Tanshinone IIA Protects Endothelial Cells from H₂O₂-Induced Injuries via PXR Activation.
Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome ofSalvia miltiorrhizaBunge (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.
Department of Pharmacology, Anhui Medical University, Hefei 230032, China.|Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Haiyan
H
Zhu
Department of Pharmacology, Anhui Medical University, Hefei 230032, China.
Zhiwu
Z
Chen
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Zengchun
Z
Ma
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Hongling
H
Tan
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Chengrong
C
Xiao
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Xianglin
X
Tang
Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Boli
B
Zhang
Department of Pharmacology, Anhui Medical University, Hefei 230032, China.|Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Yuguang
Y
Wang
Department of Pharmacology, Anhui Medical University, Hefei 230032, China.|Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Yue
Y
Gao
Apoptosis; HUVECs; Inflammation; Oxidative stress; PXR; Tanshinone IIA