2. Academic Validation
  3. Characterization of the inhibitory activity of natural tanshinones from Salvia miltiorrhiza roots on protein tyrosine phosphatase 1B

Characterization of the inhibitory activity of natural tanshinones from Salvia miltiorrhiza roots on protein tyrosine phosphatase 1B

  • Chem Biol Interact. 2017 Dec 25;278:65-73. doi: 10.1016/j.cbi.2017.10.013.
Da Hye Kim 1,  Pradeep Paudel 1,  Ting Yu 1,  Thi Men Ngo 2,  Jeong Ah Kim 2,  Hyun Ah Jung 3,  Takako Yokozawa 4,  Jae Sue Choi 5
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Science, Pukyong National University, Busan 48513, Republic of Korea.
  • 2 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
  • 3 Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Republic of Korea. Electronic address: [email protected].
  • 4 Graduate School Science and Engineering for Research, University of Toyama, Toyama 930-8555, Japan.
  • 5 Department of Nutrition and Food Science, Pukyong National University, Busan 48513, Republic of Korea. Electronic address: [email protected].
PMID: 29031618 DOI: 10.1016/j.cbi.2017.10.013
Abstract

Protein tyrosine Phosphatase 1B (PTP1B) is a negative regulator that plays an important role in many signaling pathways, especially those associated with Insulin resistance. In this study, we investigated the anti-diabetic potential of 12 natural tanshinones isolated from Salvia miltiorrhiza (S. miltiorrhiza) Bunge (Lamiaceae), deoxyneocryptotanshinone (1), grandifolia F (2), ferruginol (3), cryptotanshinone (4), tanshinone IIA (5), tanshinol B (6), tanshinone IIB (7), tanshinonal (8), methyl tanshinonate (9), 15,16-dihydrotanshinone I (10), tanshinone I (11), and dehydrodanshenol A (12) and evaluated their inhibitory activity against PTP1B. Tanshinones 4, 6 and 12 exhibited potent PTP1B inhibitory activity with IC50 values of 5.5 ± 0.9, 4.7 ± 0.4 and 8.5 ± 0.5 μM, respectively. In addition, tanshinones 1-3, 5 and 7-11 showed promising dose-dependent inhibition of PTP1B over IC50 values ranging from 18.6 to 254.8 μM. Enzyme kinetic analysis of PTP1B inhibition revealed that 4 and 6 were mixed -noncompetitive type inhibitors, whereas 12 was a classical-noncompetitive type inhibitor. Furthermore, 4, 6 and 12 were docked with the PTP1B Enzyme using molecular docking simulations (AutoDock 4.2) and exhibited negative binding energy (-6.4 to -8.7 kcal/mol), indicating high binding affinity to PTP1B active site residues. Structure-activity relationships (SAR) analysis revealed that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influenced their activity. Overall, results indicated that tanshinones from S. miltiorrhiza are potential anti-diabetic candidates that should be explored in the development of preventive and therapeutic modalities for the treatment of diabetes as well as diabetes-associated complications.

Keywords

Anti-diabetes; Lamiaceae; Molecular docking; PTP1B; Salvia miltiorrhiza; Tanshinone.

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