PTP1B inhibitory effect of abietane diterpenes isolated from Salvia miltiorrhiza.
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.
Han
Yu Mi
YM
Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
Oh
Hyuncheol
H
Na
MinKyun
M
Kim
Beom Seok
BS
Oh
Won Keun
WK
Kim
Bo Yeon
BY
Jeong
Dae Gwin
DG
Ryu
Seong Eon
SE
Sok
Dai-Eun
DE
Ahn
Jong Seog
JS
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*
D045784:Abietanes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases