Suppression of lung inflammation by the methanol extract of <i>Spilanthes acmella</i> Murray is related to differential regulation of NF-κB and Nrf2

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P>Although <I>Spilanthes acmella</I> has been used to relieve inflammation, fever, pain, or infection in traditional Asian medicine, experimental evidence supporting these functions is scarce. Here, we examined an anti-inflammatory function and a possible underlying mechanism of <I>S. acmella</I> Murray (SAM).</P> <P><B>Materials and method</B></P> <P>The methanol extract of SAM was fingerprinted by HPLC. C57BL/6 mice were administered with a single intratracheal (i.t.) LPS and 2 h later with a single i.t. SAM. The effect of SAM on lung inflammation was assessed by histology, semi-quantitative RT-PCR, and MPO assay of lung tissue. The effects of SAM on a pro-inflammatory factor NF-κB and an anti-inflammatory factor Nrf2 were analyzed by immunoblotting of nuclear proteins and by semi-quantitative RT-PCR analysis of mRNA of the genes governed by these transcription factors. V5-Nrf2 was precipitated by an anti-V5 antibody and the ubiquitinated V5-Nrf2 was revealed by immunoblotting of HA-tagged ubiquitin.</P> <P><B>Results</B></P> <P>The i.t. SAM robustly diminished a neutrophilic lung inflammation induced by i.t. LPS treatment of mice. In RAW 264.7 cells, SAM suppressed the nuclear localization of NF-κB and the expression of NF-κB-dependent cytokine genes. SAM increased the level of Nrf2 in the nucleus and the expression of Nrf2-dependent genes while suppressing ubiquitination of Nrf2.</P> <P><B>Conclusion</B></P> <P>Our results suggest that SAM can suppress a neutrophilic inflammation in mouse lungs, which is associated with suppressed NF-κB and activated Nrf2. Our results provide experimental evidence supporting the anti-inflammatory function of <I>S. acmella</I>.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>