Potential Antidiabetic Activity of Nordihydroguaiaretic Acid: An Insight into Its Inhibitory Mechanisms on Carbohydrate-Hydrolyzing Enzymes, the Binding Behaviors with Enzymes, and <i>In Vivo</i> Antihyperglycemic Effect

The inhibitory mechanisms and binding behaviors of nordihydroguaiaretic acid (NDGA) to α-glucosidase/α-amylase were investigated by <i>in vitro</i> multispectroscopic methods and <i>in silico</i> modeling technique. The results demonstrated that NDGA reversibly and uncompetitively inhibited α-glucosidase, exhibiting stronger inhibition than acarbose, while it displayed noncompetitive inhibition against α-amylase. Additionally, NDGA could spontaneously bind to α-glucosidase/α-amylase mainly through hydrogen bonds and hydrophobic forces, thus altering the spatial structure of enzymes and reducing their catalytic activity. The presence of crowding reagents/polysaccharides/undigested milk proteins would decrease the inhibitory ability of NDGA, whereas fatty acids exhibited the opposite phenomenon on α-glucosidase. Furthermore, the antidiabetic activity of NDGA <i>in vivo</i> was evaluated using the diabetic <i>Drosophila</i> model induced by a high-sugar diet. It was found that NDGA significantly reduced the glucose levels of diabetic <i>Drosophila</i>. These findings suggested that NDGA was a potential inhibitor of α-glucosidase/α-amylase and could be used as a nutritional adjuvant to prevent diabetes.