Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Tanshinone IIA Protects Endothelial Cells from H2O2-Induced Injuries via PXR Activation

  • Zhu, Haiyan (Department of Pharmacology, Anhui Medical University) ;
  • Chen, Zhiwu (Department of Pharmacology, Anhui Medical University) ;
  • Ma, Zengchun (Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine) ;
  • Tan, Hongling (Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine) ;
  • Xiao, Chengrong (Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine) ;
  • Tang, Xianglin (Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine) ;
  • Zhang, Boli (Tianjin University of Traditional Chinese Medicine) ;
  • Wang, Yuguang (Department of Pharmacology, Anhui Medical University) ;
  • Gao, Yue (Department of Pharmacology, Anhui Medical University)
  • Received : 2016.08.11
  • Accepted : 2016.11.03
  • Published : 2017.11.01
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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 ($H_2O_2$) 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 $400{\mu}M$ $H_2O_2$ 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 $H_2O_2$ in HUVECs, and the PXR plays a significant role in this process. Tan IIA may also exert protective effects against $H_2O_2$-induced apoptosis through the mitochondrial apoptosis pathway associated with the participation of PXR. Tan IIA protected HUVECs from inflammatory mediators triggered by $H_2O_2$ via PXR activation. In conclusion, Tan IIA protected HUVECs against $H_2O_2$-induced cell injury through PXR-dependent mechanisms.

Keywords

References

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