title: Anti-diarrheal activity of (-)-epicatechin from Chiranthodendron pentadactylon Larreat: experimental and computational studies.
abstract: BACKGROUND
  Chiranthodendron pentadactylon Larreat is frequently used in Mexican traditional medicine as well as in Guatemalan for several medicinal purposes, including their use in the control of diarrhea.
  
  
  OBJECTIVE
  This work was undertaken to obtain additional information that support the traditional use of Chiranthodendron pentadactylon Larreat, on pharmacological basis using the major antisecretory isolated compound from computational, in vitro and in vivo experiments.
  
  
  METHODS
  (-)-Epicatechin was isolated from ethyl acetate fraction of the plant crude extract. In vivo toxin (Vibrio cholera or Escherichia coli)-induced intestinal secretion in rat jejunal loops models and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on Vibrio cholera toxin were used in experimental studies while the molecular docking technique was used to conduct computational study.
  
  
  RESULTS
  The antisecretory activity of epicatechin was tested against Vibrio cholera and Escherichia coli toxins at oral dose 10 mg/kg in the rat model. It exhibited the most potent activity on Vibrio cholera toxin (56.9% of inhibition). In the case of Escherichia coli toxin its effect was moderate (24.1% of inhibition). SDS-PAGE analysis revealed that both (-)-epicatechin and Chiranthodendron pentadactylon extract interacted with the Vibrio cholera toxin at concentration from 80 μg/mL and 300 μg/mL, respectively. Computational molecular docking showed that epicatechin interacted with four amino acid residues (Asn 103, Phe 31, Phe 223 and The 78) in the catalytic site of Vibrio cholera toxin, revealing its potential binding mode at molecular level.
  
  
  CONCLUSIONS
  The results derived from computational, in vitro and in vivo experiments on Vibrio cholera and Escherichia coli toxins confirm the potential of epicatechin as a new antisecretory compound and give additional scientific support to anecdotal use of Chiranthodendron pentadactylon Larreat in Mexican traditional medicine to treat gastrointestinal disorders such as diarrhea.
authors.affiliation: Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Km. 4.5 Carretera Pachuca-Tulancingo, Unidad Universitaria, CP 42076 Pachuca, Hidalgo, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Velázquez
authors.forename: José
authors.initials: J
authors.lastname: Correa-Basurto
authors.forename: Normand
authors.initials: N
authors.lastname: Garcia-Hernandez
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barbosa
authors.forename: Emiliano
authors.initials: E
authors.lastname: Tesoro-Cruz
authors.forename: Samuel
authors.initials: S
authors.lastname: Calzada
authors.forename: Fernando
authors.initials: F
authors.lastname: Calzada
mesh_terms: D000818:Animals; D000930:Antidiarrheals / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D003967:Diarrhea / Q000188:drug therapy*; D004768:Enterotoxins / Q000008:administration & dosage; D035264:Flowers; D007583:Jejunum / Q000378:metabolism; D008297:Male; D019660:Malvaceae; D008519:Medicine, Traditional; D000432:Methanol / Q000737:chemistry; D008800:Mexico; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000737:chemistry
chemical_list: D000930:Antidiarrheals; D004768:Enterotoxins; D010936:Plant Extracts; D012997:Solvents; D002392:Catechin; D000432:Methanol