Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a therapy for treatment of type 2 diabetes and obesity. Bioassay-guided fractionation of the MeOH extract of the leaves and stems of Symplocos paniculata (Thunb.) Miq. (Symplocaceae), using an in vitro PTP1B inhibitory assay, resulted in the isolation of three ursane-type triterpenes, ursolic acid (1), corosolic acid (2) and 2alpha,3alpha,19alpha,23-tetrahydroxyurs-12-en-28-oic acid (3). Compounds 1-3 inhibited PTP1B with IC (50) values of 3.8 +/- 0.5, 7.2 +/- 0.8 and 42.1 +/- 1.5 microM, respectively. Kinetic studies suggest that 1 is a competitive inhibitor with a K(i) value of 2.0 microM, whereas 2 is a mixed-type inhibitor of PTP1B. Our results indicate that the substitution of hydroxy groups on the ursane-type triterpenes is responsible for the loss of activity, and thus 1 and 2 possessing only one or two hydroxy groups can be potential PTP1B inhibitors.