Timosaponin B-II inhibits lipopolysaccharide-induced acute lung toxicity via TLR/NF-κB pathway

Toxicol Mech Methods. 2015;25(9):665-71. doi: 10.3109/15376516.2015.1045652. Epub 2015 Nov 5.

Abstract

Timosaponin B-II (TB), a main bioactive compound in Anemarrhena asphodeloides Bunge, has various kinds of pharmacological activities, the present study aimed to investigate the protective role of TB on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS, and TB (20 and 60 mg/kg) was given orally 1 h prior to LPS administration. After 6 h, bronchoalveolar lavagefluid (BALF) and lung tissue were collected. TB decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity. In addition, TB inhibited inflammatory cells and cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in BALF. Furthermore, we demonstrated that TB inhibited the Toll-like receptor-2 (TLR2), Toll-like receptor-4 (TLR4), myeloid differentiation primary response gene-88 (MyD88), nuclear factor-κB (NF-κB) p65 in LPS-induced ALI. These results showed that administration of TB prior to LPS improves ALI, possibly mediating ALI through suppressing TLR/NF-κB pathway activation.

Keywords: Lipopolysaccharide; TLR/NF-κB pathway; lung injury; timosaponin B-II.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / metabolism
  • Lipopolysaccharides / toxicity*
  • Lung / drug effects
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice, Inbred BALB C
  • Saponins / administration & dosage
  • Saponins / therapeutic use*
  • Signal Transduction / drug effects
  • Steroids / administration & dosage
  • Steroids / therapeutic use*
  • Toll-Like Receptor 2 / antagonists & inhibitors*
  • Toll-Like Receptor 4 / antagonists & inhibitors*
  • Transcription Factor RelA / antagonists & inhibitors*

Substances

  • Cytokines
  • Lipopolysaccharides
  • Saponins
  • Steroids
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • lipopolysaccharide, E coli O55-B5
  • timosaponin B-II