Hao Zongwei, Li Zhaofeng, Ma Zhenni, Liu Xinran, Shen Zhichao, Ma Yulei, Xu Huajian, Yu Zhenyu, Du Yiqun
National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Anhui Provincial Joint Construction Key Laboratory of Industrial New-Style Tea Beverage Green Manufacturing, Anhui Provincial Key Laboratory of Food Safety Monitoring and Quality Control, School of Food and Nutrition, Anhui Agricultural University, Hefei 230036, China.; Joint Research Center for Food Nutrition and Health of IHM, Anhui Agricultural University, Hefei 230036, China.
Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, College of Food Science, Southwest University, Chongqing 400715, China.
Food Chem. 2025 Oct 1;488:144858. doi: 10.1016/j.foodchem.2025.144858. Epub 2025 May 21.
Natural products are gaining attention as α-glucosidase (α-GLU) inhibitors owing to their safety and multifunctionality. L-theanine (THE) and epigallocatechin gallate (EGCG) in tea have inhibitory effects, but whether their synergistic inhibition of α-GLU remains unclear. This study investigated the synergistic mechanism of THE and EGCG in inhibiting α-GLU activity using spectral analysis and computational simulation. The results showed that a combination of 1.6 mM THE and 0.11 mM EGCG significantly enhanced α-GLU inhibition. Fluorescence quenching experiments revealed that EGCG did not alter the static quenching pattern of THE on α-GLU. However, it promoted enzyme conformational changes. Multi-spectral analysis and molecular dynamics simulations further demonstrated that THE and EGCG interacted non-covalently with key α-GLU residues (ASP-242, PHE-303, and PRO-312, etc.), disrupting the active site structure, reducing its catalytic efficiency. These findings provide valuable insight into the synergistic inhibition of α-GLU by natural active ingredients, with potential applications in functional foods.
天然产物因其安全性和多功能性而作为α-葡萄糖苷酶（α-GLU）抑制剂受到关注。茶中的L-茶氨酸（THE）和表没食子儿茶素没食子酸酯（EGCG）具有抑制作用，但其对α-GLU的协同抑制作用尚不清楚。本研究采用光谱分析和计算模拟方法，研究了THE和EGCG抑制α-GLU活性的协同机制。结果表明，1.6 mM THE和0.11 mM EGCG的组合显著增强了对α-GLU的抑制作用。荧光猝灭实验表明，EGCG没有改变THE对α-GLU的静态猝灭模式。然而，它促进了酶的构象变化。多光谱分析和分子动力学模拟进一步证明，THE和EGCG与α-GLU的关键残基（ASP-242、PHE-303和PRO-312等）非共价相互作用，破坏了活性位点结构，降低了其催化效率。这些发现为天然活性成分对α-GLU的协同抑制作用提供了有价值的见解，在功能性食品中具有潜在应用。
