Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: Involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB

Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Ruscogenin markedly suppressed LPS-induced lung W/D ratio and histopathological changes at oral doses of 0.3–3.0 mg/kg. ► Ruscogenin decreased LPS-induced nitrate/nitrite content, myeloperoxidase activity in the lung tissue at three doses. ► Ruscogenin effectively decreased LPS-induced expression of tissue factor, iNOS and p-p65 in the lung tissue at three doses. ► Ruscogenin significantly reduced plasma nitrate/nitrite content and TF procoagulant activity in LPS-induced ALI mice.