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|Title:||Inhibition of intestinal chloride secretion by piperine as a cellular basis for the anti-secretory effect of black peppers|
Suan Sunandha Rajabhat University
Thailand Ministry of Education
|Citation:||Pharmacological Research. Vol.100, (2015), 271-280|
|Abstract:||© 2015 Elsevier Ltd. All rights reserved. Piperine is the principal alkaloid in black peppers (Piper nigrum L.), which is a commonly included spice in anti-diarrheal formulations. Piperine has antispasmodic activities, but its anti-secretory effect is not known. Therefore, this study investigated the anti-secretory effect of piperine and its underlying mechanism. Piperine inhibited cAMP-mediated Cl<sup>-</sup> secretion in human intestinal epithelial (T84) cells, similar to black pepper extract. Intraluminal administration of piperine (2 μg/loop) suppressed cholera toxin-induced intestinal fluid accumulation by ∼85% in mice. The anti-secretory mechanism of piperine was investigated by evaluating its effects on the activity of transport proteins involved in cAMP-mediated Cl<sup>-</sup> secretion. Notably, piperine inhibited CFTR Cl<sup>-</sup> channel activity (IC<inf>50</inf>#8'6#10 μM) without affecting intracellular cAMP levels. The mechanisms of piperine-induced CFTR inhibition did not involve MRP4-mediated cAMP efflux, AMPK or TRPV1. Piperine also inhibited cAMP-activated basolateral K<sup>+</sup> channels, but it had no effect on Na<sup>+</sup>-K<sup>+</sup>-Cl<sup>-</sup> cotransporters or Na<sup>+</sup>-K<sup>+</sup> ATPases. Piperine suppressed Ca<sup>2+</sup>-activated Cl<sup>-</sup> channels (CaCC) without affecting intracellular Ca<sup>2+</sup> concentrations or Ca<sup>2+</sup>-activated basolateral K<sup>+</sup> channels. Collectively, this study indicates that the anti-secretory effect of piperine involves the inhibition of CFTR, CaCC and cAMP-activated basolateral K<sup>+</sup> channels. Piperine represents a novel class of drug candidates for the treatment of diarrheal diseases caused by the intestinal hypersecretion of Cl<sup>-</sup>.|
|Appears in Collections:||Scopus 2011-2015|
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