Cellular Mechanisms Underlying the Laxative Effect of Flavonol Naringenin on Rat Constipation ModelReport as inadecuate




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Background and 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 µM elicited a concentration-dependent and sustained increase in the short-circuit current ISC, which could be inhibited in Cl− free solution or by bumetanide and DPC diphenylamine-2-carboxylic acid, but not by DIDS 4, 4′- diisothiocyanatostilbene-2, 2′-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 Cl− 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 Cl− 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 Cl− 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.



Author: Zi-Huan Yang , Hai-Jie Yu , Ao Pan, Jian-Yang Du, Ye-Chun Ruan, Wing-Hung Ko, Hsiao-Chang Chan , Wen-Liang Zhou

Source: http://plos.srce.hr/



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