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.

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 Role of Peroxisome Proliferator Activated Receptor-gamma and its Ligands in Inflammatory Bowel Disease

1970 ◽  
Vol 1 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Umid Kumar Shrestha ◽  
Bing Xia
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Peroxisome Proliferator ◽  
Aminosalicylic Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Model Studies ◽  
Ppar Γ ◽  
Pubmed Search ◽  
Inflammatory Bowel

Peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor, is highly expressed in the colonic epithelium in contrast to its impaired expression in the patients with ulcerative colitis (UC). Several natural and synthetic ligands of PPAR-γ with some effects in the colon have been identified. The aim of this review is to provide an overview of the role of PPAR-γ and its ligands in inflammatory bowel disease (IBD). Review of article was done using a PubMed search. Animal model studies have revealed that PPAR-γ is the key receptor for 5-aminosalicylic acid that mediates its main effects in the colon. Moreover, the clinical trials have shown that the PPAR-γ agonist rosiglitazone is effective in the treatment of mild to moderately active UC. PPAR-γ gene therapy, used as an adjunct intervention, may be effective in suppressing inflammation in colitis. Some commensal bacteria and natural ligands present in food may induce PPAR-γ expression and activation in the colon which suggest the possibility of associating a natural regulator and a synthetic ligand of PPAR-γ as drug therapy for IBD patients. Further studies are required for the development of unique and effective therapies with PPAR-γ agonists in IBD patients. DOI: http://dx.doi.org/10.3126/jaim.v1i1.5838 Journal of Advances in Internal Medicine. 2012; 1(1): 33-38

scholarly journals Expression of peroxisome proliferator-activated receptor-γ in macrophage suppresses experimentally induced colitis

2007 ◽  
Vol 292 (2) ◽  
pp. G657-G666 ◽  
Author(s):  
Yatrik M. Shah ◽  
Keiichirou Morimura ◽  
Frank J. Gonzalez
Keyword(s):  
Clinical Symptoms ◽  
Body Weight Loss ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Wild Type ◽  
Targeted Disruption ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Cytokine Analysis ◽  
Increased Susceptibility

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has been shown to be a protective transcription factor in mouse models of inflammatory bowel disease (IBD). PPAR-γ is expressed in several different cell types, and mice with a targeted disruption of the PPAR-γ gene in intestinal epithelial cells demonstrated increased susceptibility to dextran sulfate sodium (DSS)-induced IBD. However, the highly selective PPAR-γ ligand rosiglitazone decreased the severity of DSS-induced colitis and suppressed cytokine production in both PPAR-γ intestinal specific null mice and wild-type littermates. Therefore the role of PPAR-γ in different tissues and their contribution to the pathogenesis of IBD still remain unclear. Mice with a targeted disruption of PPAR-γ in macrophages (PPAR-γΔMφ) and wild-type littermates (PPAR-γF/F) were administered 2.5% DSS in drinking water to induce IBD. Typical clinical symptoms were evaluated on a daily basis, and proinflammatory cytokine analysis was performed. PPAR-γΔMφ mice displayed an increased susceptibility to DSS-induced colitis compared with wild-type littermates, as defined by body weight loss, diarrhea, rectal bleeding score, colon length, and histology. IL-1β, CCR2, MCP-1, and inducible nitric oxide synthase mRNA levels in colons of PPAR-γΔMφ mice treated with DSS were higher than in similarly treated PPAR-γF/F mice. The present study has identified a novel protective role for macrophage PPAR-γ in the DSS-induced IBD model. The data suggest that PPAR-γ regulates recruitment of macrophages to inflammatory foci in the colon.

The Role of Peroxisome Proliferator–Activated Receptor γ in Colon Cancer and Inflammatory Bowel Disease

2003 ◽  
Vol 127 (9) ◽  
pp. 1121-1123
Author(s):  
Arthur W. Bull
Keyword(s):  
Inflammatory Bowel Disease ◽  
Colon Cancer ◽  
Bowel Disease ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Inflammatory Bowel

Abstract Objective.—Review the role and therapeutic potential of peroxisome proliferator–activated receptor (PPAR) γ in colonic disorders. Data Sources.—Recent peer-reviewed scientific literature focusing on PPAR γ in the colon. Study Selection.—Research reports using animal models, cultured cell lines, and clinical material were examined for content related to the role of PPAR γ in normal colon cell function, colon cancer, and inflammatory bowel disease. Issues concerned with potential therapeutic use were also considered. Data Synthesis.—Key points pertaining to PPAR function and involvement in colon pathology were extracted and noted. Potential compromises to therapeutic utility are identified. Conclusions.—The emerging important role of PPAR γ in normal tissue homeostasis and pathologic outcomes suggests this receptor is a good candidate as a drug target. Several potential problems with this approach will require further investigation prior to widespread recommendations for modulation of PPAR as an efficacious therapy for cancer, chemoprevention of colon cancer, or treatment of inflammatory bowel disease. The widespread use of PPAR γ ligands for management of type 2 diabetes (such as the glitazone class of drugs including rosiglitazone and pioglitazone) may provide a fortuitous assessment of the efficacy of long-term PPAR modulation.

