Li Qian, Yang Zhangchang, Lu Huijie, Liu Fan, Zhou Donglai, Zou Yuxiao
Sericultural & Agri-Food Research Institute, Guangdong Academy of Agricultural Sciences, Key Laboratory of Functional Foods, Ministry of Agriculture and Rural Affairs, Guangdong Key Laboratory of Agricultural Products Processing, Guangzhou 510610, China.
Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China.
Nutrients. 2025 Jan 23;17(3):406. doi: 10.3390/nu17030406.
The hypoglycemic activity of mulberry leaf polyphenols has been widely studied, while its mechanism of action needs further elucidation.
The inhibitory activity mechanism of astragalin on α-glucosidase was investigated with a combination of multispectroscopic techniques and molecular docking. The hypoglycemic pathway was further revealed with a high-glucose human hepatocellular carcinomas (HepG2) cell model.
The results indicated that astragalin inhibited α-glucosidase with IC of 154.5 µM, which was the highest in potency among the main polyphenols from mulberry leaves. Astragalin could bind to α-glucosidase with a single inhibition site and quench its endofluorescence with a static quenching mechanism. Astragalin changed the secondary structure of α-glucosidase, and the decreased α-helix content, representing the un-folding conformation, resulted in the decreased activity. The molecular docking further indicated that two sustainable hydrogen bonds were generated between astragalin and α-glucosidase residue Ser-88 and Tyr-133. The main driving forces to form the astragalin-α-glucosidase complex were the van der Waals force and hydrogen bond. Astragalin at a concentration of 80 µg/mL obtained the best hypoglycemic effect by activating the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway.
This study provides new insights into the potential utilization of astragalin-rich foods in the improvement of diabetes mellitus.
桑叶多酚的降血糖活性已得到广泛研究，但其作用机制仍需进一步阐明。
采用多种光谱技术和分子对接相结合的方法，研究紫云英苷对α-葡萄糖苷酶的抑制活性机制。通过高糖人肝癌（HepG2）细胞模型进一步揭示其降血糖途径。
结果表明，紫云英苷对α-葡萄糖苷酶具有抑制作用，IC为154.5 μM，是桑叶主要多酚中活性最高的。紫云英苷可与α-葡萄糖苷酶结合于单一抑制位点，并通过静态猝灭机制猝灭其内源荧光。紫云英苷改变了α-葡萄糖苷酶的二级结构，α-螺旋含量降低，代表未折叠构象，导致活性降低。分子对接进一步表明，紫云英苷与α-葡萄糖苷酶残基Ser-88和Tyr-133之间形成了两个稳定的氢键。形成紫云英苷-α-葡萄糖苷酶复合物的主要驱动力是范德华力和氢键。浓度为80 μg/mL的紫云英苷通过激活5'-单磷酸腺苷（AMP）激活的蛋白激酶（AMPK）信号通路获得最佳降血糖效果。
本研究为富含紫云英苷的食物在改善糖尿病方面的潜在应用提供了新的见解。
