Norkurarinol inhibits Toll-Like Receptor 3 (TLR3)-mediated pro-inflammatory signaling pathway and rotavirus replication

This study examined the effect of norkurarinol on the toll-like receptor 3 (tlr3)- mediated signaling pathways and rotavirus replication. norkurarinol,a lavandulylated flavanone,was isolated from the roots of sophora flavescens,which has been shown to have anti-inflammatory activity. norkurarinol suppressed the nf-κb and ap-1 inducible secreted embryonic alkaline phosphatase (seap) activity induced by poly(i:c),tlr3 ligand,in thp1-blue-cd14 cells with ic 50 values of 20.9 μm. norkurarinol also significantly suppressed the mrna expression of proinflammatory and adhesive molecules induced by poly(i:c) and rotavirus infection. pretreatment of norkurarinol blocked the nf-κb and ap-1 signaling pathway and the phosphorylation of mapks induced by poly(i:c). on the other hand,norkurarinol increased the level of irf3 phosphorylation and ifnβ expression in a dose-dependent manner. moreover,norkurarinol inhibited the rotavirus-induced cytopathic effects. these results suggest that norkurarinol can modulate the tlr3-mediated inflammatory responses and rotavirus replication. © the japanese pharmacological society.