Antidiarrheal activity of farnesol in rodents: Pharmacological actions and molecular docking

Eur J Pharmacol. 2020 May 5:874:172986. doi: 10.1016/j.ejphar.2020.172986. Epub 2020 Feb 4.

Abstract

Diarrhea is a condition in which the individual has about three or more daily bowel movements, followed by changes in stool consistency. It is currently considered as one of the worst public health problems due to the number of cases and deaths involved and difficulty of treatment. Thus, the use of natural products is an alternative for new treatments. Among these possibilities is Farnesol (C15H26O), a sesquiterpene found in different herbal species that has known biological activities. The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE2. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests with castor oil and PGE2, being considered as the standard dose, reducing motility by anticholinergic mechanisms. There was a reduction in fluid secretion when FOH interacted directly with GM1 receptors; cholera toxin and molecular docking showed strong interaction between farnesol and these targets. In view of the results presented, the antidiarrheal activity occurs through anticholinergic, anti-inflammatory and anti-secretory action, making farnesol a potential candidate for the development of a new drug to treat diarrheal diseases.

Keywords: Castor oil; Cholera; Farnesol; Gastrointestinal transit; Sesquiterpene.

MeSH terms

  • Animals
  • Antidiarrheals / pharmacology*
  • Antidiarrheals / therapeutic use*
  • Castor Oil
  • Chlorides / metabolism
  • Cholera Toxin
  • Diarrhea / chemically induced
  • Diarrhea / drug therapy*
  • Diarrhea / metabolism*
  • Dinoprostone
  • Farnesol / pharmacology*
  • Farnesol / therapeutic use*
  • Female
  • Gastrointestinal Motility / drug effects
  • Intestinal Absorption / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Secretions / metabolism
  • Male
  • Mice
  • Molecular Docking Simulation
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Receptors, Cell Surface / metabolism

Substances

  • Antidiarrheals
  • Chlorides
  • Narcotic Antagonists
  • Receptors, Cell Surface
  • ganglioside receptor
  • Naloxone
  • Farnesol
  • Castor Oil
  • Cholera Toxin
  • Dinoprostone