Dietary alpha-Eleostearic Acid Ameliorates Experimental Inflammatory Bowel Disease in Mice by Activating Peroxisome Proliferator-Activated Receptor-gamma

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dc.contributor.authorLewis, Stephanie N.en
dc.contributor.authorBrannan, Leraen
dc.contributor.authorGuri, Amir J.en
dc.contributor.authorLu, Pinyien
dc.contributor.authorHontecillas, Raquelen
dc.contributor.authorBassaganya-Riera, Josepen
dc.contributor.authorBevan, David R.en
dc.date.accessioned2016-12-23T14:38:17Zen
dc.date.available2016-12-23T14:38:17Zen
dc.date.issued2011-08-31en
dc.description.abstractBackground: Treatments for inflammatory bowel disease (IBD) are modestly effective and associated with side effects from prolonged use. As there is no known cure for IBD, alternative therapeutic options are needed. Peroxisome proliferator-activated receptor-gamma (PPARγ) has been identified as a potential target for novel therapeutics against IBD. For this project, compounds were screened to identify naturally occurring PPARγ agonists as a means to identify novel anti-inflammatory therapeutics for experimental assessment of efficacy. Methodology/Principal Findings: Here we provide complementary computational and experimental methods to efficiently screen for PPARγ agonists and demonstrate amelioration of experimental IBD in mice, respectively. Computational docking as part of virtual screening (VS) was used to test binding between a total of eighty-one compounds and PPARγ. The test compounds included known agonists, known inactive compounds, derivatives and stereoisomers of known agonists with unknown activity, and conjugated trienes. The compound identified through VS as possessing the most favorable docked pose was used as the test compound for experimental work. With our combined methods, we have identified α-eleostearic acid (ESA) as a natural PPARγ agonist. Results of ligand-binding assays complemented the screening prediction. In addition, ESA decreased macrophage infiltration and significantly impeded the progression of IBD-related phenotypes through both PPARγ-dependent and –independent mechanisms in mice with experimental IBD. Conclusions/Significance: This study serves as the first significant step toward a large-scale VS protocol for natural PPARγ agonist screening that includes a massively diverse ligand library and structures that represent multiple known target pharmacophores.en
dc.description.sponsorshipNIH Biomedical and Behavioral Sciences Research Training Grant R25 GM072767 (Virginia Tech Initiative to Maximize Student Diversity). National Center for Complementary and Alternative Medicine Grant 5R01AT4308. The Genetics, Bioinformatics, and Computational Biology PhD program, Virginia Tech, Blacksburg, VA 24601. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.versionPublished versionen
dc.format.extent? - ? (14) page(s)en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0024031en
dc.identifier.issn1932-6203en
dc.identifier.issue8en
dc.identifier.urihttp://hdl.handle.net/10919/73810en
dc.identifier.volume6en
dc.languageEnglishen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000294680800048&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectobesity-related inflammationen
dc.subjectconjugated triene systemen
dc.subjectprotein data-banken
dc.subjectppar-gammaen
dc.subjectligand-bindingen
dc.subjectpunicic aciden
dc.subjectfatty-acidsen
dc.subjectlipid-peroxidationen
dc.subjectglucose-toleranceen
dc.subjectstructural basisen
dc.titleDietary alpha-Eleostearic Acid Ameliorates Experimental Inflammatory Bowel Disease in Mice by Activating Peroxisome Proliferator-Activated Receptor-gammaen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Biocomplexity Instituteen
pubs.organisational-group/Virginia Tech/University Research Institutes/Biocomplexity Institute/Researchersen
pubs.organisational-group/Virginia Tech/University Research Institutes/Biocomplexity Institute/SelectedFaculty1en

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