title: PTP1B inhibitory effect of abietane diterpenes isolated from Salvia miltiorrhiza.
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.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Han
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Kim
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Dae Gwin
authors.initials: DG
authors.lastname: Jeong
authors.forename: Seong Eon
authors.initials: SE
authors.lastname: Ryu
authors.forename: Dai-Eun
authors.initials: DE
authors.lastname: Sok
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D018517:Plant Roots / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D027544:Salvia / Q000737:chemistry*
chemical_list: D045784:Abietanes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases