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http://dx.doi.org/10.4196/kjpp.2016.20.4.347

Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells  

Ran, Xiaoli (Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College)
Zhao, Wenwen (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau)
Li, Wenping (Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College)
Shi, Jingshan (Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College)
Chen, Xiuping (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.20, no.4, 2016 , pp. 347-355 More about this Journal
Abstract
Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha ($TNF-{\alpha}$) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of $TNF-{\alpha}$ on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe $CM-DCFH_2-DA$. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. $TNF-{\alpha}$ induced LOX-1 expression in a dose- and time- dependent manner in endothelial cells. $TNF-{\alpha}$ induced ROS formation, phosphorylation of $NF-{\kappa}B$ p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. $NF-{\kappa}B$ inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited $TNF-{\alpha}-induced$ LOX-1 expression. CPT and NAC suppressed $TNF-{\alpha}-induced$ LOX-1 expression and phosphorylation of $NF-{\kappa}B$ p65 and ERK in rat aorta. These data suggested that $TNF-{\alpha}$ induced LOX-1 expression via ROS activated $NF-{\kappa}B/ERK$ pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.
Keywords
Cryptotanshinone; Endothelial cells; LOX-1; ROS; $TNF-{\alpha}$;
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