Biomol Ther (Seoul)  
Tanshinone IIA Protects Endothelial Cells from H2O2-Induced Injuries via PXR Activation
Haiyan Zhu1,2, Zhiwu Chen1, Zengchun Ma2, Hongling Tan2, Chengrong Xiao2, Xianglin Tang2, Boli Zhang3, Yuguang Wang1,2,* and Yue Gao1,2,*
1Department of Pharmacology, Anhui Medical University, Hefei 230032, 2Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, 3Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
E-mail: wangyg@bmi.ac.cn (Wang YG), gaoyue@bmi.ac.cn (Gao Y)
Tel: +86-10-68210077-932201 (Wang YG), +86-10-68210077-931312 (Gao Y)
Fax: +86-10-6821-4653 (Wang YG), +86-10-6821-4653 (Gao Y)
Received: August 11, 2016; Revised: October 8, 2016; Accepted: November 3, 2016; Published online: February 6, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established. To study the protective effects of Tan IIA against hydrogen peroxide (H2O2) in human umbilical vein endothelial cells (HUVECs), we pretreated cells with or without different concentrations of Tan IIA for 24 h, then exposed the cells to 400 μM H2O2 for another 3 h. Therefore, our data strongly suggests that Tan IIA may lead to increased regeneration of glutathione (GSH) from the glutathione disulfide (GSSG) produced during the GSH peroxidase-catalyzed decomposition of H2O2 in HUVECs, and the PXR plays a significant role in this process. Tan IIA may also exert protective effects against H2O2-induced apoptosis through the mitochondrial apoptosis pathway associated with the participation of PXR. Tan IIA protected HUVECs from inflammatory mediators triggered by H2O2 via PXR activation. In conclusion, Tan IIA protected HUVECs against H2O2-induced cell injury through PXR-dependent mechanisms.
Keywords: Tanshinone IIA, PXR, HUVECs, Oxidative stress, Apoptosis, Inflammation


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