Protective effect of genkwanin against lipopolysaccharide-induced acute lung injury in mice with p38 mitogen-activated protein kinase and nuclear factor-κB pathway inhibition

Abstract

• Genkwanin inhibited the lung histopathological changes in LPS-induced ALI mice. • Genkwanin inhibited lung oedema, alveolar–capillary barrier, and leukocytes infiltration dysfunction in LPS-induced ALI mice. • Genkwanin reduced the secretion of IL-1β, IL-6, and TNF-α in LPS-induced ALI mice. • Genkwanin reduced IκB degradation and p65 phosphorylation in LPS-induced ALI mice. • Genkwanin reduced p38 MAPK phosphorylation in LPS-induced ALI mice. Acute lung injury (ALI) is a life-threatening clinical syndrome. Genkwanin is a nonglycosylated flavonoid that has several biopharmacological effects, such as anti-inflammatory, antioxidative, and immunomodulator effects. This study investigated the protective effect and mechanism of genkwanin in a lipopolysaccharide (LPS)-induced mouse model. Histopathological analysis indicated that genkwanin had a potential ameliorative effect on LPS-induced ALI. Genkwanin also inhibited several pathogenic features induced by LPS, including lung oedema, alveolar-capillary barrier dysfunction, and leukocyte and neutrophil infiltration. In addition, it inhibited NF-κB pathway activation, including phosphorylation of p65 and degradation of IκB, induced by LPS. Genkwanin also inhibited the phosphorylation of the p38 MAPK pathway induced by LPS, although it did not inhibit the phosphorylation of extracellular signal-regulated kinases or c-Jun N -terminal kinases induced by LPS. In conclusion, our results indicate that genkwanin has a protective effect against LPS-induced ALI that it exerts by inhibiting NF-κB pathway activation and p38 MAPK phosphorylation.