PTP1B inhibitory effect of abietane diterpenes isolated from Salvia miltiorrhiza

Biol Pharm Bull. 2005 Sep;28(9):1795-7. doi: 10.1248/bpb.28.1795.

Abstract

Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling, and selective inhibition of PTP1B has served as a potential drug target for the treatment of type 2 diabetes. In the course of screening for PTP1B inhibitory natural products, the MeOH extract of the dried root of Salvia miltiorrhiza BUNGE (Labiatae) was found to exhibit significant inhibitory effect. Bioassay-guided fractionation and purification afforded three related abietane-type diterpene metabolites 1-3. Compounds 1-3 were identified as isotanshinone IIA (1), dihydroisotanshinone I (2), and isocryptotanshinone (3) mainly by analysis of NMR and MS data. Compounds 1-3 non-competitively inhibited PTP1B activity with 50% inhibitory concentration values of 11.4+/-0.6 microM, 22.4+/-0.6 microM and 56.1+/-6.3 microM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / chemistry
  • Abietanes / isolation & purification
  • Abietanes / pharmacology*
  • Hydrolysis
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Plant Roots / chemistry
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Salvia / chemistry*

Substances

  • Abietanes
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases