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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line
-
Chemical Fractionation
-
Enzyme Inhibitors / pharmacology*
-
Granulocytes / drug effects
-
Granulocytes / metabolism
-
Guaiacol / analogs & derivatives
-
Guaiacol / analysis
-
Guaiacol / pharmacology
-
Inhibitory Concentration 50
-
Lignans / analysis
-
Lignans / pharmacology*
-
Mice
-
Myristica* / chemistry
-
Phosphorylation / drug effects
-
Plant Extracts / chemistry
-
Plant Extracts / pharmacology
-
Pollen* / chemistry
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1
-
Protein Tyrosine Phosphatases / antagonists & inhibitors*
-
Receptor, Insulin / drug effects
-
Receptor, Insulin / metabolism
Substances
-
Enzyme Inhibitors
-
Lignans
-
Plant Extracts
-
dihydroguaiaretic acid
-
Guaiacol
-
Receptor, Insulin
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1
-
Protein Tyrosine Phosphatases
-
Ptpn1 protein, mouse