Astragalus polysaccharide from Astragalus Melittin ameliorates inflammation via suppressing the activation of TLR-4/NF-κB p65 signal pathway and protects mice from CVB3-induced virus myocarditis

Abstract

Inflammation plays a crucial role in regulating cardiomyopathy and injuries of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). It has been reported that Astragalus polysaccharide (AP) from Astragalus Melittin could inhabit inflammatory gene expression under a variety of pathological conditions. However, the functional roles of AP in CVB3-induced VM still remain unknown. Here, we found that AP significantly enhanced survival for CVB3-induced mice. AP protected the mice against CVB3-induced myocardial injuries characterized by the increased body weight and depressed serum level of creatine kinase-MB (CK-MB), aspartate transaminases (AST) and lactate dehydrogenase (LDH), enhanced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). At the pathological level, AP ameliorated the mice against CVB3-induced myocardial damage, dilated cardiomyopathy and chronic myocardial fibrosis. We subsequently found that AP significantly suppressed CVB3-induced expression of inflammation marker (IL-1β, IL-6, TNF-α, INF-γ and MCP-1) in heart. Furthermore, we confirmed that AP suppressed the CVB3-induced expression of TLR-4 and phosphorylated NF-κB p65 in heart. Taken together, the data suggest that AP protects against CVB3-induced myocardial damage and inflammation, which may partly attribute to the regulation of TLR-4/NF-κB p65 signal pathway, moreover, suppressive effect of AP on CVB3-induced activation of TLR-4/NF-κB p65 signal was TNF-α-independent.

Keywords: Astragalus polysaccharide from Astragalus Melittin; Inflammation; TLR-4/NF-κB p65 signal pathway; Virus myocarditis.