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      Suppression of lung inflammation in an LPS-induced acute lung injury model by the fruit hull of Gleditsia sinensis

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          Abstract

          Background

          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. Here, we explored FGS as a possible therapeutics against inflammatory lung diseases including ALI, and examined an underlying mechanism for the effect of FGS.

          Methods

          The 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.

          Results

          Bioluminescence 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.

          Conclusions

          FGS 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 material

          The online version of this article (doi:10.1186/1472-6882-14-402) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress.

          A major mechanism in the cellular defense against oxidative or electrophilic stress is activation of the Nrf2-antioxidant response element signaling pathway, which controls the expression of genes whose protein products are involved in the detoxication and elimination of reactive oxidants and electrophilic agents through conjugative reactions and by enhancing cellular antioxidant capacity. At the molecular level, however, the regulatory mechanisms involved in mediating Nrf2 activation are not fully understood. It is well established that Nrf2 activity is controlled, in part, by the cytosolic protein Keap1, but the nature of this pathway and the mechanisms by which Keap1 acts to repress Nrf2 activity remain to be fully characterized and are the topics of discussion in this minireview. In addition, a possible role of the Nrf2-antioxidant response element transcriptional pathway in neuroprotection will also be discussed.
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            Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice

            Oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect in antioxidant responses has been speculated to exacerbate asthma severity, this has been difficult to demonstrate with certainty. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive basic leucine zipper transcription factor that is involved in the transcriptional regulation of many antioxidant genes. We show that disruption of the Nrf2 gene leads to severe allergen-driven airway inflammation and hyperresponsiveness in mice. Enhanced asthmatic response as a result of ovalbumin sensitization and challenge in Nrf2-disrupted mice was associated with more pronounced mucus cell hyperplasia and infiltration of eosinophils into the lungs than seen in wild-type littermates. Nrf2 disruption resulted in an increased expression of the T helper type 2 cytokines interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid and in splenocytes after allergen challenge. The enhanced severity of the asthmatic response from disruption of the Nrf2 pathway was a result of a lowered antioxidant status of the lungs caused by lower basal expression, as well as marked attenuation, of the transcriptional induction of multiple antioxidant genes. Our studies suggest that the responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma.
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              Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke–induced emphysema in mice

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                Author and article information

                Contributors
                kyunhakim@pusan.ac.kr
                kmj1205@hanmail.net
                yeast10@hanmail.net
                hagis@pusan.ac.kr
                kmd@pusan.ac.kr
                mjoo@pusan.ac.kr
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                15 October 2014
                15 October 2014
                2014
                : 14
                : 1
                : 402
                Affiliations
                [ ]School of Korean Medicine, Pusan National University, Yangsan, 626-870 Republic of Korea
                [ ]Korean Medicine Hospital, Pusan National University, Yangsan, 626-870 Republic of Korea
                [ ]Department of Korean Medical Science, Pusan National University, Yangsan, 626-870 Republic of Korea
                [ ]Department of Korean Medical Science and Korean Medicine Hospital, Pusan National University, Yangsan, 626-870 Republic of Korea
                Article
                1968
                10.1186/1472-6882-14-402
                4203922
                25318387
                de17ffd4-7840-46c5-8853-aca8b4cd52b5
                © Kim et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 4 March 2013
                : 7 October 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Complementary & Alternative medicine
                gleditsia sinensis,traditional asian medicine,therapeutics,acute lung inflammation,nrf2

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