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The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice
BACKGROUND: Guettarda speciosa is mainly found in tropical areas in Asia. Although G. speciosa is traditionally used to treat some of the inflammatory disorders, the experimental evidence supporting the anti-inflammatory effect of G. speciosa is limited. Here, we sought to obtain evidence that G. sp...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076890/ https://www.ncbi.nlm.nih.gov/pubmed/32033557 http://dx.doi.org/10.1186/s12906-020-2828-6 |
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author | Kim, Kyun Ha Lee, Ji Yeon Ahn, Seonju Won, Ran Kim, Sang-Jun Jeong, Seung-Il Lee, Jung Ju Kim, Jong-In Choi, Jun-Yong Joo, Myungsoo |
author_facet | Kim, Kyun Ha Lee, Ji Yeon Ahn, Seonju Won, Ran Kim, Sang-Jun Jeong, Seung-Il Lee, Jung Ju Kim, Jong-In Choi, Jun-Yong Joo, Myungsoo |
author_sort | Kim, Kyun Ha |
collection | PubMed |
description | BACKGROUND: Guettarda speciosa is mainly found in tropical areas in Asia. Although G. speciosa is traditionally used to treat some of the inflammatory disorders, the experimental evidence supporting the anti-inflammatory effect of G. speciosa is limited. Here, we sought to obtain evidence that G. speciosa has anti-inflammatory activity using an acute lung injury (ALI) mouse model and to explore possible underlying mechanisms for the activity. METHODS: The methanol extract of G. speciosa Linn. (MGS) was fingerprinted by HPLC. Cytotoxicity was determined by MTT and flow cytometer. As for an ALI mouse model, C57BL/6 mice received an intratracheal (i.t.) injection of lipopolysaccharide (LPS). The effects of MGS on lung inflammation in the ALI mice were assessed by differential cell counting and FACS of inflammatory cells and hematoxylin and eosin staining of lung tissue. Proteins were analyzed by immunoprecipitation and immunoblotting, and gene expression was by real-time qPCR. Neutrophil elastase activity was measured by ELISA. RESULTS: MGS did not cause metabolic disarray or produce reactive oxygen species that could induce cytotoxicity. Similar to ALI patients, C57BL/6 mice that received an i.t. LPS developed a high level of neutrophils, increased pro-inflammatory cytokines, and inflicted tissue damage in the lung, which was suppressed by i.t. MGS administered at 2 h after LPS. Mechanistically, MGS activated Nrf2, which was related to MGS interrupting the ubiquitin-dependent degradation of Nrf2. MGS suppressed the nuclear localization of NF-κB induced by LPS, suggesting the inhibition of NF-κB activity. Furthermore, MGS inhibited the enzymatic activity of neutrophil elastase. CONCLUSION: MGS could suppress lung inflammation in an ALI mouse model, the effect of which could be attributed to multiple mechanisms, including the activation of Nrf2 and the suppression of NF-κB and neutrophil elastase enzymatic activity by MGS. |
format | Online Article Text |
id | pubmed-7076890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-70768902020-03-19 The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice Kim, Kyun Ha Lee, Ji Yeon Ahn, Seonju Won, Ran Kim, Sang-Jun Jeong, Seung-Il Lee, Jung Ju Kim, Jong-In Choi, Jun-Yong Joo, Myungsoo BMC Complement Med Ther Research Article BACKGROUND: Guettarda speciosa is mainly found in tropical areas in Asia. Although G. speciosa is traditionally used to treat some of the inflammatory disorders, the experimental evidence supporting the anti-inflammatory effect of G. speciosa is limited. Here, we sought to obtain evidence that G. speciosa has anti-inflammatory activity using an acute lung injury (ALI) mouse model and to explore possible underlying mechanisms for the activity. METHODS: The methanol extract of G. speciosa Linn. (MGS) was fingerprinted by HPLC. Cytotoxicity was determined by MTT and flow cytometer. As for an ALI mouse model, C57BL/6 mice received an intratracheal (i.t.) injection of lipopolysaccharide (LPS). The effects of MGS on lung inflammation in the ALI mice were assessed by differential cell counting and FACS of inflammatory cells and hematoxylin and eosin staining of lung tissue. Proteins were analyzed by immunoprecipitation and immunoblotting, and gene expression was by real-time qPCR. Neutrophil elastase activity was measured by ELISA. RESULTS: MGS did not cause metabolic disarray or produce reactive oxygen species that could induce cytotoxicity. Similar to ALI patients, C57BL/6 mice that received an i.t. LPS developed a high level of neutrophils, increased pro-inflammatory cytokines, and inflicted tissue damage in the lung, which was suppressed by i.t. MGS administered at 2 h after LPS. Mechanistically, MGS activated Nrf2, which was related to MGS interrupting the ubiquitin-dependent degradation of Nrf2. MGS suppressed the nuclear localization of NF-κB induced by LPS, suggesting the inhibition of NF-κB activity. Furthermore, MGS inhibited the enzymatic activity of neutrophil elastase. CONCLUSION: MGS could suppress lung inflammation in an ALI mouse model, the effect of which could be attributed to multiple mechanisms, including the activation of Nrf2 and the suppression of NF-κB and neutrophil elastase enzymatic activity by MGS. BioMed Central 2020-02-07 /pmc/articles/PMC7076890/ /pubmed/32033557 http://dx.doi.org/10.1186/s12906-020-2828-6 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Kim, Kyun Ha Lee, Ji Yeon Ahn, Seonju Won, Ran Kim, Sang-Jun Jeong, Seung-Il Lee, Jung Ju Kim, Jong-In Choi, Jun-Yong Joo, Myungsoo The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice |
title | The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice |
title_full | The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice |
title_fullStr | The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice |
title_full_unstemmed | The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice |
title_short | The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice |
title_sort | methanol extract of guettarda speciosa linn. ameliorates acute lung injury in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076890/ https://www.ncbi.nlm.nih.gov/pubmed/32033557 http://dx.doi.org/10.1186/s12906-020-2828-6 |
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