Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing

Bge is a medicinal plant (Chinese name "Danshen") widely used for the treatment of hyperglycemia in traditional Chinese medicine. Protein tyrosine phosphatase 1B (PTP1B) has been recognized as a potential target for insulin sensitizing for the treatment of diabetes. In this work, PTP1B was...

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Veröffentlicht in:Molecules (Basel, Switzerland) Switzerland), 2022-11, Vol.27 (22), p.7896
Hauptverfasser: Bai, Xiaolin, Fan, Wenqin, Luo, Yingjie, Liu, Yipei, Zhang, Yongmei, Liao, Xun
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Sprache:eng
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Zusammenfassung:Bge is a medicinal plant (Chinese name "Danshen") widely used for the treatment of hyperglycemia in traditional Chinese medicine. Protein tyrosine phosphatase 1B (PTP1B) has been recognized as a potential target for insulin sensitizing for the treatment of diabetes. In this work, PTP1B was displayed at the surface of cells (EC-PTP1B) to be used as a bait for fishing of the enzyme's inhibitors present in the aqueous extract of . Salvianolic acid B, a polyphenolic compound, was fished out by EC-PTP1B, which was found to inhibit PTP1B with an IC value of 23.35 µM. The inhibitory mechanism of salvianolic acid B was further investigated by enzyme kinetic experiments and molecular docking, indicating salvianolic acid B was a non-competitive inhibitor for PTP1B (with Ki and Kis values of 31.71 µM and 20.08 µM, respectively) and its binding energy was -7.89 kcal/mol. It is interesting that in the comparative work using a traditional ligand fishing bait of PTP1B-immobilized magnetic nanoparticles (MNPs-PTP1B), no ligands were extracted at all. This study not only discovered a new PTP1B inhibitor from which is significant to understand the chemical basis for the hypoglycemic activity of this plant, but also indicated the effectiveness of cell display-based ligand fishing in screening of active compounds from complex herbal extracts.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27227896