Acute lung injury (ALI) is a critical illness syndrome with high morbidity and mortality in patients. Inflammation has been known to be involved in the development of ALI. The purpose of this study was to investigate the effect of puerarin on lipopolysaccharide (LPS)-induced ALI in mice. The pro-inflammatory cytokines TNF-α, IL-6 and IL-1β were determined by ELISA. Western blot analysis was used for detecting the expression of NF-κB, IκBα, and LXRα. And myeloperoxidase (MPO) activity, lung wet/dry (W/D) ratio, and histopathological examination were also detected in lung tissues. The results showed that puerarin significantly inhibited LPS-stimulated MPO activity in lung tissues. Meanwhile, puerarin attenuated lung histopathological changes and lung wet/dry (W/D) ratio. We also found that the expression of pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β were inhibited by puerarin. Puerarin also inhibited LPS-induced TNF-α in RAW264.7 cells and IL-8 in A549 cells. From the results of western blotting, puerarin significantly suppressed LPS-stimulated NF-κB activation. And the expression of LXRα was dose-dependently increased by treatment of puerarin. The inhibition of puerarin on TNF-α production in RAW264.7 cells and IL-8 production in A549 cells were blocked by LXRα inhibitor geranylgeranyl pyrophosphate (GGPP). These results suggested that puerarin attenuated ALI by activating LXRα, which subsequently inhibited LPS-induced inflammatory response.
Keywords: Acute lung injury; LPS; NF-κB; TNF-α.
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