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

IF 2.5 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia Pub Date : 2025-04-23 DOI:10.1016/j.fitote.2025.106566

Yun Wang , Xin-Yu Li , Sheng-Li Wu , Pianchou Gongpan , Yi Yang , Mei Huang , Da-Hong Li , Chang-An Geng

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Abstract

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 (IC₅₀ = 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.

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草果砂叶抗糖尿病二芳基庚烷及其对α-葡萄糖苷酶的抑制机制

从菰叶中分离出了 13 种二芳基庚烷类化合物，其中包括 4 种未曾描述过的化合物（1-4）。化合物 1 和 2 是两种不同寻常的二芳基庚烷类-苯丙氨酯混合物。对其中几种分离物进行了生物活性测试，以确定它们在促进 GLP-1 分泌和抑制多种 2 型糖尿病相关酶方面的活性。2-Hydroxymusaitinerin A (1) 对 GPa、PTP1B 和 α-葡萄糖苷酶具有广泛的抑制活性，在 200 μM 时抑制率分别为 99.0 %、59.4 % 和 55.9 %。酶动力学研究表明，Platyphyllone（12）是α-葡萄糖苷酶的混合型抑制剂（IC50 = 25.8 μM），通过非竞争和反竞争两种模式抑制该酶。荧光淬灭试验证实，化合物 12 直接与 α-葡萄糖苷酶相互作用，通过单一结合位点形成基础复合物。分子对接预测了 12 的 OH-4′′、OH-5 和 3-羰基与 α-葡萄糖苷酶之间的氢键相互作用。这项研究表明，苤蓝叶是具有多酶抑制作用的二芳基庚酸类化合物的丰富来源。

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来源期刊

Fitoterapia 医学-药学

CiteScore

5.80

自引率

2.90%

发文量

198

审稿时长

1.5 months

期刊介绍： Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.