C. H. Lin, C. W. Chang, C. C. Wang
Sep 1, 2002
Citations
0
Influential Citations
26
Citations
Quality indicators
Journal
Journal of Pharmacy and Pharmacology
Abstract
We examined the inhibitory mechanism of byakangelicol, isolated from Angelica dahurica, on interleukin‐1β (IL‐1β)‐induced cyclooxygenase‐2 (COX‐2) expression and prostaglandin E2 (PGE2) release in human pulmonary epithelial cell line (A549). Byakangelicol (10–50 μm) concentration‐dependently attenuated IL‐1β‐induced COX‐2 expression and PGE2 release. The selective COX‐2 inhibitor, NS‐398 (0.01–1 μm), and byakangelicol (10–50 μm) both concentration‐dependently inhibited the activity of the COX‐2 enzyme. Byakangelicol, at a concentration up to 200 μm, did not affect the activity and expression of COX‐1 enzyme. IL‐1β‐induced p44/42 mitogen‐activated protein kinase (MAPK) activation was inhibited by the MAPK/extracellular signal‐regulated protein kinase (MEK) inhibitor, PD 98059 (30 μm), while byakangelicol (50 μm) had no effect. Treatment of cells with byakangelicol (50 μm) or pyrrolidine dithiocarbamate (PDTC; 50 μm) partially inhibited IL‐1β‐induced degradation of 1κB‐α in the cytosol, translocation of p65 NF‐κB from the cytosol to the nucleus and the NF‐κB‐specific DNA‐protein complex formation. Taken together, we have demonstrated that byakangelicol inhibits IL‐1β‐induced PGE2 release in A549 cells; this inhibition may be mediated by suppression of COX‐2 expression and the activity of COX‐2 enzyme. The inhibitory mechanism of byakangelicol on IL‐1β‐induced COX‐2 expression may be, at least in part, through suppression of NF‐κB activity. Therefore, byakangelicol may have therapeutic potential as an anti‐inflammatory drug on airway inflammation.