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

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

Antispasmodic, bronchodilator and vasodilator activities of (+)-catechin, a naturally occurring flavonoid

Catechin is a well-known flavonoid found in many food plants and often utilized by naturopaths for the symptomatic treatment of several gastrointestinal, respiratory and vascular diseases. Our aim was to explore the biological basis for the medicinal use of this flavonoid by investigating whether catechin exhibits any pharmacological activity on smooth muscle preparations. We found that catechin dose-dependently relaxes both spontaneous and high K(+) (80 mM)-induced contraction in rabbit jejunum, showing specificity for the latter by causing a right-ward shift in the Ca(2+) dose-response curve. Similar results were observed with verapamil, a standard Ca(2+) channel blocker (CCB). Catechin also inhibited high K(+)-induced contraction in intact smooth muscle preparations from rat stomach fundus, guinea-pig ileum and guinea-pig trachea. In rat aorta, catechin inhibited phenylephrine (PE, 1 microM) and K(+)-induced contractions in a similar fashion. In PE-contracted, endothelium-intact aorta, this vasodilator effect was partially blocked by Nomega-nitro-L-arginine methyl ester and atropine, indicating activity at cholinergic receptors and possibly a CCB effect at higher doses of catechin. In guinea-pig atria catechin was found inactive. These data suggest that catechin may possess Ca(2+) antagonist activity--in addition to an endothelium-dependent relaxant component in blood vessels--thus providing a pharmacological basis for the efficacy of catechin in hyperexcitability disorders of gastrointestinal, respiratory and vascular smooth muscle