xin-Yu Li^1,3,#, Sheng-Li Wu^1,3, Pianchou Gongpan¹, Da-Hong Li², Chang-An Geng^1,3,*

1 State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
2 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China
3 University of Chinese Academy of Sciences, Beijing, 100049, China

* Corresponding Author: Chang-An Geng. Email:
# These authors contributed equally to this work

Phyton-International Journal of Experimental Botany 2025, 94(8), 2563-2574. https://doi.org/10.32604/phyton.2025.068185

Received 22 May 2025; Accepted 23 July 2025; Issue published 29 August 2025

Abstract

Twelve lignans (1–12) isolated from Amomum tsao-ko leaves were evaluated for the inhibitory effects against α-glucosidase and PTP1B. Compounds 1−4 and 10 showed inhibition on α-glucosidase with inhibitory ratios ranging from 53.8% to 90.0%, while compound 10 demonstrated 56.1% inhibition on PTP1B at 200 μM. Notably, erythro-5-methoxy-dadahol A (2) and threo-5-methoxy-dadahol A (3) displayed obvious inhibition on α-glucosidase with IC₅₀ values of 33.3 μM and 22.1 μM, significantly outperforming acarbose (IC₅₀ = 344.0 μM). Kinetic study revealed that compound 3 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. In vivo evaluation demonstrated that oryzativol A (1) showed dose-dependent hypoglycemic effects in an oral starch tolerance test, reducing postprandial blood glucose levels (AUC) by 21.1% (20 mg/kg) and 24.9% (40 mg/kg). These results highlight the potential of lignans in A. tsao-ko as α-glucosidase inhibitors for managing type 2 diabetes, warranting further exploration of their therapeutic potential.

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Keywords

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