title: Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan-polysaccharide rat model of Crohn's disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Kinan
authors.initials: K
authors.lastname: Rahal
authors.forename: Phyllissa
authors.initials: P
authors.lastname: Schmiedlin-Ren
authors.forename: Jeremy
authors.initials: J
authors.lastname: Adler
authors.forename: Muhammad
authors.initials: M
authors.lastname: Dhanani
authors.forename: Victoria
authors.initials: V
authors.lastname: Sultani
authors.forename: Ahren C
authors.initials: AC
authors.lastname: Rittershaus
authors.forename: Laura
authors.initials: L
authors.lastname: Reingold
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: McKenna
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Christman
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Zimmermann
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003424:Crohn Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D007082:Ileum / Q000187:drug effects / Q000473:pathology; D010457:Peptidoglycan / Q000009:adverse effects; D011134:Polysaccharides / Q000009:adverse effects; D011347:Procollagen / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D000077185:Resveratrol; D012709:Serum Albumin / Q000009:adverse effects; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D010457:Peptidoglycan; D011134:Polysaccharides; D011347:Procollagen; D012709:Serum Albumin; D013267:Stilbenes; D000077185:Resveratrol