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【原文题目】:Cellular Mechanisms Underlying the Laxative Effect of Flavonol Naringenin on Rat Constipation Model

【作者】:Zi-Huan Yang1., Hai-Jie Yu1., Ao Pan1, Jian-Yang Du1, Ye-Chun Ruan1, Wing-Hung Ko2, Hsiao-Chang Chan2*, Wen-Liang Zhou1*
1 The School of Life Science, Sun Yat-sen University, Guangzhou, China, 2 Faculty of Medicine, Department of Physiology, Chinese University of Hong Kong, Shatin, Hong Kong


Background & Aims: Symptoms of constipation are extremely common, especially in the elderly. The present study aim to identify an efficacious treatment strategy for constipation by evaluating the secretion-promoting and laxative effect of a herbal compound, naringenin, on intestinal epithelial anion secretion and a rat constipation model, respectively.

Methods/Principal Findings: In isolated rat colonic crypts, mucosal addition of naringenin (100 mM) elicited a concentration-dependent and sustained increase in the short-circuit current (ISC), which could be inhibited in Cl2 free solution or by bumetanide and DPC (diphenylamine-2-carboxylic acid), but not by DIDS (4, 49- diisothiocyanatostilbene-2, 29-disulfonic acid). Naringenin could increase intracellular cAMP content and PKA activity, consisted with that MDL-12330A
(N-(Cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride) pretreatment reduced the naringenin-induced ISC. In addition, significant inhibition of the naringenin-induced ISC by quinidine indicated that basolateral K+ channels were involved in maintaining this cAMP-dependent Cl2 secretion. Naringenin-evoked whole cell current which exhibited a linear
I–V relationship and time-and voltage- independent characteristics was inhibited by DPC, indicating that the cAMP activated Cl2 conductance most likely CFTR (cystic fibrosis transmembrane conductance regulator) was involved. In rat constipation model, administration of naringenin restored the level of fecal output, water content and mucus secretion compared to
loperamide-administrated group.

Conclusions: Taken together, our data suggest that naringenin could stimulate Cl2 secretion in colonic epithelium via a signaling pathway involving cAMP and PKA, hence provide an osmotic force for subsequent colonic fluid secretion by which the laxative effect observed in the rat constipation model. Naringenin appears to be a novel alternative treatment strategy for constipation.


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