title: Abnormal cannabidiol attenuates experimental colitis in mice, promotes wound healing and inhibits neutrophil recruitment.
abstract: BACKGROUND
  Non-psychotropic atypical cannabinoids have therapeutic potential in a variety of inflammatory conditions including those of the gastrointestinal tract. Here we examined the effects of the atypical cannabinoid abnormal cannabidiol (Abn-CBD) on wound healing, inflammatory cell recruitment and colitis in mice.
  
  
  METHODS
  Colitis was induced in CD1 mice by a single intrarectal administration of trinitrobenzene sulfonic acid (TNBS, 4 mg/100 μl in 30 % ethanol) and Abn-CBD and/or the antagonists O-1918 (Abd-CBD), AM251 (CB1 receptor) and AM630 (CB2 receptor), were administered intraperitoneally (all 5 mg/kg, twice daily for 3 days). The degree of colitis was assessed macro- and microscopically and tissue myeloperoxidase activity was determined. The effects of Abn-CBD on wound healing of endothelial and epithelial cells (LoVo) were assessed in a scratch injury assay. Human neutrophils were employed in Transwell assays or perfused over human umbilical vein endothelial cells (HUVEC) to study the effect of Abn-CBD on neutrophil accumulation and transmigration.
  
  
  RESULTS
  TNBS-induced colitis was attenuated by treatment with Abn-CBD. Histological, macroscopic colitis scores and tissue myeloperoxidase activity were significantly reduced. These effects were inhibited by O-1918, but not by AM630, and only in part by AM251. Wound healing of both HUVEC and LoVo cells was enhanced by Abn-CBD. Abn-CBD inhibited neutrophil migration towards IL-8, and dose-dependently inhibited accumulation of neutrophils on HUVEC.
  
  
  CONCLUSIONS
  Abn-CBD is protective against TNBS-induced colitis, promotes wound healing of endothelial and epithelial cells and inhibits neutrophil accumulation on HUVEC monolayers. Thus, the atypical cannabinoid Abn-CBD represents a novel potential therapeutic in the treatment of intestinal inflammatory diseases.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB Canada ; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB Canada.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Krohn
authors.affiliation: Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB Canada ; Department of Physiology and Pharmacology, University of Calgary, Calgary, AB Canada.
authors.forename: Sean A
authors.initials: SA
authors.lastname: Parsons
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB Canada ; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB Canada ; Department of Biochemistry, Medial University of Lodz, Lodz, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
authors.affiliation: Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB Canada ; Department of Physiology and Pharmacology, University of Calgary, Calgary, AB Canada.
authors.forename: Kamala D
authors.initials: KD
authors.lastname: Patel
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB Canada ; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB Canada.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Yates
authors.affiliation: Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB Canada ; Department of Physiology and Pharmacology, University of Calgary, Calgary, AB Canada ; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB Canada.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Sharkey
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB Canada ; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB Canada ; Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Storr
keywords: Abnormal cannabidiol; Cannabinoids; Neutrophil recruitment; O-1918; TNBS-colitis; Wound healing