Spilanthol Inhibits COX-2 and ICAM-1 Expression via Suppression of NF-B and MAPK Signaling in Interleukin-1-Stimulated Human Lung Epithelial Cells

Spilanthol a phytochemical derived from the Spilanthes acmella plant has antimicrobial, antioxidant, and anti-inflammatory properties. This study evaluated its effects on the expression of intercellular adhesion molecule 1 (ICAM-1) and inflammation-related mediators in IL-1-stimulated human lung epithelial A549 cells. Human lung epithelial A549 cells were pretreated with various concentrations of spilanthol (3-100M) followed by treatment with IL-1 to induce inflammation. The protein levels of pro-inflammatory cytokines, chemokines, and prostaglandin E2 (PGE2) were measured using ELISA. Cyclooxygenase-2 (COX-2), heme oxygenase (HO-1), nuclear transcription factor kappa-B (NF-B), and mitogen-activated protein kinase (MAPK) were measured by immunoblotting. The mRNA expression levels of ICAM-1 and MUC5AC were determined by real-time polymerase chain reaction. Spilanthol decreased the expression of PGE(2), COX-2, TNF-, and MCP-1. It also decreased ICAM-1 expression and suppressed monocyte adhesion to IL-1-stimulated A549 cells. Spilanthol also significantly inhibited the phosphorylation of MAPK and I-B. These results suggest that spilanthol exerts anti-inflammatory effects by inhibiting the expression of the pro-inflammatory cytokines, COX-2, and ICAM-1 by inhibiting the NF-B and MAPK signaling pathways.