Mesua ferrea L. is used in Ayurvedic and Thai medicine for treating various diseases, including diabetes. This study aimed to isolate and identify the bioactive constituents from M. ferrea leaves with potential α-glucosidase inhibitory activity using a bioassay-guided fractionation approach. From the ethyl acetate fraction with the most potent inhibitory effect, we isolated eight polyphenols, including six coumarins (1-6) and two flavonoids (7-8). Notably, five compounds (1, 2, 4, 6, and 8) displayed significant α-glucosidase inhibitory activity with IC50 value ranging from 1.81 to 42.97 µM. Quercetin 3-O-(3″,4″-di-E-p-coumaroyl)-α-L-rhamnoside (8) and mammea A/AA cyclo D (6) were identified as potent α-glucosidase inhibitors, with IC50 value of 1.81 ± 0.12 µM and 6.69 ± 0.27 µM, respectively, surpassing that of the positive control, quercetin (IC50 = 7.82 ± 0.21 µM). Furthermore, mammea A/AA (3) and mammea A/AB (4) exhibited a dual effect by inhibiting α-glucosidase and promoting glucose uptake in 3T3-L1 adipocytes, indicating in developing multi-targeted antidiabetic therapeutics. These findings demonstrated the potential of M. ferrea leaves as a source of novel antidiabetic agents.
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