Haoshu Liu, Hairong Xiang, Huannan Li, Ruyu Jiang, Yue Zhang, Linfeng Zhao, Dawei Zeng, Jiazhen Xie, Yanju Gong, Xiongbin Chen, Lan Yang
α-Glucosidase inhibitors play a role in postprandial blood glucose. However, synthetic hypoglycemic drugs often cause gastrointestinal discomfort and are unsuitable for use as food additives. Natural compounds from plants have therefore attracted interest as safer candidates for hypoglycemic functional foods. Vincoside lactam (VCS-LT), an indole alkaloid isolated from the leaves of Uncaria rhynchophylla (Miq.) Miq. ex Havil., is traditionally used in East Asian herbal teas and dietary supplements. We evaluated its carbohydrate-digestion inhibitory activity to provide experimental evidence for the development of herbal beverages and grain supplements with hypoglycemic properties. The in vitro assay used yeast-derived α-glucosidase, whereas the molecular docking targeted human maltase-glucoamylase (MGAM)-a distinction that is important for interpreting the respective findings. Molecular docking indicated the stable binding of VCS-LT to two catalytic domains of maltase-glucoamylase, a key intestinal enzyme involved in reducing postprandial glucose excursion after maltose loading following the consumption of high-carbohydrate staple foods. In a p-nitrophenyl-α-D-glucopyranoside-based assay using yeast-derived α-glucosidase, VCS-LT showed potent inhibitory activity. In alloxan-induced diabetic mice, oral VCS-LT reduced fasting glucose and attenuated postprandial spikes after maltose loading. In contrast to the gastrointestinal side effects commonly associated with synthetic α-glucosidase inhibitors such as acarbose, no gastrointestinal discomfort or other adverse effects were observed during the 12-day administration period. Collectively, our findings demonstrate that VCS-LT is a potent food-derived α-glucosidase inhibitor that effectively attenuates postprandial glucose excursion in diabetic mice, which supports its potential application as a functional food ingredient for daily dietary glycemic management. Nevertheless, our work remains at the proof-of-concept level, and future studies on processing stability, bioaccessibility, food-matrix interactions, sensory acceptability, and safety at food-use levels are essential before any commercial application can be envisioned.