title: The antidiarrheal and spasmolytic activities of Phyllanthus emblica are mediated through dual blockade of muscarinic receptors and Ca2+ channels.
abstract: OBJECTIVE
  This study was aimed at providing the possible mechanisms for the medicinal use of Phyllanthus emblica in diarrhea.
  
  
  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 Ca(2+) 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 Ca(2+) 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 Ca(2+) antagonist and anticholinergic like components in all fractions but with varying potency.
  
  
  CONCLUSIONS
  These results indicate that the Phyllanthus emblica fruit extract possesses antidiarrheal and spasmolytic activities, mediated possibly through dual blockade of muscarinic receptors and Ca(2+) channels, thus explaining its medicinal use in diarrhea.
authors.affiliation: Natural Product Research Division, Department of Biological and Biomedical Sciences, Aga Khan University Medical College, Karachi 74800, Pakistan.
authors.forename: Malik Hassan
authors.initials: MH
authors.lastname: Mehmood
authors.forename: Hasan Salman
authors.initials: HS
authors.lastname: Siddiqi
authors.forename: Anwarul Hassan
authors.initials: AH
authors.lastname: Gilani
mesh_terms: D000818:Animals; D000930:Antidiarrheals / Q000302:isolation & purification / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology; D003967:Diarrhea / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D020834:Ethnopharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D018727:Muscarinic Antagonists / Q000302:isolation & purification / Q000494:pharmacology; D010154:Pakistan; D010276:Parasympatholytics / Q000302:isolation & purification / Q000494:pharmacology*; D029842:Phyllanthus emblica / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D011817:Rabbits
chemical_list: D000930:Antidiarrheals; D002121:Calcium Channel Blockers; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010936:Plant Extracts