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. 2019 Jun 11;118(2):161–170. doi: 10.1254/jphs.11077FP

Norkurarinol Inhibits Toll-Like Receptor 3 (TLR3)-Mediated Pro-inflammatory Signaling Pathway and Rotavirus Replication

Hyun-Mee Oh 1,†, Seung Woong Lee 1,†, Mi Hye Park 1, Mi Hwa Kim 1, Young Bae Ryu 2, Myo Sun Kim 1, Ha-Hyun Kim 2, Ki Hun Park 3, Woo Song Lee 2, Su-Jin Park 2,*a, Mun-Chual Rho 1,*b
PMCID: PMC7128696  PMID: 22293288

Abstract

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 IC50 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.

Keywords: norkurarinol, toll-like receptor 3 (TLR3), inflammatory response, rotavirus, dsRNA

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