Inflammatory bowel diseases (IBD) are characterized by proinflammatory
cytokines, tissue damage and loss of neuron in inflamed mucosa, which implies the cholinergic anti-inflammatory pathway may be destroyed during the process of inflammatory response. In the study, we identified the effect of
cholinergic agonist as
anabaseine (AN) and
nicotinic receptor antagonist as
chlorisondamine diiodide (CHD) on trinitrobenzene
sulfonic acid (TNBS)-induced
colitis, to investigate the potential
therapeutic effect of the cholinergic anti-inflammatory pathway on IBD. Experimental
colitis was induced by TNBS at day 1, 10 mug AN or 1.5 mug CHD was injected i.p. to mouse right after the induction of
colitis, and repeated on interval day till the mice were sacrificed at day 8. Colonic
inflammation was examined by histological analysis,
myeloperoxidase (MPO) activity, and the production of tumour
necrosis factor (
TNF)-alpha in tissue. Lamina propria mononuclear cells (LPMC) were isolated, and
NF-kappaB activation was detected by western blot. The mice with
colitis treated by AN showed less tissue damage, less MPO activity, less
TNF-alpha production in colon, and inhibited
NF-kappaB activation in LPMC, compared with those mice with
colitis untreated, whereas the mice with
colitis treated by CHD showed the worst tissue damage, the highest MPO activity, the highest
TNF-alpha level, and enlarged
NF-kappaB activation in LPMC. Agonist of the cholinergic anti-inflammatory pathway inhibits colonic inflammatory response by downregulating the production of
TNF-alpha, and inhibiting
NF-kappaB activation, which suggests that modulating the cholinergic anti-inflammatory pathway may be a new potential management for IBD.