Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
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Norkurarinol Inhibits Toll-Like Receptor 3 (TLR3)-Mediated Pro-inflammatory Signaling Pathway and Rotavirus Replication
Hyun-Mee OhSeung Woong LeeMi Hye ParkMi Hwa KimYoung Bae RyuMyo Sun KimHa-Hyun KimKi Hun ParkWoo Song LeeSu-Jin ParkMun-Chual Rho
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2012 Volume 118 Issue 2 Pages 161-170

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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 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.

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© The Japanese Pharmacological Society 2012
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