Insight into the possible mechanism of antidiarrheal and antispasmodic activities of piperine

Document Type



Biological and Biomedical Sciences


Piperine is a piperidine-ring containing alkaloid and a major constituent of Piper nigrum Linn. and Piper longum Linn. species, belonging to the Piperaceae family. The present study explored their mode of action in gastrointestinal disorders, such as diarrhea and colic. Piperine at the dose of 10 mg/kg provided complete protection from castor oil-induced diarrhea in mice, similar to that of loperamide. In isolated rabbit jejunum preparations, piperine exhibited concentration-dependent inhibition of spontaneous contractions with an EC50 value of 149.1 μM (89.26–249.20, 95% CI). When used to treat high K+ (80 mM)-induced sustained contractions, piperine inhibited such contractions with an EC50 value of 80.86 μM (56.10–116.50, 95% CI), which suggested a calcium channel blocking (CCB) effect. The CCB effect was further confirmed when pretreatment of the tissues with piperine (10–100 μM) caused a rightward shift in the Ca++ concentration–response curves (CRCs) in Ca++-free medium, similar to that caused by verapamil. Loperamide also caused the inhibition of spontaneous and high K+-induced contractions as well as shifted the Ca++ CRCs to the right at concentrations of 1–10 μM. These data indicate that piperine exhibits antidiarrheal and antispasmodic activities, mediated possibly through calcium channel blockade.


Pharmaceutical Biology