title: Norkurarinol inhibits toll-like receptor 3 (TLR3)-mediated pro-inflammatory signaling pathway and rotavirus replication.
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 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.
authors.affiliation: Bioindustrial Process Research Center and AI Control Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Republic of Korea.
authors.forename: Hyun-Mee
authors.initials: HM
authors.lastname: Oh
authors.forename: Seung Woong
authors.initials: SW
authors.lastname: Lee
authors.forename: Mi Hye
authors.initials: MH
authors.lastname: Park
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Kim
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Myo Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Ha-Hyun
authors.initials: HH
authors.lastname: Kim
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Mun-Chual
authors.initials: MC
authors.lastname: Rho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018517:Plant Roots; D012333:RNA, Messenger / Q000378:metabolism; D012401:Rotavirus / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D029909:Sophora / Q000737:chemistry*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D044950:Flavanones; D016328:NF-kappa B; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D018808:Transcription Factor AP-1; C572712:norkurarinol; D020928:Mitogen-Activated Protein Kinases