Corosolic Acid Ameliorates Atherosclerosis in Apolipoprotein E-Deficient Mice by Regulating the Nuclear Factor-κB Signaling Pathway and Inhibiting Monocyte Chemoattractant Protein-1 Expression

Abstract

Corosolic acid (CRA) is a pentacyclic triterpene acid that has been shown to exhibit an anti-atherosclerotic effect when added to diets of low-density lipoprotein-deficient mice, but the mechanisms are unclear. The purpose of the present study was to investigate the molecular mechanisms by which CRA ameliorates atherosclerosis. The anti-atherosclerosis effect of CRA in apolipoprotein E-deficient mice fed a Western-type diet was evaluated using atherosclerosis lesion area, serum profiles, gene expression and histological lesions. In vitro, the mechanisms responsible for the anti-inflammatory effect of CRA were investigated on a lipopolysaccharide-induced inflammation model. This model was also used to investigate in detail the effects of CRA on gene expression and nuclear factor (NF)-κB activation. Compared with the control group, the CRA-treated group exhibited a significant decrease in atherosclerotic lesion area, as well as expression of monocyte chemoattractant protein-1 (MCP-1) and CCR2. In vitro studies showed that CRA treatment downregulated the mRNA levels of MCP-1, and inhibited monocyte adhesion and migration, together with suppression of NF-κB signaling pathway. CRA is capable of ameliorating atherosclerosis in apolipoprotein E-deficient mice by, partly at least, inhibition of NF-κB activity along with decreased MCP-1 expression.