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Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing
Salvia miltiorrhiza 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,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693971/ https://www.ncbi.nlm.nih.gov/pubmed/36431993 http://dx.doi.org/10.3390/molecules27227896 |
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author | Bai, Xiaolin Fan, Wenqin Luo, Yingjie Liu, Yipei Zhang, Yongmei Liao, Xun |
author_facet | Bai, Xiaolin Fan, Wenqin Luo, Yingjie Liu, Yipei Zhang, Yongmei Liao, Xun |
author_sort | Bai, Xiaolin |
collection | PubMed |
description | Salvia miltiorrhiza 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 E. coli cells (EC-PTP1B) to be used as a bait for fishing of the enzyme’s inhibitors present in the aqueous extract of S. miltiorrhiza. Salvianolic acid B, a polyphenolic compound, was fished out by EC-PTP1B, which was found to inhibit PTP1B with an IC(50) 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 S. miltiorrhiza 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. |
format | Online Article Text |
id | pubmed-9693971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96939712022-11-26 Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing Bai, Xiaolin Fan, Wenqin Luo, Yingjie Liu, Yipei Zhang, Yongmei Liao, Xun Molecules Article Salvia miltiorrhiza 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 E. coli cells (EC-PTP1B) to be used as a bait for fishing of the enzyme’s inhibitors present in the aqueous extract of S. miltiorrhiza. Salvianolic acid B, a polyphenolic compound, was fished out by EC-PTP1B, which was found to inhibit PTP1B with an IC(50) 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 S. miltiorrhiza 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. MDPI 2022-11-15 /pmc/articles/PMC9693971/ /pubmed/36431993 http://dx.doi.org/10.3390/molecules27227896 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bai, Xiaolin Fan, Wenqin Luo, Yingjie Liu, Yipei Zhang, Yongmei Liao, Xun Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing |
title | Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing |
title_full | Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing |
title_fullStr | Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing |
title_full_unstemmed | Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing |
title_short | Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing |
title_sort | fast screening of protein tyrosine phosphatase 1b inhibitor from salvia miltiorrhiza bge by cell display-based ligand fishing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693971/ https://www.ncbi.nlm.nih.gov/pubmed/36431993 http://dx.doi.org/10.3390/molecules27227896 |
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