Guanxinping ameliorates atherosclerosis via MAPK/NF-κB signaling pathway in ApoE−/− mice

Abstract

Background Atherosclerosis (AS), one of the leading causes of deaths and disabilities, is a kind of vascular disease of lipid disorders and chronic inflammation. Guanxinping (GXP) has been administrated in the treatment of AS for nearly 20 years with satisfying clinical response. This study aimed to explore its underlying mechanisms of anti-atherosclerotic effect in AS. Methods Male ApoE−/− mice were randomized into five groups and fed with either standard diet (control group, CON) or high-fat diet (HFD) for 12 weeks. HFD mice were further divided randomly and either fed continually with HFD as a model group, or atorvastatin (ATO), or low-dose GXP (LGXP), or high-dose GXP (HGXP). After 12 weeks, the body weight, serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were detected. Moreover, serum inflammation cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) concentrations were measured. The structure of aortic tissues was examined by hematoxylin-eosin staining. The mRNA expression of TNF-α, IL-6, and IL-1β were assessed by qPCR. The protein expressions of ICAM-1, VCAM-1, MCP-1, IL-6, IL-1β, p38MAPK, ERK1/2, JNK, IκB-α, and NF-κBp65 in the aorta were also detected. Results GXP treatment reduced serum TG, TC, and LDL-c levels in ApoE−/− mice. Moreover, GXP reduced lipid accumulation in the aorta of ApoE−/− mice, induced by HFD. Furthermore, GXP ameliorated the aorta morphological damage and reduced the serum TNF-α, IL-6, and IL-1β levels. GXP also attenuated the protein expression of ICAM-1, VCAM-1, MCP-1, IL-6, IL-1β, p38MAPK, ERK1/2, JNK, and NF-κBp65, whereas it increased the IκBα level in aortic tissues of ApoE−/− mice. Conclusions Our results show that GXP could ameliorate atherosclerosis, which is mediated by inhibition of the MAPK/NF-κB signaling pathway in ApoE−/− mice. This study provides evidence that GXP might be a promising drug for the treatment of AS.