Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB activation and adhesion molecule expression.
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.
Zhang
Wei-Jian
WJ
Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria.
Hufnagl
Peter
P
Binder
Bernd R
BR
Wojta
Johann
J
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007962:Leukocytes / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D004365:Drugs, Chinese Herbal; D019040:E-Selectin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C052064:astragaloside A