Identified prenylated polyphenols from Mesua ferrea L. and their stimulatory effect on glucose uptake in 3 T3-L1 adipocytes.

Mesua ferrea L. has traditionally utilized in folk medicine for its antidiabetic properties, and contemporary pharmacological studies have confirmed its hypoglycemic activity. While, the specific components responsible for these effects have not yet been fully elucidated. In this study, we employed a bioactivity-guided fractionation approach to isolate 22 prenylated polyphenols from M. ferrea leaves, including two novel 4-phenylcoumarins, mesuol A (1) and mesuol B (2), along with 20 previously identified compounds. The majority of these compounds, including 13 4-phenylcoumarins and two xanthones, exhibited significant stimulatory effect on glucose uptake in 3 T3-L1 adipocytes. Notably, at a concentration of 2 μM, isomesuol (14), disparinol D (17), and isodisparinol A (19) exhibited glucose uptake stimulatory effect that were either superior or equivalent to that of insulin (positive control). The structure-activity relationship analysis revealed that cyclization of 4-phenylcoumarins to form a furan ring markedly diminished their glucose uptake stimulatory effects, thereby reducing their hypoglycemic potential. In contrast, non-cyclized and pyran ring-cyclized 4-phenylcoumarins demonstrated stronger glucose uptake-stimulatory activities. These findings highlight the non-cyclized and pyran ring-cyclized 4-phenylcoumarins as promising leads for the development of anti-diabetic agents, with M. ferrea leaves serving as a valuable source of these bioactive compounds.