N-salicyloyl tryptamine derivative exerts antiatherosclerotic effects by ameliorating endothelial inflammation and apoptosis.

Abstract

OBJECTIVES: Atherosclerosis (AS) is a chronic inflammatory disease driven by lipids that poses a serious threat to human health. Therefore, the development of drugs with both anti-inflammatory and lipid-lowering properties can provide new hope for the treatment of AS. METHODS: Previous studies have shown that the N-salicyloyl tryptamine derivative B2, formed by combining salicylic acid derivatives and the melatonin skeleton, exhibits strong anti-inflammatory activity and high biosafety. In this study, we used lipopolysaccharide (LPS)/ adenosine triphosphate (ATP) or LPS-stimulated macrophage-conditioned medium to establish an endothelial cell inflammation model. Apolipoprotein E-/- (ApoE-/-) mice fed a high-fat diet (HFD) were used to establish the atherosclerosis animal model. KEY FINDINGS: We found that B2 inhibited LPS/ATP-induced inflammation and apoptosis of endothelial cells, reduced monocyte-endothelial cell adhesion, decreased vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-6 (IL-6), and interleukin-1β, and inhibited the mitogen-activated protein kinase kinase 4/c-Jun N-terminal kinase pathway. In ApoE-/- mice fed a HFD, ELISA and lipid assay revealed that B2 reduced plasma IL-6 and triglyceride levels. Meanwhile, Oil Red O staining and Masson staining showed that B2 decreased the aortic plaque area and the degree of fibrosis. CONCLUSIONS: These findings suggested that B2 exerts both anti-inflammatory and lipid-lowering effects, providing a new intervention approach and direction for the prevention and treatment of AS.