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 pro-inflammatory 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.