PTP1B Inhibitory Effect of Abietane Diterpenes Isolated from Salvia miltiorrhiza

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  • Han Yu Mi
    Korea Research Institute of Bioscience and Biotechnology (KRIBB)
  • Oh Hyuncheol
    Korea Research Institute of Bioscience and Biotechnology (KRIBB) College of Natural Science, Silla University
  • Na MinKyun
    Korea Research Institute of Bioscience and Biotechnology (KRIBB)
  • Kim Beom Seok
    Korea Research Institute of Bioscience and Biotechnology (KRIBB)
  • Oh Won Keun
    Korea Research Institute of Bioscience and Biotechnology (KRIBB)
  • Kim Bo Yeon
    Korea Research Institute of Bioscience and Biotechnology (KRIBB)
  • Jeong Dae Gwin
    Korea Research Institute of Bioscience and Biotechnology (KRIBB)
  • Ryu Seong Eon
    Korea Research Institute of Bioscience and Biotechnology (KRIBB)
  • Sok Dai-Eun
    College of Pharmacy, Chungnam National University, Korea
  • Ahn Jong Seog
    Korea Research Institute of Bioscience and Biotechnology (KRIBB)

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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 μM, 22.4±0.6 μM and 56.1±6.3 μM, respectively.

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