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


METHODS
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.


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.


CONCLUSIONS
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.
Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
Tzu-Ling
TL
Tseng
Mei-Fang
MF
Chen
Ming-Jen
MJ
Tsai
Yung-Hsiang
YH
Hsu
Chin-Piao
CP
Chen
Tony J F
TJ
Lee
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D005419:Flavonoids / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D007118:Immunoassay; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one