Abstract
Objective: The objective of the study was to investigate the effect of aqueous extract of unpolished dark purple glutinous Thai rice variety Luem Pua(LP) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in rat and the possible cholinomimetic effects of the extract.Methods: The effect of LP extract (0.5, 1, or 1.5 mg/ml final concentration) on ileum contraction was tested using isolated guinea pig ileum. Certainagonists (acetylcholine, tetramethylammonium, and clonidine) and antagonists (hexamethonium chloride and atropine) were studied to determinethe cholinomimetic effect of the extract. The effects of LP extract (5 g/kg/day) in DSS-induced UC model (drinking water was replaced with 3%DSS in water for 7 days) in rat were evaluated. On each day of treatment, the change of disease activity index (DAI) was recorded. At the end of theexperiments, rats were terminated and disease severity expressed as DAI, colon length, and spleen weight were determined.Results: LP extract at the concentration of 0.5, 1, and 1.5 mg/ml (final concentration) could contract the ileum in a dose-dependent manner and beblocked completely by atropine. Oral administration of LP extract could significantly attenuate the severity of DSS-induced UC as seen by the reductionof DAI, colon length, and spleen weight.Conclusion: Results in isolated guinea pig ileum suggest that LP might contain active substance that could activate muscarinic receptors. In additionto antioxidant activity, through activation of muscarinic receptor, might explain the protective effects of LP extract against DSS-induced UC in rats.
Highlights
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive tract and the two main subtypes of IBD are Crohn’s disease (CD) and ulcerative colitis (UC)
The contraction induced by TMA was clearly seen and preincubation with C6 resulted in a significant decrease of TMA response
ACh and muscarinic receptor antagonist The ileum contraction induced by 3 μg/ml of ACh was completely inhibited by 2 μg/ml of atropine, a muscarinic receptor antagonist
Summary
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive tract and the two main subtypes of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). Increasing of pro-inflammatory cytokines can be inhibited by activation of cholinergic receptors on intestinal mucosal epithelial cells and could attenuate cytokine activities in dextran sulfate sodium (DSS)-induced colitis [3]. Under inflammatory conditions, activation of the cholinergic anti-inflammatory pathway through muscarinic receptors on epithelial cells is suggested to help maintain epithelial barrier function and protects against cytokine-induced barrier dysfunction [5]. Increasing intestinal cholinergic anti-inflammatory pathway can alleviate the inflammation and has been identified as one of a potential target for IBD drug [6]. As LP extract could alleviate the memory impairment effect of a muscarinic antagonist, it might be the case that, in addition to anti-oxidant effect, LP might have cholinomimetic activity. The purpose of this study was to investigate the possible cholinomimetic effects of the LP extract in isolated Guinea pig ileum and the effects of the extract in DSS-induced UC in rat model
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