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  • Schisandrin C targets Keap1 and attenuates oxidative stress by activating Nrf2 pathway in Ang II-challenged vascular endothelium.

Schisandrin C targets Keap1 and attenuates oxidative stress by activating Nrf2 pathway in Ang II-challenged vascular endothelium.

Phytotherapy research : PTR (2019-01-12)
Jibo Han, Xiaowen Shi, Yao Du, Fengjie Shi, Bin Zhang, Zhanxiong Zheng, Jianjiang Xu, Liqin Jiang
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Angiotensin II human, ≥93% (HPLC), powder
Sigma-Aldrich
3-Nitro-L-tyrosine, crystalline
Sigma-Aldrich
Schisandrin C, ≥98% (HPLC)

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