Oroxylin-A rescues LPS-induced acute lung injury via regulation of NF-κB signaling pathway in rodents

PLoS One. 2012;7(10):e47403. doi: 10.1371/journal.pone.0047403. Epub 2012 Oct 10.

Abstract

Background and purpose: Successful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. This study was designed to assess the beneficial effects of post-treatment of oroxylin A (OroA), a flavonoid, in ameliorating lipopolysaccharides (LPS)-induced lung inflammation and fatality.

Experimental approach: Rats were injected with LPS (10 mg/kg, iv) to induce ALI, and OroA was given (15 mg/kg, iv) 1 hr or 6 hrs after LPS challenge. Twenty four hrs after LPS challenge, biochemical changes in the blood and lung tissues, and morphological/histological alterations in the lung associated with inflammation and injury were examined. Therapeutic effect of OroA was assessed by measuring the survival rate in endotoxemic mice.

Key results: LPS (10 mg/kg, iv) significantly altered WBC counts, elevated plasma tumor necrosis factor (TNF)-α and nitric oxide (NO), increased pulmonary edema, thickened alveolar septa, and decreased survival rate. These changes were ameliorated by OroA (15 mg/kg, iv) administered 1 hr or 6 hrs after LPS challenge. This post-treatment also significantly attenuated LPS-induced activation of nuclear factor-κB (NF-κB) and the release of high mobility group box 1 (HMGB1) in lung tissues. Furthermore, post-treatment with OroA (60 mg/kg, ip) administered 1 hr or 6 hrs after LPS challenge in mice significantly increased survival rate.

Conclusion and implication: OroA administered after induction of ALI by LPS significantly prevent and revere lung tissues injuries with increased survival rate. Positive post-treatment effects of OroA suggest that OroA is a potentially useful candidate for managing lung inflammation in LPS-induced endotoxemia and septic shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / pathology
  • Analysis of Variance
  • Animals
  • Flavonoids / therapeutic use*
  • Fluorescent Antibody Technique
  • Immunoassay
  • Immunohistochemistry
  • Leukocyte Count
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • NF-kappa B / metabolism*
  • Nitric Oxide / blood
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology*
  • Survival Analysis
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Flavonoids
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one

Grants and funding

Tzu-Chi University Grants TCMRC-C95005-01, TCRPP99006, TCIRP 98005-01 and TCIRP 98005-02, and National Science Council of Taiwan Grants NSC-NSC-95-2320-B-320-013-MY2, NSC-96-2320-B-320-005-MY3 and NSC 100-2320-B-320-007-MY2, Buddhist Tzu Chi General Hospital Grant TCRD98-34, and the Tzu Chi Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.