Soyasaponin Ab inhibits lipopolysaccharide-induced acute lung injury in mice

• Soyasaponin Ab attenuated LPS-induced lung pathological changes, NO, TNF-α, IL-6 and IL-1β production.
• Soyasaponin Ab inhibited LPS-induced COX-2 and inducible iNOS expression in lung tissues.
• Soyasaponin Ab up-regulated the activities of SOD and catalase decreased by LPS.
• Soyasaponin Ab inhibited TNF-α, IL-6 and IL-1β production and NF-κB activation in alveolar macrophages.
• Soyasaponin Ab activated LXRα and knockout of LXRα abrogated the anti-inflammatory effects of Soyasaponin Ab.

Soyasaponin Ab (SA) has been reported to have anti-inflammatory effect. However, the effects of SA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) have not been reported. The aim of this study was to investigate the anti-inflammatory effects of SA on LPS-induced ALI and clarify the possible mechanism. The mice were stimulated with LPS to induce ALI. SA was given 1 h after LPS treatment. 12 h later, lung tissues were collected to assess pathological changes and edema. Bronchoalveolar lavage fluid (BALF) was collected to assess inflammatory cytokines and nitric oxide (NO) production. In vitro, mice alveolar macrophages were used to investigate the anti-inflammatory mechanism of SA. Our results showed that SA attenuated LPS-induced lung pathological changes, edema, the expression of cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lung tissues, as well as TNF-α, IL-6, IL-1β, and NO production in mice. Meanwhile, SA up-regulated the activities of superoxide dismutase (SOD) and catalase decreased by LPS in mice. SA also inhibited LPS-induced TNF-α, IL-6 and IL-1β production as well as NF-κB activation in alveolar macrophages. Furthermore, SA could activate Liver X Receptor Alpha (LXRα) and knockdown of LXRα by RNAi abrogated the anti-inflammatory effects of SA. In conclusion, the current study demonstrated that SA exhibited protective effects against LPS-induced acute lung injury and the possible mechanism was involved in activating LXRα, thereby inhibiting LPS-induced inflammatory response.