Primary chemoprevention of endometrial hyperplasia with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone in the PTEN heterozygote murine model

2008 ◽  
Vol 18 (2) ◽  
pp. 329-338 ◽  
Author(s):  
W. Wu ◽  
J. Celestino ◽  
M. R. Milam ◽  
K. M. Schmeler ◽  
R. R. Broaddus ◽  
...  
Keyword(s):  
Cell Lines ◽  
Murine Model ◽  
Endometrial Hyperplasia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Dose Dependent

PTEN mutations have been implicated in the development of endometrial hyperplasia and subsequent cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists have demonstrated antineoplastic and chemopreventive effects. The purpose of this study was to evaluate the effects of the PPAR-γ agonist rosiglitazone on both PTEN wild type and PTEN null cell lines and in the PTEN heterozygote(+/−) murine model. Hec-1-A (PTEN wild type) and Ishikawa (PTEN null) cells were treated with rosiglitazone. Thirty-five female PTEN+/− mice were genotyped and placed into one of four groups for treatment for 18 weeks: A) PTEN wild type with 4 mg/kg rosiglitazone, B) PTEN+/− mice with vehicle, C) PTEN+/− mice with 4 mg/kg rosiglitazone, and D) PTEN+/− mice with 8 mg/kg rosiglitazone. Proliferation and apoptosis were measured by bromodeoxyuridine (BrdU) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of DNA fragmentation sites assay. Rosiglitazone caused cell growth inhibition in both Hec-1-A and Ishikawa in a dose-dependent manner (P< 0.02 and P< 0.03, respectively). Rosiglitazone also induced apoptosis in both Hec-1-A (P< .001) and Ishikawa (P< .001) cells in a dose-dependent manner. In the murine model, rosiglitazone decreased proliferation of the endometrial hyperplastic lesions (B vs C; 39.7% vs 9.3% and B vs D; 39.7% vs 4.2%; P< 0.0001) and increased apoptosis of glandular endometrial epithelial cells (B vs C; 2.8% vs 22.4%; P< 0.0001 and B vs D; 2.8% vs 30.2%; P= 0.003). PPAR-γ agonist rosiglitazone inhibits proliferation and induces apoptosis in both PTEN intact and PTEN null cancer cell lines and in hyperplastic endometrial lesions in the PTEN+/− murine model.

scholarly journals Mesalazine in Inflammatory Bowel Disease: A Trendy Topic Once Again?

2010 ◽  
Vol 24 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Marietta Iacucci ◽  
Shanika de Silva ◽  
Subrata Ghosh
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Peroxisome Proliferator ◽  
Aminosalicylic Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Bowel ◽  
Maintenance Of Remission ◽  
Near Future

5-aminosalicylic acid (5-ASA) preparations (eg, mesalazine, mesalamine) are well-established preparations used in the management of inflammatory bowel disease. These drugs are most useful for the treatment of mild to moderate flares of ulcerative colitis and, especially, for maintenance of remission. Although most gastroenterologists are very familiar with these drugs, the interest in these drugs has undergone a resurgence, with new preparations offering convenience and high dosage, while preserving their customary safety. New dosage regimens are likely to become standard practice in the near future. There is also considerable interest in chemoprevention of colorectal cancer in the context of inflammatory bowel disease, and the role of long-term maintenance therapy with 5-ASAs in achieving such chemoprevention. A mechanism of action for such chemoprevention has been provided by the agonism of the peroxisome proliferator-activated receptor-gamma by 5-ASA, which unifies its efficacy as an anti-inflammatory and chemopreventive agent. In the future, even more effective agents based on 5-ASA are expected, based on more powerful agonism of peroxisome proliferator-activated receptor-gamma; 5-ASA preparations have become ‘trendy’ again.

scholarly journals Peroxisome Proliferator-Activated Receptor-γ Increases Adiponectin Secretion via Transcriptional Repression of Endoplasmic Reticulum Chaperone Protein ERp44

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3195-3203 ◽  
Author(s):  
Qinqiang Long ◽  
Ting Lei ◽  
Bin Feng ◽  
Changjun Yin ◽  
Dan Jin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcriptional Repression ◽  
Energy Homeostasis ◽  
Luciferase Reporter ◽  
Peroxisome Proliferator ◽  
Response Element ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Pparγ Agonist ◽  
Peroxisome Proliferator Response Element

Adiponectin, an adipocyte-derived hormone, is a versatile player involved in the regulation of energy homeostasis, cardiovascular disease, and diabetes. Within adipocytes, adiponectin is retained in the lumen of the endoplasmic reticulum (ER) by binding to the thiol protein ER resident protein 44 kDa (ERp44), which is apparently regulated by the activation of nuclear receptor peroxisome proliferator-activated receptor (PPAR)-γ. However, the precise role of ERp44 in adiponectin secretion remains elusive. In the present study, we investigated the functional correlation between ERp44 and adiponectin in a pig model. The transcription of porcine ERp44 was regulated by PPARγ, which was consistent with the finding of putative peroxisome proliferator response element sites within ERp44 promoter. Using chromatin immunoprecipitation and luciferase reporter assays, we demonstrated that the transcription of porcine ERp44 is repressed through binding of PPARγ to a peroxisome proliferator response element site located between positions −981 and −1004 in its 5′-flanking region. In human embryonic kidney 293 cells stably transfected with cDNA encoding porcine adiponectin, the secretion of adiponectin was significantly up-regulated and the ERp44 mRNA was down-regulated observably, by either the treatment of PPARγ agonist rosiglitazone or the overexpression of PPARγ in these cells. Taken together, our results indicated that PPARγ is an essential regulatory factor for the transcriptional activity of ERp44, which in turn controls the secretion of adiponectin.

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
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