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Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway
INTRODUCTION: Schisandrin B (SchB), the main active constituent in Schisandra chinensis, has antioxidant activities. Endothelial dysfunction leads to various cardiovascular diseases. Oxidative stress is a crucial pathophysiological mechanism underpinning endothelial dysfunction. METHODS: We elucidat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255115/ https://www.ncbi.nlm.nih.gov/pubmed/30538426 http://dx.doi.org/10.2147/DDDT.S184245 |
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author | Han, Jibo Shi, Xiaowen Zheng, Zhanxiong Zhang, Bin Shi, Fengjie Jiang, Liqin Xu, Jianjiang |
author_facet | Han, Jibo Shi, Xiaowen Zheng, Zhanxiong Zhang, Bin Shi, Fengjie Jiang, Liqin Xu, Jianjiang |
author_sort | Han, Jibo |
collection | PubMed |
description | INTRODUCTION: Schisandrin B (SchB), the main active constituent in Schisandra chinensis, has antioxidant activities. Endothelial dysfunction leads to various cardiovascular diseases. Oxidative stress is a crucial pathophysiological mechanism underpinning endothelial dysfunction. METHODS: We elucidated the role and underlying mechanisms of SchB in angiotensin II-induced rat aortic endothelial-cell deficits and explored targets of SchB through siRNA analysis and molecular docking. We measured apoptosis by TUNEL and oxidative stress by dihydroethidium (DHE) and 2’,7’ –dichlorofluorescin diacetate (DCF) staining. RESULTS: Our results demonstrated that SchB significantly ameliorated oxidative stress, mitochondrial membrane-potential depolarization and apoptosis in angiotensin II-challenged rat aortic endothelial cells. We further discovered that these antioxidative effects of SchB were mediated through induction of Nrf2. Importantly, using molecular docking and molecular dynamic simulation, we identified that Keap1, an adaptor for the degradation of Nrf2, was a target of SchB. CONCLUSION: These findings support the potential use of SchB as a Keap1 inhibitor for attenuating oxidative stress, and Keap1 might serve as a therapeutic target in the treatment of cardiovascular diseases. |
format | Online Article Text |
id | pubmed-6255115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62551152018-12-11 Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway Han, Jibo Shi, Xiaowen Zheng, Zhanxiong Zhang, Bin Shi, Fengjie Jiang, Liqin Xu, Jianjiang Drug Des Devel Ther Original Research INTRODUCTION: Schisandrin B (SchB), the main active constituent in Schisandra chinensis, has antioxidant activities. Endothelial dysfunction leads to various cardiovascular diseases. Oxidative stress is a crucial pathophysiological mechanism underpinning endothelial dysfunction. METHODS: We elucidated the role and underlying mechanisms of SchB in angiotensin II-induced rat aortic endothelial-cell deficits and explored targets of SchB through siRNA analysis and molecular docking. We measured apoptosis by TUNEL and oxidative stress by dihydroethidium (DHE) and 2’,7’ –dichlorofluorescin diacetate (DCF) staining. RESULTS: Our results demonstrated that SchB significantly ameliorated oxidative stress, mitochondrial membrane-potential depolarization and apoptosis in angiotensin II-challenged rat aortic endothelial cells. We further discovered that these antioxidative effects of SchB were mediated through induction of Nrf2. Importantly, using molecular docking and molecular dynamic simulation, we identified that Keap1, an adaptor for the degradation of Nrf2, was a target of SchB. CONCLUSION: These findings support the potential use of SchB as a Keap1 inhibitor for attenuating oxidative stress, and Keap1 might serve as a therapeutic target in the treatment of cardiovascular diseases. Dove Medical Press 2018-11-22 /pmc/articles/PMC6255115/ /pubmed/30538426 http://dx.doi.org/10.2147/DDDT.S184245 Text en © 2018 Han et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Han, Jibo Shi, Xiaowen Zheng, Zhanxiong Zhang, Bin Shi, Fengjie Jiang, Liqin Xu, Jianjiang Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway |
title | Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway |
title_full | Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway |
title_fullStr | Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway |
title_full_unstemmed | Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway |
title_short | Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway |
title_sort | schisandrin b protects against angiotensin ii-induced endotheliocyte deficits by targeting keap1 and activating nrf2 pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255115/ https://www.ncbi.nlm.nih.gov/pubmed/30538426 http://dx.doi.org/10.2147/DDDT.S184245 |
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