Melittin inhibits atherosclerosis in LPS/high-fat treated mice through atheroprotective actions

Abstract

Aim: Atherosclerosis is influenced by multiple environmental factors that involve a complex interaction between blood components and the arterial wall and is characterized by inflammatory reactions. Melittin has been used in treatment of various chronic inflammatory diseases. We investigated the effects of melittin regulated atherosclerotic changes in an animal model of atherosclerosis. Methods: Atherosclerotic mice were induced by intraperitoneal (i.p) injection of lipopolysaccharide (LPS, 2 mg/kg) three times a week and an atherogenic diet for 12 weeks. Results: Melittin (0.1 mg/kg) treatment was administered with i.p injection. Melittin treatment showed that total cholesterol and triglyceride levels decreased in atherosclerotic mice however, high-density lipoprotein cholesterol (HDL-C) levels were higher in atherosclerotic mice treated with melittin than in atherosclerotic mice. H&E staining showed that heart and descending aorta were significantly recovered by melittin, compared to atherosclerotic mice. In addition, melittin decreased the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1 β, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, fibronectin and transforming growth factor (TGF)-β1 in atherosclerotic mice. In vitro, melittin decreased LPS-induced THP-1 cells-derived macrophages TNF-α and IL-1β expression levels and nuclear factor (NF)-κB signal pathway. Conclusions: These results demonstrate that melittin has an anti-atherogenic effect by suppression of pro-inflammatory cytokines and adhesion molecules.