Protective effect of EC-18, a synthetic monoacetyldiglyceride on lung inflammation in a murine model induced by cigarette smoke and lipopolysaccharide

Int Immunopharmacol. 2016 Jan:30:62-68. doi: 10.1016/j.intimp.2015.11.025. Epub 2015 Dec 1.

Abstract

The antler of Sika deer (Cervus nippon Temminck) has been used a natural medicine in Korea, China and Japan, and a monoacetyldiaglyceride (1-palmitoyl-2-linoleoyl-3-acetylglycerol, PLAG) was found in the antler of Sika deer as a constituent for immunomodulation. In this study, we investigated protective effects of EC-18 (a synthetic copy of PLAG) on inflammatory responses using a cigarette smoke with lipopolysaccharide (LPS)-induced airway inflammation model. Mice were exposed to cigarette smoke for 1h per day for 3days. Ten micrograms of LPS dissolved in 50μL of PBS was administered intra nasally 1h after the final cigarette smoke exposure. EC-18 was administered by oral gavage at doses of 30 and 60mg/kg for 3days. EC-18 significantly reduced the number of neutrophils, reactive oxygen species production, cytokines and elastase activity in bronchoalveolar lavage fluid (BALF) compared with the cigarette smoke and LPS induced mice. Histologically, EC-18 attenuated airway inflammation with a reduction in myeloperoxidase expression in lung tissue. Additionally, EC-18 inhibited the phosphorylation of NF-κB and IκB induced by cigarette smoke and LPS exposure. Our results show that EC-18 effectively suppresses neutrophilic inflammation induced by cigarette smoke and LPS exposure. In conclusion, this study suggests that EC-18 has therapeutic potential for the treatment of chronic obstructive pulmonary disease.

Keywords: Chronic obstructive pulmonary disease; Cigarette smoke; EC-18; Lung inflammation; Monoacetyldiaglyceride.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Antlers / metabolism
  • Cell Movement / drug effects
  • Cytokines / metabolism
  • Deer / immunology
  • Diglycerides / administration & dosage*
  • Diglycerides / chemical synthesis
  • Diglycerides / isolation & purification
  • Humans
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Pneumonia / drug therapy*
  • Pneumonia / immunology
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Reactive Oxygen Species / metabolism
  • Smoking / adverse effects

Substances

  • 1-palmitoyl-2-linoleoyl-3-acetyl-rac glycerol
  • Anti-Inflammatory Agents
  • Cytokines
  • Diglycerides
  • Inflammation Mediators
  • Lipopolysaccharides
  • Reactive Oxygen Species