Chikusetsusaponin V attenuates lipopolysaccharide-induced acute lung injury in mice by modulation of the NF-κB and LXRα
International Immunopharmacology(2019)
摘要
Acute lung injury (ALI) is an excessive and uncontrolled inflammatory response in lung, of which remains the leading cause of morbidity and mortality in worldwide. Chikusetsusaponin V (CsV), a bioactive compounds derived from Panacis Japonica, has been reported to have anti-inflammatory effects. However, it is still unclear whether CsV can protect mice against ALI. This study aimed to investigate the protective roles and potential mechanisms of CsV on lipopolysaccharide (LPS)-induced ALI in mice. The mice were pretreated with CsV (5, 10, and 20 mg/kg) four days before LPS treatment. 24 h later LPS administration, the histopathological changes, wet/dry ratio, and MPO activity in lung tissues were detected. The inflammatory cells, including total cells, neutrophils, and macrophages in the bronchoalveolar lavage fluid (BALF) were detected under a light microscope. The levels of pro-inflammatory cytokine TNF-α, IL-1β, and IL-6 in the BALF were assessed by ELISA. In addition, the expressions of NF-κB and LXRα in lung tissues were detected by western blot analysis. The results showed that pretreatment of CsV attenuated the lung histopathological damages, lung wet/dry ratio, and MPO activity induced by LPS. In addition, CsV also reduced the LPS-induced increases in the number of inflammatory cells and pro-inflammatory cytokine TNF-α, IL-1β, and IL-6 in the BALF. Furthermore, western blot analysis showed that CsV significantly inhibited the activation of NF-κB signaling pathway. CsV dose-dependently increased the expression of LXRα. In vitro, the anti-inflammatory effects of CsV can be reversed by LXRα inhibitor, GGPP. In conclusion, the results showed that CsV protected against LPS-induced ALI due to its ability to activate LXRα.
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关键词
LPS,Lung injury,Chikusetsusaponin V,LXRα
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