5,7-dihydroxy-3,4,6-trimethoxyflavone inhibits intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 via the Akt and NF-κB-dependent pathway, leading to suppression of adhesion of monocytes and eosinophils to bronchial epithelial cells.

Abstract

5,7-Dih ydroxy-3′,4′,6′-trimethoxyflavone (eupatilin), the active pharmaco-logical ingredient from Artemisia asiatica Nakai (Asteraceae), is reportedto have a variety of anti-inflammatory properties in intestinal epithelialcells. However, little information is known about the molecular mechanismof eupatilin-induced attenuation of bronchial epithelial inflammation. Thisstudy investigates the role of eupatilin in the adhesion of inflammatorycells such as monocytes and eosinophils to bronchial epithelial cells. Stim-ulation of a human bronchial epithelial cell line (BEAS-2B) with tumournecrosis factor-a (TNF-a) increased the expression of surface adhesionmolecules, including intercellular adhesion molecule 1 (ICAM-1) and vas-cular cell adhesion molecule 1 (VCAM-1), in which eupatilin significantlyinhibited the expression of those adhesion molecules in a dose-dependentmanner. Eupatilin suppressed the TN F- a -induced activation of IjBa andnuclear factor-jB (NF-jB) signals in BEAS-2B cells. The IjB kinase (IKK)activation was also significantly reduced in eupatilin-pre-trea ted BEAS-2Band primary normal human bronchial epithelial (NHB E) cells. However,eupatilin did not influence AP-1 activity in TNF-a-stimulated cells.Suppression of NF-jB signalling induced by eupatilin resulted in the inhi-bition of the exp ression of adhesion molecules and the adhesion of mono-cytes and eosinophils to BEAS-2B cells. Furthermore, eupatilin suppressedthe phosphorylation of Akt in TNF-a-stimulated BEAS-2B and NHBE cells,leading to down-regulation of NF-jB activation and adhesion moleculeexpression and finally to suppression of the inflammatory cell adhesi on toepithelial cells. These results suggest that eupatili n can inhibit the adhesionof inflammatory cells to bronchial epithelial cells via a signalling pathway,including activation of Akt and NF-jB, as well as expression of adhesionmolecules