title: Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people in industrialized countries. Anecdotal and scientific evidence suggests that Cannabis use may have a positive impact in IBD patients. Here, we investigated the effect of cannabigerol (CBG), a non-psychotropic Cannabis-derived cannabinoid, in a murine model of colitis. Colitis was induced in mice by intracolonic administration of dinitrobenzene sulphonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters (colon weight/colon length ratio and myeloperoxidase activity), by histological analysis and immunohistochemistry; interleukin-1β, interleukin-10 and interferon-γ levels by ELISA, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by western blot and RT-PCR; CuZn-superoxide dismutase (SOD) activity by a colorimetric assay. Murine macrophages and intestinal epithelial cells were used to evaluate the effect of CBG on nitric oxide production and oxidative stress, respectively. CBG reduced colon weight/colon length ratio, myeloperoxidase activity, and iNOS expression, increased SOD activity and normalized interleukin-1β, interleukin-10 and interferon-γ changes associated to DNBS administration. In macrophages, CBG reduced nitric oxide production and iNOS protein (but not mRNA) expression. Rimonabant (a CB1 receptor antagonist) did not change the effect of CBG on nitric oxide production, while SR144528 (a CB2 receptor antagonist) further increased the inhibitory effect of CBG on nitric oxide production. In conclusion, CBG attenuated murine colitis, reduced nitric oxide production in macrophages (effect being modulated by the CB2 receptor) and reduced ROS formation in intestinal epithelial cells. CBG could be considered for clinical experimentation in IBD patients.
authors: Department of Pharmacy, University of Naples Federico II, via D Montesano 49, 80131 Naples, Italy. franborr@unina.it
authors: Francesca
authors: F
authors: Borrelli
authors: Ines
authors: I
authors: Fasolino
authors: Barbara
authors: B
authors: Romano
authors: Raffaele
authors: R
authors: Capasso
authors: Francesco
authors: F
authors: Maiello
authors: Diana
authors: D
authors: Coppola
authors: Pierangelo
authors: P
authors: Orlando
authors: Giovanni
authors: G
authors: Battista
authors: Ester
authors: E
authors: Pagano
authors: Vincenzo
authors: V
authors: Di Marzo
authors: Angelo A
authors: AA
authors: Izzo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D003092:Colitis / Q000188:drug therapy / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002186:Cannabinoids; D053583:Interleukin-1beta; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D017382:Reactive Oxygen Species; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D016753:Interleukin-10; D007371:Interferon-gamma; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; C037036:cannabigerol