Promyos Natnicha, Temviriyanukul Piya, Suttisansanee Uthaiwan
Institute of Nutrition, Mahidol University, Phutthamonthon, Nakhon Pathom 73170, Thailand.
Prev Nutr Food Sci. 2020 Sep 30;25(3):263-271. doi: 10.3746/pnf.2020.25.3.263.
Anthocyanidins are bioactive compounds found mostly in colored plants and fruits. Consumption of anthocyanidin-rich foods has been shown to reduce the risk of diabetes. However, limited information is available regarding the inhibitory effect and interactions of anthocyanidins on α-glucosidase, the key enzyme that controls diabetes through degrading carbohydrate. Therefore, we used computational docking analysis to investigate the degree and type of inhibition by α-glucosidase, and the structural interactions of enzyme-selected anthocyanidins. The results suggested that anthocyanidins exhibit half maximal inhibitory concentration of 4∼55 μM; the strongest and weakest α-glucosidase inhibitors were delphinidin and malvidin, respectively. Indeed, delphinidin inhibits α-glucosidase in a mixed type, close to non-competitive manner with an inhibitory constant of 78 nM. Addition of a glycoside (glucoside or galactoside) at C3 on the C ring of delphinidin significantly decreased inhibitory activity, and addition of glycosides at C3 on the C ring and C5 on the A ring of delphinidin prevented all inhibitory activity. Molecular docking and free binding energy accurately confirmed the mode of inhibition determined by enzyme kinetics. These data will inform the use of alternative sources of anthocyanidins in functional foods and dietary supplements for prevention of diabetes. The results provide useful information for evaluating possible molecular models using anthocyanins/anthocyanidins as templates and α-glucosidase as the key enzyme in management of diabetes.
花青素是一类生物活性化合物，主要存在于有色植物和水果中。食用富含花青素的食物已被证明可以降低患糖尿病的风险。然而，关于花青素对α-葡萄糖苷酶（通过降解碳水化合物来控制糖尿病的关键酶）的抑制作用及其相互作用的信息有限。因此，我们使用计算对接分析来研究花青素对α-葡萄糖苷酶的抑制程度和类型，以及酶选择的花青素的结构相互作用。结果表明，花青素的半数最大抑制浓度为4∼55 μM；最强和最弱的α-葡萄糖苷酶抑制剂分别是飞燕草素和锦葵色素。事实上，飞燕草素以混合型抑制α-葡萄糖苷酶，接近非竞争性抑制，抑制常数为78 nM。在飞燕草素C环的C3位添加糖苷（葡萄糖苷或半乳糖苷）会显著降低抑制活性，在飞燕草素C环的C3位和A环的C5位添加糖苷会完全消除所有抑制活性。分子对接和自由结合能准确地证实了酶动力学确定的抑制模式。这些数据将为在功能性食品和膳食补充剂中使用替代来源的花青素预防糖尿病提供参考。这些结果为评估以花青素/花色苷为模板、α-葡萄糖苷酶为糖尿病管理关键酶的可能分子模型提供了有用信息。
