title: Astragaloside IV inhibits NF- κ B activation and inflammatory gene expression in LPS-treated mice.
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.
authors.affiliation: Linus Pauling Institute and Department of Biochemistry and Biophysics, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, USA.
authors.forename: Wei-Jian
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Linus Pauling Institute and Department of Biochemistry and Biophysics, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, USA.
authors.forename: Balz
authors.initials: B
authors.lastname: Frei
mesh_terms: D000818:Animals; D027885:Astragalus propinquus / Q000737:chemistry*; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D012503:Saponins / Q000737:chemistry*; D015398:Signal Transduction; D014018:Tissue Distribution; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C052064:astragaloside A; D009195:Peroxidase