title: Inhibition of protein tyrosine phosphatase 1B by lignans from Myristica fragrans.
abstract: Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as one of the drug targets for treating type 2 diabetes and obesity. Bioassay-guided fractionation of a MeOH extract of the semen of Myristica fragrans Houtt. (Myristicaceae) afforded PTP1B inhibitory compounds, meso-dihydroguaiaretic acid (1) and otobaphenol (2). Compounds 1 and 2 inhibited PTP1B with IC(50) values of 19.6 +/- 0.3 and 48.9 +/- 0.5 microM, respectively, in the manner of non-competitive inhibitors. Treatment with compound 1 on 32D cells overexpressing the insulin receptor (IR) resulted in a dose-dependent increase in the tyrosine phosphorylation of IR. These results indicate that compound 1 can act as an enhancing agent in intracellular insulin signaling, possibly through the inhibition of PTP1B activity.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Eoeun-dong, Yusong-gu, Daejeon 305-333, Korea.
authors.forename: Senugmi
authors.initials: S
authors.lastname: Yang
authors.forename: Min Kyun
authors.initials: MK
authors.lastname: Na
authors.forename: Jun Pil
authors.initials: JP
authors.lastname: Jang
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Kim
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Nak Ju
authors.initials: NJ
authors.lastname: Sung
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002460:Cell Line; D005591:Chemical Fractionation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006139:Guaiacol / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000032:analysis / Q000494:pharmacology*; D051379:Mice; D026323:Myristica / Q000737:chemistry; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011058:Pollen / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D017705:Lignans; D010936:Plant Extracts; C015816:dihydroguaiaretic acid; D006139:Guaiacol; D011972:Receptor, Insulin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse