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

Thromb Haemost. 2003 Nov;90(5):904-14. doi: 10.1160/TH03-03-0136.


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-beta-D-xylopyranosyl-6-O-beta-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 TNFalpha-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 TNFalpha-induced specific mRNA levels for E-selectin and VCAM-1. Finally, we could show that AS-IV completely abolished LPS- and TNFalpha-induced nuclear translocation of NF-kappaB and NF-kappaB DNA binding activity in endothelial cells. We conclude that the ability of AS-IV to inhibit the NF-kappaB pathway might be one under-lying mechanism contributing to its anti-inflammatory potential in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / biosynthesis*
  • Cells, Cultured
  • Drugs, Chinese Herbal / pharmacology*
  • E-Selectin / biosynthesis
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Leukocytes / physiology
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Saponins / pharmacology
  • Triterpenes / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Umbilical Veins / cytology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis


  • Anti-Inflammatory Agents
  • Cell Adhesion Molecules
  • Drugs, Chinese Herbal
  • E-Selectin
  • Lipopolysaccharides
  • NF-kappa B
  • Saponins
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • astragaloside A