title: Dietary α-eleostearic acid ameliorates experimental inflammatory bowel disease in mice by activating peroxisome proliferator-activated receptor-γ.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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
  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.
authors: Genetics, Bioinformatics, and Computational Biology Program, Virginia Tech, Blacksburg, Virginia, United States of America. snl@vt.edu
authors: Stephanie N
authors: SN
authors: Lewis
authors: Lera
authors: L
authors: Brannan
authors: Amir J
authors: AJ
authors: Guri
authors: Pinyi
authors: P
authors: Lu
authors: Raquel
authors: R
authors: Hontecillas
authors: Josep
authors: J
authors: Bassaganya-Riera
authors: David R
authors: DR
authors: Bevan
mesh_terms: D000818:Animals; D002460:Cell Line; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism*; D008042:Linolenic Acids / Q000627:therapeutic use*; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D008042:Linolenic Acids; D047495:PPAR gamma; C004934:eleostearic acid