Feruloylated Oligosaccharides Prevented Influenza-induced Lung
Inflammation via RIG-I/MAVS/TRAF3 Pathway
Abstract
Background and Purpose Uncontrollable inflammation has been the leading
cause of mortality in many acute respiratory infections, including
influenza. In light of the current COVID-19 pandemic, it is vital to
develop valid therapeutics or supplements that are effective in
suppressing lung inflammation. Feruloylated oligosaccharides (FOs) is a
phytochemical constituent that exerts anti-inflammatory activities.
Experimental Approach We established the influenza-induced lung
inflammation model by infecting C57BL/6J mice or MAVS knockout
(Mavstm1Zjc/J) mice with influenza A virus (H1N1). Lung index, histology
analysis, hemagglutination inhibition assay as well as neuraminidase
inhibition assay were performed to evaluate the therapeutic effect of FA
and FOs. PCR, western blot, docking simulation and metabolomics were
done to elucidate the mechanism of FOs anti-inflammatory function in
lung. Key Results Herein, we found that oral administration of FOs
moderately inhibited H1N1 virus infection and reduced lung inflammation
in influenza-infected mice by decreasing a wide spectrum of cytokines in
the lungs. FOs also suppressed transduction of the RIG-I/MAVS/TRAF3
signaling pathway and lowered the expression of NF-κB. Moreover, we
found that the anti-inflammatory function of FOs against influenza
depends on MAVS, which is closely associated with activation of the
downstream signaling cascades and the eventual production of
pro-inflammatory cytokines and type I interferons. Conclusions and
Implications In conclusion, we demonstrated that FOs is an effective
anti-inflammatory agent for treating the lung inflammation caused by
influenza. Such therapeutic effect was likely mediated by
RIG-I/MAVS/TRAF signaling.