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

• Published in: International immunopharmacology Vol. 40; pp. 219 - 228
• Main Authors: Yang, Shengqian, Yu, Ziru, Yuan, Tianyi, Wang, Lin, Wang, Xue, Yang, Haiguang, Sun, Lan, Wang, Yuehua, Du, Guanhua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2016; Elsevier BV
• Subjects: Acute lung injury; Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Arthritis; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Cell Count; Collagen; Cytokines - blood; Cytokines - metabolism; Edema; In vitro methods and tests; In vivo methods and tests; Infiltration; Inflammation; Injuries; Interleukin 6; Lactose - analogs & derivatives; Lactose - pharmacology; Lactose - therapeutic use; Lipopolysaccharide; Lipopolysaccharides; Lung - drug effects; Lung - metabolism; Lung - pathology; Lungs; Male; MAP Kinase Kinase Kinases - antagonists & inhibitors; MAP Kinase Kinase Kinases - metabolism; Medical treatment; Methyl salicylate 2-O-β-d-lactoside; Mice; Mice, Inbred BALB C; Molecular modelling; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Nuclear transport; Peroxidase - metabolism; Pharmacology; Phosphorylation; Phosphorylation - drug effects; RAW 264.7 Cells; Respiratory diseases; Salicylates - pharmacology; Salicylates - therapeutic use; Salicylic acid; TAK1; TAK1 protein; Tissues; Translocation; Lipopolysaccharide; Methyl salicylate 2-O-β-d-lactoside; Acute lung injury; NF-κB; NLRP3; TAK1
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2016.08.041

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. •Methyl salicylate 2-O-β-d-lactoside (MSL) markedly ameliorates pulmonary edema.•MSL significantly decreases cellular infiltration in lung tissue.•MSL significantly inhibits inflammatory response in LPS-induced ALI mice.•MSL inhibits TAK1/NF-κB phosphorylation and NLRP3 expression in lung tissue.•MSL exhibits a therapeutic effect on LPS-induced ALI.