Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells.
10.4196/kjpp.2016.20.4.347
- Author:
Xiaoli RAN
1
;
Wenwen ZHAO
;
Wenping LI
;
Jingshan SHI
;
Xiuping CHEN
Author Information
1. Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College, Guizhou 563000, China. shijs@zmc.edu.cn
- Publication Type:Original Article
- MeSH:
Animals;
Aorta;
Blotting, Western;
Endothelial Cells*;
Fluorescence;
Human Umbilical Vein Endothelial Cells;
Lipoproteins;
Medicine, Chinese Traditional;
Phosphorylation;
Rats;
Reactive Oxygen Species*;
Real-Time Polymerase Chain Reaction;
RNA, Messenger;
Rotenone;
Salvia miltiorrhiza;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2016;20(4):347-355
- CountryRepublic of Korea
- Language:English
-
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-α) 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-α 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-DCFH2-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-α induced LOX-1 expression in a dose- and time-dependent manner in endothelial cells. TNF-α induced ROS formation, phosphorylation of NF-κB p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. NF-κB inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited TNF-α-induced LOX-1 expression. CPT and NAC suppressed TNF-α-induced LOX-1 expression and phosphorylation of NF-κB p65 and ERK in rat aorta. These data suggested that TNF-α induced LOX-1 expression via ROS activated NF-κB/ERK pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.
