The antidiarrheal and spasmolytic activities of Phyllanthus emblica are mediated through dual blockade of muscarinic receptors and Ca2+ channels

Aim of the study: This study was aimed at providing the possible mechanisms for the medicinal use of Phyllanthus emblica in diarrhea. Materials and methods: The in vivo studies were conducted in mice, while isolated rabbit jejunum and guinea-pig ileum were used for the in vitro experiments. Results: The crude extract of Phyllanthus emblica (Pe.Cr), which tested positive for alkaloids, tannins, terpenes, flavonoids, sterols and coumarins, caused inhibition of castor oil-induced diarrhea and intestinal fluid accumulation in mice at 500-700 mg/kg. In isolated rabbit jejunum, Pe.Cr relaxed carbachol (CCh) and K+ (80 mM)-induced contractions, in a pattern similar to that of dicyclomine. The preincubation of guinea pig-ileum with Pe.Cr (0.3 mg/mL), caused a rightward parallel shift in the concentration-response curves (CRCs) of acetylcholine without suppression of the maximum response. While at the next higher concentration (1 mg/mL), it produced a non-parallel rightward shift with suppression of the maximum response, similar to that of dicyclomine, suggesting anticholinergic and Ca2+ channel blocking (CCB)-like antispasmodic effect. The CCB-like activity was further confirmed when pretreatment of the tissue with Pe.Cr, shifted the CRCs of Ca2+ to the right with suppression of the maximum response, similar to nifedipine or dicyclomine. The activity-directed fractions of Pe.Cr showed a combination of Ca2+ antagonist and anticholinergic like components in all fractions but with varying potency. Conclusion: These results indicate that the Phyllanthus emblica fruit extract possesses antidiarrheal and spasmolytic activities, mediated possibly through dual blockade of muscarinic receptors and Ca2+ channels, thus explaining its medicinal use in diarrhea. (C) 2010 Elsevier Ireland Ltd. All rights reserved.