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Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan‐polysaccharide rat model of Crohn's disease

Rahal, Kinan MD1,*; Schmiedlin‐Ren, Phyllissa MD1; Adler, Jeremy MD, MSc2; Dhanani, Muhammad BA1; Sultani, Victoria BA1,*; Rittershaus, Ahren C. MD3; Reingold, Laura1; Zhu, Ji PhD4; McKenna, Barbara J. MD3; Christman, Gregory M. MD5; Zimmermann, Ellen M. MD1,*

doi: 10.1002/ibd.21843
Original Article: Original Basic Science Articles

Background:: Resveratrol has antiinflammatory and antifibrotic effects. Resveratrol decreases proliferation and collagen synthesis by intestinal smooth muscle cells. We hypothesized that resveratrol would decrease inflammation and fibrosis in an animal model of Crohn's disease.

Methods:: Peptidoglycan‐polysaccharide (PG‐PS) or human serum albumin (HSA) was injected into the bowel wall of Lewis rats at laparotomy. Resveratrol or vehicle was administered daily by gavage 1–27 days postinjection. On day 28, gross abdominal and histologic findings were scored. Cecal collagen content was measured by colorimetric analysis of digital images of trichrome‐stained sections. Cecal levels of procollagen, cytokine, and growth factor mRNAs were determined.

Results:: PG‐PS‐injected rats (vehicle‐treated) developed more fibrosis than HSA‐injected rats by all measurements: gross abdominal score (P < 0.001), cecal collagen content (P = 0.04), and procollagen I and III mRNAs (P ≤ 0.0007). PG‐PS‐injected rats treated with 40 mg/kg resveratrol showed a trend toward decreased gross abdominal score, inflammatory cytokine mRNAs, and procollagen mRNAs. PG‐PS‐injected rats treated with 100 mg/kg resveratrol had lower inflammatory cytokine mRNAs (IL‐1β [3.50 ± 1.08 vs. 10.79 ± 1.88, P = 0.005], IL‐6 [17.11 ± 9.22 vs. 45.64 ± 8.83, P = 0.03], tumor necrosis factor alpha (TNF‐α) [0.80 ± 0.14 vs. 1.89 ± 0.22, P = 0.002]), transforming growth factor beta 1 (TGF‐β1) mRNA (2.24 ± 0.37 vs. 4.06 ± 0.58, P = 0.01), and histologic fibrosis score (6.4 ± 1.1 vs. 9.8 ± 1.0; P = 0.035) than those treated with vehicle. There were trends toward decreased gross abdominal score and decreased cecal collagen content. Procollagen I, procollagen III, and IGF‐I mRNAs also trended downward.

Conclusions:: Resveratrol decreases inflammatory cytokines and TGF‐β1 in the PG‐PS model of Crohn's disease and demonstrates a promising trend in decreasing tissue fibrosis. These findings may have therapeutic applications in inflammatory bowel disease. (Inflamm Bowel Dis 2011;)

1Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan

2Department of Pediatrics, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan

3Department of Pathology, University of Michigan, Ann Arbor, Michigan

4Department of Statistics, University of Michigan, Ann Arbor, Michigan

5Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan

Current address for Kinan Rahal: Department of Internal Medicine, Division of Gastroenterology, Texas A&M Health Science Center College of Medicine, Temple, Texas

Current address for Victoria Sultani: Ohio State University College of Medicine, Columbus, Ohio

Reprints: Ellen M. Zimmermann, MD, University of Michigan, Department of Internal Medicine, Division of Gastroenterology, Room 6520 MSRB I/SPC 5682, 1150 W. Medical Center Dr., Ann Arbor, MI 48109

Email: ezimmer@umich.edu

Received 28 June 2011; Accepted 5 July 2011

Published online 29 August 2011 in Wiley Online Library (wileyonlinelibrary.com).

Supported by a grant from the National Institutes of Health (1RO1DK073992 to E.M.Z.).

© Crohn's & Colitis Foundation of America, Inc.
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