Preventive effect of bis-eugenol, a eugenol ortho dimer, on lipopolysaccharide-stimulated nuclear factor kappa B activation and inflammatory cytokine expression in macrophages

Abstract Eugenol exhibits antioxidant and anti-inflammatory activities, but at higher concentrations acts as an oxidant and potent allergen. It was earlier shown that bis -eugenol synthesized by the oxidation of eugenol was less cytotoxic and more highly antioxidative than eugenol. But its anti-inflammatory mechanism remains yet unclear. Since nuclear factor-κB (NF-κB) is a key transcriptional factor in the expression of inflammatory cytokines, we examined whether eugenol and bis -eugenol are inhibitors of NF-κB activation. We observed that bis -eugenol, but not eugenol, clearly inhibited the degradation of inhibitory κB-α in RAW264.7 murine macrophages stimulated with lipopolysaccharide and, consequently, the transcriptional activity of the stimulated NF-κB in the cells. In addition, bis -eugenol actually inhibited LPS-stimulated expression of inflammatory cytokines at both gene and protein levels. These findings suggest that bis -eugenol acts as a potent inhibitor of NF-κB.