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 IκB-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.
ASJC Scopus subject areas
- Pharmaceutical Science