De Filippis D, Esposito G, Cirillo C, Cipriano M, De Winter BY, Scuderi C, Sarnelli G, Cuomo R, Steardo L, De Man JG, Iuvone T.
Enteric glial cells (EGC) actively mediate acute and chronic inflammationin 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-α
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-γ, 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.