Chikusetsusaponin V attenuates lipopolysaccharide-induced acute lung injury in mice by modulation of the NF-κB and LXRα

Abstract

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.