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Thromb Haemost 2003; 90(05): 904-914
DOI: 10.1160/TH03-03-0136
Wound Healing and Inflammation/Infection
Schattauer GmbH

Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-κB activation and adhesion molecule expression

Wei-Jian Zhang
1   Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria
2   Current address: Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA
,
Peter Hufnagl
1   Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria
,
Bernd R. Binder
1   Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria
,
Johann Wojta
1   Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria
› Author AffiliationsFinancial support: During this study WJZ was supported by a North-South Dialogue scholarship EH-project 894 from The Austrian Academic Exchange Service (öAD). This work was supported by grants from The Austrian Fund for the Promotion of Scientific Research to JW (P9479) and BRB (P8011 and P8854).
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Publication History

Received 07 March 2003

Accepted after resubmission 03 July 2003

Publication Date:
05 December 2017 (online)

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Summary

The regulated expression of adhesion molecules on the surface of endothelial cells is a key process in the pathogenesis of inflammation. The saponin astragaloside IV (AS-IV), a 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosylcycloastragenol purified from the Chinese medical herb Astragalus membranaceus(Fisch) Bge.has been shown to have anti-inflammatory effects in vivo.In this study we have investigated the effect of AS-IV on cytokine-and LPS-stimulated expression of adhesion molecules in and leukocyte adhesion to endothelial cells. We have demonstrated that AS-IV significantly reduced the adhesion promoting activity of LPS-stimulated HUVECs for polymorph-nuclear leukocytes (PMNs) and the monocytic cell line THP-1. Furthermore, by using specific cell ELISAs we could show that AS-IV decreased the LPS-induced expression of E-selectin and VCAM-1 on the surface of HUVECs in a dose and time dependent manner, whereas the expression of ICAM-1 was not affected by AS-IV. AS-IV also inhibits TNFβ-induced VCAM-1 expression. The saponin octyl-D-glucopyranoside had no effect on the LPS-induced expression of E-selectin and VCAM-1 excluding an unspecific detergent-like effect of AS-IV. Moreover, AS-IV significantly inhibited LPS- and TNFβ-induced specific mRNA levels for E-selectin and VCAM-1. Finally, we could show that AS-IV completely abolished LPS- and TNFα-induced nuclear translocation of NF-κB and NF-κB DNA binding activity in endothelial cells. We conclude that the ability of AS-IV to inhibit the NF-κB pathway might be one underlying mechanism contributing to its anti-inflammatory potential in vivo.

Keywords

Endothelial cells - adhesion molecules - lipopolysaccharide - cyto-kines - inflammation
 

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