Anti-diarrheal activity of (-)-epicatechin from Chiranthodendron pentadactylon Larreat: experimental and computational studies.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND 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. CONCLUSION: 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.

Antisecretory activity from the flowers of Chiranthodendron pentadactylon and its flavonoids on intestinal fluid accumulation induced by Vibrio cholerae toxin in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The flowers of Chiranthodendron pentadactylon Larreat. (Sterculiaceae) has been traditionally used as folk medicine in Mexico for the treatment of gastrointestinal disorders such as diarrhea and dysentery. AIM OF THE STUDY: This study aimed to assess the antisecretory activity which supports the therapeutic use of Chiranthodendron pentadactylon and its flavonoids to treat diarrhea. MATERIALS AND METHODS: The methanol extract of Chiranthodendron pentadactylon, subsequent fractions, and flavonoids were evaluated on cholera toxin-induced intestinal secretion in rat jejunal loops model. RESULTS: Three antisecretory flavonoids were isolated by bioassay-guided purification, namely, isoquercitrin 3, (+)-catechin 4 and (-)-epicatechin 5. Among them, epicatechin exhibited the most potent antisecretory activity with ID(50) of 8.3 microM/kg. Its potency was close that of to loperamide (ID(50) 6.1 microM/kg), drug used as control. Isoquercitrin (ID(50) 19.2 microM/kg) and catechin (ID(50) 51.7 microM/kg) showed moderate and weak activity, respectively. CONCLUSION: The results of the present study lend some support to the anecdotal report for the traditional use of the flowers of Chiranthodendron pentadactylon in the control of dysentery.