title: Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells.
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.
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College, Guizhou 563000, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ran
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau 999078, Macao, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College, Guizhou 563000, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College, Guizhou 563000, China.
authors.forename: Jingshan
authors.initials: J
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau 999078, Macao, China.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen