Comprehensive Bioactivity-Guided Isolation, DeepSAT, and LC-Q-TOF-MS/MS Analysis to Reveal Hypoglycemic Constituents...

Activation of intestinal bitter taste receptors can stimulate the release of glucagon-like peptide-1 (GLP-1), thereby enhancing insulin secretion and exerting a hypoglycemic effect. In this study, a combination of bioactivity-guided screening and chemical analysis was applied to search for potential components from Momordica charantia L. that exert hypoglycemic effects via bitter taste receptors. Combined with molecular networking and DeepSAT analysis, the active fraction was found to be rich in cucurbitane-type triterpenoids, from which five pure compounds were isolated and identified. In conjunction with LC-Q-TOF-MS/MS analysis, an additional 24 cucurbitane-type triterpenoids were also identified from the active fraction. Bioactivity evaluation revealed that five compounds exhibited stimulatory effects on GLP-1 secretion in Caco-2 cells; Compounds 2 and 4 increased GLP-1 secretion to 1.40-fold and 1.35-fold of the basal level at 5 µM, respectively. These results indicate that cucurbitane-type triterpenoids may responsible for the potential hypoglycemic effect of M. charantia L. via bitter taste receptors. PRACTICAL APPLICATIONS: Cucurbitane-type triterpenoids derived from M. charantia L. are capable of stimulating the secretion of GLP-1 in intestinal cells, indicating their potential hypoglycemic activity. These compounds are promising as natural bioactive substances for the development of functional foods aimed at blood glucose homeostasis regulation. Furthermore, this provides a valuable research direction for the screening of natural hypoglycemic agents based on bitter taste receptors.