Exploring the Antidiabetic Potential of Heterophylliin A From <i>Elaeocarpus grandis</i>

The antidiabetic efficacy of Elaeocarpus grandis, belonging to the Family Elaeocarpaceae, was investigated using the streptozotocin-induced hyperglycemia model. The ethyl acetate and petroleum ether fractions demonstrated a notable hypoglycemic impact in a rat model of type 2 diabetes mellitus (T2DM), compared to the negative control group. The chemical assessment of these fractions resulted in the isolation and identification of six known compounds (17-22). LC-HR-ESI-MS metabolomic profiling yielded the provisional identification of sixteen metabolites (1-16) across various chemical classes. In silico investigations, encompassing molecular docking and dynamics simulations, indicated that the compounds heterophylliin A (22), as well as habbemine A (12) and elaeocarpinoside (15), can interact with critical enzymes implicated in glucose metabolism, specifically dipeptidyl peptidase-IV and aldose reductase. Moreover, heterophylliin A (22) markedly decreased the expression of inflammatory markers (IL-1β, TNF-α, IL-6, and TGF-β) in diabetic rats. These findings prompt additional research on E. grandis, specifically its bioactive constituent heterophylliin A, which exhibits intriguing antidiabetic effects and warrants further exploration as a potential treatment agent for T2DM.