Dual Inhibitory Activity of Diospyros blancoi A. DC. Leaf Extracts Against Alpha-glucosidase and Butyrylcholinesterase

Diabetes of the brain or type 3 diabetes (T3D) was coined based on evidence of increased risk for developing Alzheimer’s disease due to poor blood glucose regulation. Thus, therapeutics targeting both disease indications may help address T3D. In this study, in vitro bioassay-guided fractionation identified extracts from Diospyros blancoi A. DC leaves with bifunctional inhibition of alpha-glucosidase (AG) and butyrylcholinesterase (BuChE). Screening at 10 µg/mL revealed three column fractions from the ethyl acetate extract with dual inhibitory effects against AG and BuChE, with fraction EV10 being the most potent. EV9 and EV10 were further shown to yield lower IC50 values compared to known reference inhibitors of both enzymes. LC-MS/MS-based identification of phytoconstituents aided by cloud-based bioinformatics was used to rationalize the bioactivities observed. The excellent inhibitory property of D. blancoi against AG and BuChE suggests its potential as a source of bioactive compounds against T3D and related neurodegenerative disorders.