Acetylshikonin Suppresses Atherogenesis By Attenuating Vascular Inflammation In Apolipoprotein E-Deficient Mice

Atherosclerosis is a chronic inflammatory disease and underlies cause of death worldwide. Acetylshikonin (AS), as the main ingredient of Zicao, is proposed to have capacity to suppress inflammation. However, the effects and related mechanisms of AS on atherosclerosis are unclear. 8-week-old apolipoprotein E deficient (apoE(-/-)) mice were received 12-week high fat diet (HFD), and were randomly given either AS (100 mg/kg body weight, once daily) or vehicle i.p. for 4 weeks. Compared with HFD-fed apoE(-/-) mice, administration of AS resulted not only in suppressed body weight gain, but also in decreased triglyceride (TC) level. However, there was no effect on total cholesterol (TC), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL) levels. Further investigation of lipid accumulation using oil red O staining showed that the atherosclerotic lesions were significantly decreased in aortic sinus and arch after AS treatment. Moreover, immunohistochemistry staining exhibited that the infiltration of inflammatory cells (e.g. T-lymphocytes, neutrophils and macrophages) in plaque was markedly attenuated by AS administration. AS-treated mice displayed reduced intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aorta, concomitantly with decreased serum interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) levels. In addition, AS treatment suppressed nuclear factor kappa B (NF-kappa B) activation in aorta of HFD-fed apoE(-/-) mice, indicated by attenuated p65 and p50 nuclear translocation. Taken together, these results demonstrate that AS ameliorates vascular inflammation and atherogenesis at least partially via inhibiting NF-kappa B signaling. Our findings suggest that AS may be a useful therapeutic agent for the treatment of atherosclerosis.