Astragaloside IV Inhibits NF-κB Activation and Inflammatory Gene Expression in LPS-Treated Mice

Abstract EN

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.