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Schisandrin B protects against angiotensin II-induced endotheliocyte deficits by targeting Keap1 and activating Nrf2 pathway

Authors Han J, Shi X, Zheng Z, Zhang B, Shi F, Jiang L, Xu J

Received 16 August 2018

Accepted for publication 26 October 2018

Published 22 November 2018 Volume 2018:12 Pages 3985—3997

DOI https://doi.org/10.2147/DDDT.S184245

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Georgios D. Panos


Jibo Han,* Xiaowen Shi,* Zhanxiong Zheng, Bin Zhang, Fengjie Shi, Liqin Jiang, Jianjiang Xu

Department of Cardiology, Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, China

*These authors contributed equally to this work

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.

Keywords: schisandrin B, Keap1, oxidative stress, angiotensin II, rat aortic endothelial cell

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