Abstract
BackgroundThe fruit hull of Gleditsia sinensis (FGS) used in traditional Asian medicine was reported to have a preventive effect on lung inflammation in an acute lung injury (ALI) mouse model. Here, we explored FGS as a possible therapeutics against inflammatory lung diseases including ALI, and examined an underlying mechanism for the effect of FGS.MethodsThe decoction of FGS in water was prepared and fingerprinted. Mice received an intra-tracheal (i.t.) FGS 2 h after an intra-peritoneal (i.p.) injection of lipopolysaccharide (LPS). The effect of FGS on lung inflammation was determined by chest imaging of NF-κB reporter mice, counting inflammatory cells in bronchoalveolar lavage fluid, analyzing lung histology, and performing semi-quantitative RT-PCR analysis of lung tissue. Impact of Nrf2 on FGS effect was assessed by comparing Nrf2 knockout (KO) and wild type (WT) mice that were treated similarly.ResultsBioluminescence from the chest of the reporter mice was progressively increased to a peak at 16 h after an i.p. LPS treatment. FGS treatment 2 h after LPS reduced the bioluminescence and the expression of pro-inflammatory cytokine genes in the lung. While suppressing the infiltration of inflammatory cells to the lungs of WT mice, FGS post-treatment failed to reduce lung inflammation in Nrf2 KO mice. FGS activated Nrf2 and induced Nrf2-dependent gene expression in mouse lung.ConclusionsFGS post-treatment suppressed lung inflammation in an LPS-induced ALI mouse model, which was mediated at least in part by Nrf2. Our results suggest a therapeutic potential of FGS on inflammatory lung diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-402) contains supplementary material, which is available to authorized users.
Highlights
The fruit hull of Gleditsia sinensis (FGS) used in traditional Asian medicine was reported to have a preventive effect on lung inflammation in an acute lung injury (ALI) mouse model
FGS post-treatment suppresses lung inflammation in an LPS-induced ALI mouse model Given the previous report that pretreatment with FGS suppresses lung inflammation in an LPS-induced ALI mouse model, we sought to test whether FGS has a therapeutic potential against inflammatory lung diseases
We needed to set up a new mouse model because most studies on the effect of a traditional medicine rely on feeding with an herbal medicine for a while prior to the onset of diseases, which address not a therapeutic, but rather preventive, effect of the medicine [22]
Summary
Preparation of the water extract of G. sinensis fruit hull The fruits of G. sinensis were purchased from KwangMyoung-Dang herb store (Pusan, Republic of Korea), and authenticated by Professor C.W. Animal model for acute lung injury and FGS administration All experimental procedures followed the NIH of Korea Guidelines for the Care and Use of Laboratory Animals, and all the experiments were approved by the Institutional Animal Care and Use Committee of Pusan National University (protocol number: PNU-2010-00028). Mice were anesthetized by Zoletil (Virbac, Carros cedex, France), and received a single dose of 10 mg LPS (Escherichia coli O55: B5 from Sigma, St. Louis, MO, USA) /kg body weight or sterile saline via intra-peritoneal (i.p.) route. At 2 h after i.p. LPS administration, FGS (150 μg/kg of body weight) in 25 μl of PBS was loaded in a micro-sprayer (Model IA-1C, Penn-Century Inc., USA) and delivered in aerosol to the lung via trachea under visual guidance. P values less than 0.05 were considered statistically significant
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