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Schisandrin C targets Keap1 and attenuates oxidative stress by activating Nrf2 pathway in Ang II‐challenged vascular endothelium
Author(s) -
Han Jibo,
Shi Xiaowen,
Du Yao,
Shi Fengjie,
Zhang Bin,
Zheng Zhanxiong,
Xu Jianjiang,
Jiang Liqin
Publication year - 2019
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6271
Subject(s) - oxidative stress , endothelial dysfunction , schisandra chinensis , pharmacology , keap1 , endothelium , angiotensin ii , regulator , vascular smooth muscle , medicine , chemistry , endocrinology , biochemistry , receptor , transcription factor , pathology , traditional chinese medicine , alternative medicine , smooth muscle , gene
Vascular endothelial dysfunction plays a crucial role in the pathogenesis of cardiovascular diseases. Oxidative stress is a key pathophysiological mechanism underpinning endothelial dysfunction. Schisandrin C (Sch C), a dibenzocyclooctadiene derivative of Schisandra chinensis , has antioxidative properties. Here, we report the use of Sch C as a novel therapeutic for the treatment of angiotensin II (Ang II)‐induced endothelial deficits and explore the underlying mechanisms and the target of Sch C. Our results demonstrated that Sch C treatment prevents aorta oxidative stress and improves relaxation in mice, challenged with subcutaneous infusion of Ang II. In addition, Sch C significantly ameliorates Ang II‐induced oxidative stress in rat aortic endothelial cells. We then discovered that these antioxidative effects of Sch C are mediated through the induction of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2). Using an expression plasmid and molecular docking, we identified that Kelch‐like ECH‐associated protein‐1 (Keap1), a negative regulator of Nrf2, is a target of Sch C. These findings provide evidence for the potential use of Sch C as an antioxidative agent for treatment of vascular endothelial deficits.