Cannabidiol Reduces Intestinal Inflammation through the Control of Neuroimmune Axis
Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release
neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response,
representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD) is an
interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic
effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with
ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly
counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B.
Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a
considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the
treatment of LPS-mice with CBD reduced TNF-a expression and the presence of cleaved caspase-3. Similar results were
obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation
and in remission stimulated with LPS+INF-c, an increased glial cell activation and intestinal damage were evidenced. CBD
reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic
mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric
reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived
from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our
results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.
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