Cargando…
A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan
Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change a...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273035/ https://www.ncbi.nlm.nih.gov/pubmed/27735870 http://dx.doi.org/10.3390/molecules21101340 |
_version_ | 1783377291631394816 |
---|---|
author | Liu, Ningning Li, Lailai Zhu, Xin Ling, Zhiqiang Feng, Jianguo Hu, Ying Wang, Yi Mou, Lijun Wang, Yi |
author_facet | Liu, Ningning Li, Lailai Zhu, Xin Ling, Zhiqiang Feng, Jianguo Hu, Ying Wang, Yi Mou, Lijun Wang, Yi |
author_sort | Liu, Ningning |
collection | PubMed |
description | Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images. With the aid of chromatographic separation and mass spectrometry, we achieved the rapid and reliable screening of active compounds from the Chinese herbal medicine Tong-Mai-Yang-Xin-Wan (TMYX) for treating EMT. Five fractions were found to exert anti-EMT activity and were further identified by liquid chromatography coupled with tandem mass spectrometry. Glycyrrhizic acid, glyasperin A, and licorisoflavan A were found to inhibit EMT. The proposed approach was successfully applied to screen active compounds from TMYX on TGF-β1-stimulated HK-2 cells and may offer a new means for identifying lead compounds for treating EMT from registered Chinese herbal medicines. |
format | Online Article Text |
id | pubmed-6273035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62730352018-12-28 A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan Liu, Ningning Li, Lailai Zhu, Xin Ling, Zhiqiang Feng, Jianguo Hu, Ying Wang, Yi Mou, Lijun Wang, Yi Molecules Article Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images. With the aid of chromatographic separation and mass spectrometry, we achieved the rapid and reliable screening of active compounds from the Chinese herbal medicine Tong-Mai-Yang-Xin-Wan (TMYX) for treating EMT. Five fractions were found to exert anti-EMT activity and were further identified by liquid chromatography coupled with tandem mass spectrometry. Glycyrrhizic acid, glyasperin A, and licorisoflavan A were found to inhibit EMT. The proposed approach was successfully applied to screen active compounds from TMYX on TGF-β1-stimulated HK-2 cells and may offer a new means for identifying lead compounds for treating EMT from registered Chinese herbal medicines. MDPI 2016-10-10 /pmc/articles/PMC6273035/ /pubmed/27735870 http://dx.doi.org/10.3390/molecules21101340 Text en © 2016 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Ningning Li, Lailai Zhu, Xin Ling, Zhiqiang Feng, Jianguo Hu, Ying Wang, Yi Mou, Lijun Wang, Yi A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan |
title | A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan |
title_full | A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan |
title_fullStr | A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan |
title_full_unstemmed | A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan |
title_short | A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan |
title_sort | high content screening assay to identify compounds with anti-epithelial-mesenchymal transition effects from the chinese herbal medicine tong-mai-yang-xin-wan |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273035/ https://www.ncbi.nlm.nih.gov/pubmed/27735870 http://dx.doi.org/10.3390/molecules21101340 |
work_keys_str_mv | AT liuningning ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT lilailai ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT zhuxin ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT lingzhiqiang ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT fengjianguo ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT huying ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT wangyi ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT moulijun ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT wangyi ahighcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT liuningning highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT lilailai highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT zhuxin highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT lingzhiqiang highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT fengjianguo highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT huying highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT wangyi highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT moulijun highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan AT wangyi highcontentscreeningassaytoidentifycompoundswithantiepithelialmesenchymaltransitioneffectsfromthechineseherbalmedicinetongmaiyangxinwan |