Tectorigenin Reduces Dabie bandavirus-Induced Cytokine Storm by Regulating Toll-Like Receptor 7/Extracellular Signal-Regulated Kinase Pathway

Chem Biol Drug Des. 2024 Dec;104(6):e70005. doi: 10.1111/cbdd.70005.

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging infectious disease caused by Dabie bandavirus (DBV). Tectorigenin has been demonstrated to exert anti-inflammatory effect. Here, we aimed to investigate the effects of tectorigenin on DBV-induced cytokine storm. Effects of tectorigenin on cytokines in DBV-infected THP-1 cells and plasma samples of Type I interferon receptor (IFNAR)-/- mice infected with DBV were detected. The changes in body weight and survival time of mice were recorded. The liver, spleen, kidney, and lymph node tissues were collected for hematoxylin-eosin staining. We demonstrated that tectorigenin reduced the expression levels of inflammatory cytokines in both DBV-infected THP-1 cells and plasma samples of IFNAR-/- mice infected with DBV. Tectorigenin attenuated DBV-induced histopathological changes in mice. Mechanistically, tectorigenin attenuated DBV-induced phosphorylation of inhibitor of kappa-B kinase alpha/beta (IKKα/β) of the nuclear factor-κB (NF-κB) signaling pathway, extracellular signal-regulated kinase (ERK) of the mitogen-activated protein kinase (MAPK) signaling pathway and might function by downregulation of Toll-like receptor. The result of this study suggested that tectorigenin exerted anti-inflammatory effects in vivo and in vitro and could serve as a novel potential therapeutic strategy for SFTS.

Keywords: extracellular signal–regulated kinase (ERK); inflammation; severe fever with thrombocytopenia syndrome; tectorigenin; toll‐like receptor 7 (TLR‐7).

MeSH terms

  • Animals
  • Cytokine Release Syndrome / drug therapy
  • Cytokines / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Isoflavones* / chemistry
  • Isoflavones* / pharmacology
  • Isoflavones* / therapeutic use
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • Signal Transduction / drug effects
  • THP-1 Cells

Substances

  • Isoflavones
  • tectorigenin
  • Extracellular Signal-Regulated MAP Kinases
  • NF-kappa B
  • Cytokines
  • Receptor, Interferon alpha-beta