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

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-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-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.