کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5559246 | 1561564 | 2017 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 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](/preview/png/5559246.png)
- Tanshinones from Salvia miltiorrhiza are potential anti-diabetic candidates.
- Tanshinones 4, 6 and 12 exhibited potent PTP1B inhibitory activity.
- 4 and 6 were mixed-type inhibitors; 12 was a noncompetitive-type inhibitor.
- Tanshinones 4, 6 and 12 exhibited high binding affinity to PTP1B active sites.
- Ring A and furan/dihydrofuran ring D on tanshinones influenced their activity.
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 (â6.4 to â8.7 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.
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Journal: Chemico-Biological Interactions - Volume 278, 25 December 2017, Pages 65-73