Wang Yi, Lan Suqing, Zhang Laiming, Li Yunxuan, Deng Ziyang, Ye Xingqian, Pan Haibo, Chen Shiguo
College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Zhejiang University, Hangzhou, PR China.
Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, PR China.
Mol Nutr Food Res. 2025 May;69(9):e202400838. doi: 10.1002/mnfr.202400838. Epub 2025 Mar 19.
Polyphenols reportedly possess strong in vitro α-glucosidase inhibitory activity, even higher than acarbose, but their in vivo regulation on postprandial hyperglycemia is poor. So far this typical problem of polyphenols remains unsolved, greatly hindering their application as α-glucosidase inhibitors.
Here, we identify the small intestinal mucus layer acts as a barrier to significantly reduce in vivo α-glucosidase inhibitory activity of epigallocatechin gallate, prodelphinidin B digallate (proDB DG), and proanthocyanidins from Chinese bayberry leaves. Multispectroscopy, rheology, solvent method, and molecular docking analysis showed that these pyrogallol-based polyphenols, especially proDB DG strongly interacted with small intestinal mucins through hydrogen bonding, hydrophobic interactions, and electrostatic interactions. These interactions block polyphenols from penetrating the mucus layer, resulting in their low binding rates with α-glucosidase in vivo. Besides, polyphenol-driven aggregation of the mucins enhanced the barrier function and reduced the permeability of the mucus layer, resulting in delayed digestion and absorption of carbohydrates.
The mucus barrier weakens the inhibitory activity of pyrogallol-based polyphenols against α-glucosidase. Hence, overcoming the mucus barrier is a promising strategy to improve the regulation of pyrogallol-based polyphenols against postprandial hyperglycemia in vivo, which helps them to become novel α-glucosidase inhibitors in the clinic.
据报道，多酚具有很强的体外α-葡萄糖苷酶抑制活性，甚至高于阿卡波糖，但其对餐后高血糖的体内调节作用较差。迄今为止，多酚的这一典型问题仍未解决，极大地阻碍了它们作为α-葡萄糖苷酶抑制剂的应用。
在此，我们发现小肠黏液层作为一种屏障，可显著降低表没食子儿茶素没食子酸酯、原花色素B二没食子酸酯（原花色素B3）以及杨梅叶原花青素在体内的α-葡萄糖苷酶抑制活性。多光谱学、流变学、溶剂法和分子对接分析表明，这些基于邻苯三酚的多酚，尤其是原花色素B3，通过氢键、疏水相互作用和静电相互作用与小肠黏蛋白强烈相互作用。这些相互作用阻止多酚穿透黏液层，导致它们在体内与α-葡萄糖苷酶的结合率较低。此外，多酚驱动的黏蛋白聚集增强了屏障功能，降低了黏液层的通透性，导致碳水化合物的消化和吸收延迟。
黏液屏障削弱了基于邻苯三酚的多酚对α-葡萄糖苷酶的抑制活性。因此，克服黏液屏障是改善基于邻苯三酚的多酚对体内餐后高血糖调节作用的一种有前景的策略，这有助于它们成为临床上新型的α-葡萄糖苷酶抑制剂。
