Taraxasterol inhibits cigarette smoke-induced lung inflammation by inhibiting reactive oxygen species-induced TLR4 trafficking to lipid rafts

Eur J Pharmacol. 2016 Oct 15;789:301-307. doi: 10.1016/j.ejphar.2016.07.047. Epub 2016 Jul 28.

Abstract

Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been demonstrated to have anti-inflammatory effects. However, the protective effects of taraxasterol against cigarette smoke (CS)-induced lung inflammation have not been reported. This study aimed to investigate the protective effects and mechanism of taraxasterol on CS-induced lung inflammation in mice. CS-induced mouse lung inflammation model was used to investigate the protective effects of taraxasterol in vivo. Human bronchial epithelial cells (HBECs) were used to investigate the protective mechanism of taraxasterol in vitro. The results showed that taraxasterol attenuated CS-induced lung pathological changes, inflammatory cells infiltration, inflammatory cytokines TNF-α, IL-6 and IL-1β production. Taraxasterol also up-regulated CS-induced glutathione (GSH) production. In vitro, taraxasterol was found to inhibit CS-induced reactive oxygen species production, recruitment of TLR4 into lipid rafts, NF-κB activation, and IL-8 production. Furthermore, our results showed that antioxidant N-acetyl-L-cysteine (NAC) significantly inhibited CS-induced recruitment of TLR4 into lipid rafts as well as IL-8 production. In conclusion, our results suggested that taraxasterol had protective effects of CS-induced lung inflammation.

Keywords: Cigarette smoke; Lipid raft; Reactive oxygen species; TLR4; Taraxasterol.

MeSH terms

  • Actins / metabolism
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokines / biosynthesis
  • Glutathione / metabolism
  • Humans
  • Interleukin-8 / biosynthesis
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Male
  • Membrane Microdomains / drug effects*
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism
  • Pneumonia / drug therapy*
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Protein Transport / drug effects
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Smoke / adverse effects*
  • Sterols / pharmacology*
  • Sterols / therapeutic use
  • Tobacco Products*
  • Toll-Like Receptor 4 / metabolism*
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use

Substances

  • Actins
  • Chemokines
  • Interleukin-8
  • NF-kappa B
  • Reactive Oxygen Species
  • Smoke
  • Sterols
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Triterpenes
  • NF-KappaB Inhibitor alpha
  • taraxasterol
  • Glutathione