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

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.
AuthorsTianzhu Zhang, Jing Wang, Shumin Wang, Chunhua Ma
JournalToxicology mechanisms and methods (Toxicol Mech Methods) Vol. 25 Issue 9 Pg. 665-71 ( 2015) ISSN: 1537-6524 [Electronic] England
PMID26540118 (Publication Type: Journal Article)
Chemical References
  • 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
Topics
  • Acute Lung Injury (chemically induced, metabolism, pathology, prevention & control)
  • Animals
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid (cytology, immunology)
  • Cytokines (metabolism)
  • Lipopolysaccharides (toxicity)
  • Lung (drug effects, immunology, metabolism, pathology)
  • Male
  • Mice, Inbred BALB C
  • Saponins (administration & dosage, therapeutic use)
  • Signal Transduction (drug effects)
  • Steroids (administration & dosage, therapeutic use)
  • Toll-Like Receptor 2 (antagonists & inhibitors)
  • Toll-Like Receptor 4 (antagonists & inhibitors)
  • Transcription Factor RelA (antagonists & inhibitors)

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