Phytochemical drug candidates for the modulation of peroxisome proliferator‐activated receptor γ in inflammatory bowel diseases

2020 ◽  
Vol 34 (7) ◽  
pp. 1530-1549 ◽  
Author(s):  
Balaji Venkataraman ◽  
Shreesh Ojha ◽  
Prasanna D. Belur ◽  
Bhoomendra Bhongade ◽  
Vishnu Raj ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Drug Candidates ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals In Vitro Evaluation of the Phytopharmacological Potential of Sargassum incisifolium for the Treatment of Inflammatory Bowel Diseases

Medicines ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 49 ◽  
Author(s):  
Mutenta Nyambe ◽  
Trevor Koekemoer ◽  
Maryna van de Venter ◽  
Eleonora Goosen ◽  
Denzil Beukes
Keyword(s):  
Inflammatory Bowel Diseases ◽  
In Vitro Assays ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Bowel Diseases ◽  
Anti Oxidant ◽  
Inflammatory Bowel ◽  
Gastro Intestinal Tract

Background: Comprised of Crohn’s disease and ulcerative colitis, inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastro-intestinal tract, which often results in severe damage to the intestinal mucosa. This study investigated metabolites from the South African endemic alga, Sargassum incisifolium, as potential treatments for IBD. Phytochemical evaluation of S. incisifolium yielded prenylated toluhydroquinones and toluquinones, from which semi-synthetic analogs were derived, and a carotenoid metabolite. The bioactivities of S. incisifolium fractions, natural products, and semi-synthetic derivatives were evaluated using various in vitro assays. Methods: Sargahydroquinoic acid isolated from S. incisifolium was converted to several structural derivatives by semi-synthetic modification. Potential modulation of IBD by S. incisifolium crude fractions, natural compounds, and sargahydroquinoic acid analogs was evaluated through in vitro anti-inflammatory activity, anti-oxidant activity, cytotoxicity against HT-29 and Caco-2 colorectal cancer cells, and PPAR-γ activation. Results: Sargahydroquinoic acid acts on various therapeutic targets relevant to IBD treatment. Conclusions: Conversion of sargahydroquinoic acid to sarganaphthoquinoic acid increases peroxisome proliferator activated receptor gamma (PPAR-γ) activity, compromises anti-oxidant activity, and has no effect on cytotoxicity against the tested cell lines.

scholarly journals Pharmacological Evaluation of the SCID T Cell Transfer Model of Colitis: As a Model of Crohn's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Thomas Lindebo Holm ◽  
Steen Seier Poulsen ◽  
Helle Markholst ◽  
Stine Reedtz-Runge
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adoptive Transfer ◽  
Inflammatory Bowel Diseases ◽  
Transfer Model ◽  
Drug Candidates ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
T Cell Transfer ◽  
Colitis Model

Animal models are important tools in the development of new drug candidates against the inflammatory bowel diseases (IBDs) Crohn's disease and ulcerative colitis. In order to increase the translational value of these models, it is important to increase knowledge relating to standard drugs. Using the SCID adoptive transfer colitis model, we have evaluated the effect of currently used IBD drugs and IBD drug candidates, that is, anti-TNF-α, TNFR-Fc, anti-IL-12p40, anti-IL-6, CTLA4-Ig, anti-α4β7 integrin, enrofloxacin/metronidazole, and cyclosporine. We found that anti-TNF-α, antibiotics, anti-IL-12p40, anti-α4β7 integrin, CTLA4-Ig, and anti-IL-6 effectively prevented onset of colitis, whereas TNFR-Fc and cyclosporine did not. In intervention studies, antibiotics, anti-IL-12p40, and CTLA4-Ig induced remission, whereas the other compounds did not. The data suggest that the adoptive transfer model and the inflammatory bowel diseases have some main inflammatory pathways in common. The finding that some well-established IBD therapeutics do not have any effect in the model highlights important differences between the experimental model and the human disease.

scholarly journals Peroxisome Proliferator-Activated Receptors: Experimental Targeting for the Treatment of Inflammatory Bowel Diseases

2020 ◽  
Vol 11 ◽  
Author(s):  
Juan Decara ◽  
Patricia Rivera ◽  
Antonio Jesús López-Gambero ◽  
Antonia Serrano ◽  
Francisco Javier Pavón ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Peroxisome Proliferator ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ

2005 ◽  
Vol 201 (8) ◽  
pp. 1205-1215 ◽  
Author(s):  
Christel Rousseaux ◽  
Bruno Lefebvre ◽  
Laurent Dubuquoy ◽  
Philippe Lefebvre ◽  
Olivier Romano ◽  
...  
Keyword(s):  
Antiinflammatory Drug ◽  
Peroxisome Proliferator ◽  
Aminosalicylic Acid ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Peroxisome Proliferator Response Element ◽  
Antiinflammatory Effects

5-aminosalicylic acid (5-ASA) is an antiinflammatory drug widely used in the treatment of inflammatory bowel diseases. It is known to inhibit the production of cytokines and inflammatory mediators, but the mechanism underlying the intestinal effects of 5-ASA remains unknown. Based on the common activities of peroxisome proliferator–activated receptor-γ (PPAR-γ) ligands and 5-ASA, we hypothesized that this nuclear receptor mediates 5-ASA therapeutic action. To test this possibility, colitis was induced in heterozygous PPAR-γ+/− mice and their wild-type littermates, which were then treated with 5-ASA. 5-ASA treatment had a beneficial effect on colitis only in wild-type and not in heterozygous mice. In epithelial cells, 5-ASA increased PPAR-γ expression, promoted its translocation from the cytoplasm to the nucleus, and induced a modification of its conformation permitting the recruitment of coactivators and the activation of a peroxisome-proliferator response element–driven gene. Validation of these results was obtained with organ cultures of human colonic biopsies. These data identify PPAR-γ as a target of 5-ASA underlying antiinflammatory effects in the colon.

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