An infusion of Orthosiphon aristatus has long been used for diabetes therapy; however, the active principles remained unknown. Herein, we report the identification of the putative agents responsible for this antidiabetic activity using an α-glucosidase-guided isolation. Four flavonoids named sinensetin (1), salvigenin (2), tetramethylscutellarein (3) and 3,7,4′-tri-O-methylkaempferol (4), together with a diterpenoid named orthosiphol A (5), were characterized, based on analysis of their spectroscopic data. Flavonoids 3 and 4 inhibited yeast α-glucosidase with IC50 values of 6.34 and 0.75 mM, respectively, whereas orthosiphol A (5) selectively inhibited intestinal maltase with an IC50 value of 6.54 mM. A kinetic investigation of 5 indicated that it retarded maltase function in a noncompetitive manner.
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