Journal of Pharmacological Sciences (Jan 2012)

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

  • Hyun-Mee Oh,
  • Seung Woong Lee,
  • Mi Hye Park,
  • Mi Hwa Kim,
  • Young Bae Ryu,
  • Myo Sun Kim,
  • Ha-Hyun Kim,
  • Ki Hun Park,
  • Woo Song Lee,
  • Su-Jin Park,
  • Mun-Chual Rho

DOI
https://doi.org/10.1254/jphs.11077fp
Journal volume & issue
Vol. 118, no. 2
pp. 161 – 170

Abstract

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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