Abnormal cannabidiol attenuates experimental colitis in mice, promotes wound healing and inhibits neutrophil recruitment
BackgroundNon 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.MethodsColitis was induced in CD1 mice by a single intrarectal administration of trinitrobenzene sulfonic acid (TNBS, 4 mg/100 ml 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.ResultsTNBS 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.ConclusionsAbn 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.
Journal of Inflammation