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Pharmacol Res. 2015 Oct;100:271-80. doi: 10.1016/j.phrs.2015.08.012. Epub 2015 Aug 20.

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

Author information

1
Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Ratchathewee, Bangkok, Thailand.
2
Department of Chemistry, Faculty of Science and Technology, Suan Sunandha Rajabhat University, Dusit, Bangkok, Thailand.
3
Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Ratchathewee, Bangkok, Thailand; Excellent Center for Drug Discovery, Thailand Center of Excellence for Life Sciences (TCELS), Bangkok, Thailand.
4
Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Ratchathewee, Bangkok, Thailand; Excellent Center for Drug Discovery, Thailand Center of Excellence for Life Sciences (TCELS), Bangkok, Thailand; Center of Excellence on Environmental Health and Toxicology, Ministry of Education, Bangkok, Thailand. Electronic address: chatchai.mua@mahidol.ac.th.

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 Ca2+-activated Cl- channels (CaCC) without affecting intracellular Ca2+ concentrations or Ca2+-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-.

KEYWORDS:

Black pepper; CFTR; Cholera; Diarrhea; Piperine

PMID:
26297981
DOI:
10.1016/j.phrs.2015.08.012
[Indexed for MEDLINE]

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