Astragaloside IV inhibits NF- κ B activation and inflammatory gene expression in LPS-treated mice.

Wei-Jian Zhang,Balz Frei

doi:10.1155/2015/274314

Abstract

In this study we investigated the role of astragaloside IV (AS-IV), one of the major active constituents purified from the Chinese medicinal herb Astragalus membranaceus, in LPS-induced acute inflammatory responses in mice in vivo and examined possible underlying mechanisms. Mice were assigned to four groups: vehicle-treated control animals; AS-IV-treated animals (10 mg/kg b.w. AS-IV daily i.p. injection for 6 days); LPS-treated animals; and AS-IV plus LPS-treated animals. We found that AS-IV treatment significantly inhibited LPS-induced increases in serum levels of MCP-1 and TNF by 82% and 49%, respectively. AS-IV also inhibited LPS-induced upregulation of inflammatory gene expression in different organs. Lung mRNA levels of cellular adhesion molecules, MCP-1, TNFα, IL-6, and TLR4 were significantly attenuated, and lung neutrophil infiltration and activation were strongly inhibited, as reflected by decreased myeloperoxidase content, when the mice were pretreated with AS-IV. Similar results were observed in heart, aorta, kidney, and liver. Furthermore, AS-IV significantly suppressed LPS-induced NF-κB and AP-1 DNA-binding activities in lung and heart. In conclusion, our data provide new in vivo evidence that AS-IV effectively inhibits LPS-induced acute inflammatory responses by modulating NF-κB and AP-1 signaling pathways. Our results suggest that AS-IV may be useful for the prevention or treatment of inflammatory diseases.

Highlights

Endothelial cells are a primary target of inflammatory responses, and their injury can lead to vasculopathy and organ dysfunction [1]
We have previously shown that astragaloside IV (AS-IV) inhibits LPSand TNFα-induced adhesion molecule expression and NFκB activation in cultured human endothelial cells [6]
We have previously shown that AS-IV inhibits LPS- and TNFα-induced adhesion molecule expression and consequent adherence of monocytes by modulating NF-κB signaling pathway in cultured human endothelial cells [6]

Summary

Introduction

Endothelial cells are a primary target of inflammatory responses, and their injury can lead to vasculopathy and organ dysfunction [1]. The bacterial endotoxin LPS directly elicits several acute inflammatory responses in endothelial cells, including production of cellular adhesion molecules, such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1), and other proinflammatory mediators, such as TNFα, IL-6, and monocyte chemoattractant protein-1 (MCP-1). Together, these proinflammatory mediators elicit leukocyte adhesion to the vasculature and transmigration into the underlying tissue, causing endothelial injury and dysfunction associated with sepsis [1]. Various agents that block NF-κB signaling have been shown to decrease expression of proinflammatory

Methods

Results

Conclusion