Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression.

Acute lung injury (ALI)， characterized by pulmonary edema and inflammatory cell infiltration， is a common syndrome of acute hypoxemic respiratory failure. Methyl salicylate 2-O-β-d-lactoside (MSL)， a natural derivative of salicylate extracted from Gaultheria yunnanensis (Franch.) Rehder， was reported to have potent anti-inflammatory effects on the progression of collagen or adjuvant-induced arthritis in vivo and in vitro. The aim of this study is to investigate the therapeutic effect of MSL on lipopolysaccharide (LPS)-induced acute lung injury and reveal underlying molecular mechanisms. Our results showed that MSL significantly ameliorated pulmonary edema and histological severities， and inhibited IL-6 and IL-1β production in LPS-induced ALI mice. MSL also reduced MPO activity in lung tissues and the number of inflammatory cells in BALF. Moreover， we found that MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation， as well as the expression of NLRP3 protein in lung tissues. Furthermore， MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation in Raw264.7 cells. In addition， MSL significantly inhibited nuclear translocation of NF-κB p65 in cells treated with LPS in vitro. Taken together， our results suggested that MSL exhibited a therapeutic effect on LPS-induced ALI by inhibiting TAK1/NF-κB phosphorylation and NLRP3 expression.