Anti-inflammatory effects of Flos Lonicerae Japonicae Water Extract are regulated by the STAT/NF-κB pathway and HO-1 expression in Virus-infected RAW264.7 cells

Int J Med Sci. 2021 Mar 30;18(11):2285-2293. doi: 10.7150/ijms.56198. eCollection 2021.

Abstract

This study examined the effect of the Flos Lonicerae Japonicae water extract (FLJWE), chlorogenic acid, and luteolin on pseudorabies virus (PRV)-induced inflammation in RAW264.7 cells and elucidated related molecular mechanisms. The results revealed that FLJWE and luteolin, but not chlorogenic acid, inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in PRV-infected RAW 264.7 cells. We found that the FLJWE and luteolin suppressed nuclear factor (NF)-κB activation by inhibiting the phosphorylation of signal transducer and activator of transcription 1 and 3 (STAT1 and STAT3, respectively). Moreover, the FLJWE significantly upregulated the expression of pNrf2 and its downstream target gene heme oxygenase-1 (HO-1). Our data indicated that FLJWE and luteolin reduced the expression of proinflammatory mediators and inflammatory cytokines, such as COX-2 and iNOS, through the suppression of the JAK/STAT1/3-dependent NF-κB pathway and the induction of HO-1 expression in PRV-infected RAW264.7 cells. The findings indicate that the FLJWE can be used as a potential antiviral agent.

Keywords: Flos Lonicerae Japonicae water extract (FLJWE); antiviral inflammatory; heme oxygenase-1 (HO-1); pseudorabies virus (PRV).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Disease Models, Animal
  • Flowers / chemistry
  • Heme Oxygenase-1 / metabolism
  • Herpesvirus 1, Suid / immunology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / virology
  • Lonicera / chemistry*
  • Membrane Proteins / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • RAW 264.7 Cells
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Virus Diseases / drug therapy*
  • Virus Diseases / immunology
  • Virus Diseases / virology
  • Water / chemistry

Substances

  • Anti-Inflammatory Agents
  • Antiviral Agents
  • Membrane Proteins
  • NF-kappa B
  • Plant Extracts
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Water
  • Heme Oxygenase-1
  • Hmox1 protein, mouse