Alleviation of severe inflammatory responses in LPS-exposed mice by Schisantherin A

In this study, we aimed to investigate our hypothesis starting that Schisantherin A (SchA), which exerts significant anti-inflammatory effects in vitro, could reduce the pulmonary inflammatory response in an acute lung injury (ALI) model. ALI was induced in mice by exposure to lipopolysaccharide (LPS, 20 mg/kg), and the inflammatory mediator production, neutrophil infiltration, and histopathological changes were evaluated. SchA at a dose of 100 mg/kg significantly improved survival rate of mice injected with LPS. The levels of TNF-alpha and IL-6 in bronchoalveolar lavage fluid (BALF) and the histopathological changes due to the injury were significantly inhibited when SchA was administered before or after LPS insult, and the infiltration of neutrophils and macrophages in lung tissues induced by LPS were suppressed by SchA. Additionally, pretreatment with SchA notably blocked the activation of nuclear factor-kappaB (NF-kappa B) and mitogen-activated protein kinases (MAPKs). Taken together, SchA showed obvious anti-inflammatory effects in an LPS-induced ALI model via blockage of the NF-kappa B and MAPK pathways. Thus, SchA may be an innovative therapy for inflammatory diseases. (C) 2014 Elsevier B.V. All rights reserved.