Schizandrin B attenuates angiotensin II induced endothelial to mesenchymal transition in vascular endothelium by suppressing NF-κB activation

• Published in: Phytomedicine (Stuttgart) 2019-09, Vol.62, p.152955, Article 152955
• Main Authors: You, Shengban, Qian, Jianchang, Wu, Gaojun, Qian, Yuanyuan, Wang, Zhengxian, Chen, Taiwei, Wang, Jingying, Huang, Weijian, Liang, Guang
• Format: Article
• Language: English
• Subjects: Angiotensin II; Angiotensin II - adverse effects; Animals; Anti-Inflammatory Agents - pharmacology; Cells, Cultured; Cyclooctanes - pharmacology; Cytokines - metabolism; Disease Models, Animal; Endothelial cell mesenchymal transition; Endothelium, Vascular - drug effects; Fibrosis - drug therapy; Fibrosis - pathology; Gene Expression Regulation - drug effects; Inflammation - chemically induced; Inflammation - drug therapy; Lignans - pharmacology; Male; Mice; Mice, Inbred C57BL; NF-kappa B p50 Subunit - metabolism; NF-κB; Oxidative Stress - drug effects; Phenotype; Polycyclic Compounds - pharmacology; Schisandrin B; Signal Transduction - drug effects; Vascular remodeling; Vascular Remodeling - drug effects
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2019.152955

Angiotensin II (Ang II)-induced chronic inflammation and oxidative stress often leads to irreversible vascular injury, in which the endothelial to mesenchymal transition (EndMT) in the endothelial layers are involved. Schisandrin B (Sch B), a natural product isolated from traditional Schisandra chinensis, has been reported to exert vascular protective properties with unclear mechanism. This study investigated the protective effects and mechanism of Sch B against Ang II-induced vascular injury. C57BL/6 mice were subcutaneous injected of Ang II for 4 weeks to induce irreversible vascular injury. In vitro, Ang II-induced HUVECs injury was used to study the underlying mechanism. The markers of EndMT, inflammation and oxidative stress were studied both in vitro and in vivo. Pre-administration of Sch B effectively attenuated phenotypes of vascular EndMT and fibrosis in Ang II-treated animals, accompanied with decreased inflammatory cytokine and ROS. The in vitro data from HUVECs suggest that Sch B directly targets NF-κB activation to suppress Ang II-induced EndMT and vascular injury. The activation of EndMT in the presence of Ang II is regulated by the NF-κB, a common player in inflammation and oxidative stress. Ang II-induced inflammation and oxidative stress also contributed to vascular EndMT development and Sch B inhibited inflammation/ROS-mediated EndMT by suppressing NF-κB. EndMT contributes to vascular injury in Ang II-treated mice, and it can be prevented via suppressing NF-κB activation by Sch B treatment. These results also imply that NF-κB might be a promising target to attenuate vascular remodeling induced by inflammation and oxidative stress through an EndMT mechanism. [Display omitted]