Glabridin attenuates lipopolysaccharide-induced acute lung injury by inhibiting p38MAPK/ERK signaling pathway.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a complication caused by pulmonary and/or external factors. In this study, we investigated the protective mechanisms of glabridin in lipopolysaccharide (LPS) induced ARDS in rats.

RESULTS: GLA treatment at dose of 30 mg/kg decreased LPS-induced lung W/D ratio and alleviated evident lung histopathological changes. Expressions of TNF-α and IL-18 were suppressed by GLA in plasma. The levels of SPA, MDA and NO in lung were down-regulated significantly in groups administrated with GLA. While the SOD level increased after GLA administration. Additionally, the attenuation of inflammatory responses by GLA was closely associated with p38MAPK/ERK pathway, and the expressions of protein p-p38MAPK and pERK were inhibited by GLA in LPS-induced ARDS rats.

MATERIALS AND METHODS: Sixty-four Wistar rats were randomly assigned into control group, Glabridin (GLA) alone group, LPS groups (6 h, 12 h, 24 h), GLA with LPS groups (6 h, 12 h, 24 h). ARDS was induced in rats by intraperitoneal administration of LPS (10 mg/kg). The degree of lung edema was evaluated by calculating the wet/dry weight ratio. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were assayed by enzyme-linked immunosorbent assay (ELISA). Surfactant protein A (SPA), malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) were analyzed. Pathological changes of lung tissues were observed by H&E staining. The protein expression of p38MAPK and ERK was detected using immunohistochemical techniques. Lung phosphorylated p38MAPK (p-p38MAPK) and pERK protein expression changes were detected by Western blotting.

CONCLUSIONS: Glabridin significantly ameliorated the lung injury induced by LPS in rats via the inhibition of p38MAPK and ERK signaling pathway, antioxidant effect and reducing inflammation.