Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla chinensis Maxim against H1N1 influenza virus

Inflamm Res. 2018 Feb;67(2):179-189. doi: 10.1007/s00011-017-1109-4. Epub 2017 Nov 24.

Abstract

Objective: The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice.

Methods: The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF. The concentrations of inflammatory cytokines and anti-oxidant factors were detected by ELISA. RT-PCR and western blot assays were used to determine the expression level of TLR pathway's key genes and proteins in lung tissues.

Results: We found that the pathological changes of lung in the viral pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576 mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL-6, TNF-α, IFN-γ, and NO) and down-regulation (IL-2, SOD and GSH) of inflammatory cytokines and anti-oxidant factors were associated with higher clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile, the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-κB p65 of the TLR pathway were reduced by STF treatment.

Conclusions: This study suggested that STF may be a promising candidate for treating H1N1 influenza and subsequent viral pneumonia.

Keywords: Anti-H1N1 influenza; Anti-oxidant factor; Cytokines; Flavonoids; Pneumonia; Toll-like receptors.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • Flavonoids / chemistry
  • Flavonoids / therapeutic use*
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Lamiaceae / chemistry*
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide / biosynthesis
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / pathology
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / pathology
  • Ribavirin / therapeutic use
  • Signal Transduction / drug effects

Substances

  • Antioxidants
  • Cytokines
  • Flavonoids
  • Nitric Oxide
  • Ribavirin