Zerumbone reduced the inflammatory response of acute lung injury in endotoxin-treated mice via Akt-NFκB pathway

Chem Biol Interact. 2017 Jun 1:271:9-14. doi: 10.1016/j.cbi.2017.04.017. Epub 2017 Apr 22.

Abstract

Zerumbone, a cyclic eleven-membered sesquiterpene, is the major component of the essential oil isolated from the wild ginger, Zingiber zerumbet. There are several beneficial pharmacological activities of zerumbone including anti-inflammatory, antioxidant, and anticancer activities. Acute lung injury (ALI) is an acute pulmonary inflammatory disorder with high morbidity and mortality rate. In present study, we aimed to investigate the protective effects and mechanisms of zerumbone on endotoxin, lipopolysaccharide (LPS)-induced ALI. Mice were pretreated with zerumbone at various concentrations for 30 min followed by intratracheal administration of LPS for 6 h. Pretreatment with zerumbone not only reduced leukocytes infiltration into the alveolar space but also inhibited lung edema in LPS-induced ALI. Decreased secretion of proinflammatory cytokines such as TNFα and IL-6 caused by LPS were reversed by zerumbone. LPS-induced expressions of proinflammatory mediators, iNOS and COX-2, were inhibited by zerumbone. In addition, NFκB activation and Akt phosphorylation were inhibited by zerumbone in LPS-induced ALI. All these results suggested that the protective mechanisms of zerumbone on endotoxin-induced ALI were via inhibition of Akt-NFκB activation.

Keywords: Acute lung injury; Akt-NFκB; Endotoxin; Proinflammatory mediators; Zerumbone.

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / physiopathology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Disease Models, Animal
  • Endotoxins / toxicity*
  • Enzyme Activation / drug effects
  • Inflammation / prevention & control
  • Male
  • Mice
  • NF-kappa B / metabolism*
  • Oncogene Protein v-akt / metabolism
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects*
  • Zingiber officinale / chemistry

Substances

  • Anti-Inflammatory Agents
  • Endotoxins
  • NF-kappa B
  • Sesquiterpenes
  • zerumbone
  • Oncogene Protein v-akt