Inhibition of intestinal chloride secretion by piperine as a cellular basis for the anti-secretory effect of black peppers. (October 2015)

• Record Type: Journal Article
• Authors: Pongkorpsakol, Pawin; Wongkrasant, Preedajit; Kumpun, Saowanee; Chatsudthipong, Varanuj; Muanprasat, Chatchai
• Is Part Of: Pharmacological research. Volume 100(2015:Oct.)
• Page Start: 271
• Page End: 280
• Publication Date: 2015-10
• Subjects: Diarrhea -- Black pepper -- Piperine -- CFTR -- Cholera; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2015.08.012
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: 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 − 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 − secretion. Notably, piperine inhibited CFTR Cl − channel activity (IC50 #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 + channels, but it had no effect on Na + –K + –Cl − cotransporters or Na + –K + ATPases. Piperine suppressed Ca 2+ -activated Cl − channels (CaCC) without affecting intracellular Ca 2+ concentrations or Ca 2+ -activated basolateral K + channels. Collectively, this study indicates that the anti-secretory effect of piperine involves the inhibition of CFTR, CaCC and cAMP-activated basolateral K + channels. Piperine represents a novel class of drug candidates for the treatment of diarrheal diseases caused by the intestinal hypersecretion of Cl − .