Inhibition of protein tyrosine phosphatase 1B by ursane-type triterpenes isolated from Symplocos paniculata.
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.
Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon.
Minkyun
M
Na
Seungmi
S
Yang
Long
L
He
Hyuncheol
H
Oh
Beom Seok
BS
Kim
Won Keun
WK
Oh
Bo Yeon
BY
Kim
Jong Seog
JS
Ahn
D027901:Acanthaceae; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D009765:Obesity / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D018547:Plant Stems; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000187:drug effects*; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D014315:Triterpenes; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases