Anti-diarrheal activities of phytol along with its possible mechanism of action through in-vivo and in-silico models

Cell Mol Biol (Noisy-le-grand). 2020 Jun 25;66(4):243-249.

Abstract

Phytol (PHY), a chlorophyll-derived diterpenoid, exhibits numerous pharmacological properties, including antioxidant, antimicrobial, and anticancer activities. This study evaluates the anti-diarrheal effect of phytol (PHY) along with its possible mechanism of action through in-vivo and in-silico models. The effect of PHY was investigated on castor oil-induced diarrhea in Swiss mice by using prazosin, propranolol, loperamide, and nifedipine as standards with or without PHY. PHY at 50 mg/kg (p.o.) and all other standards exhibit significant (p < 0.05) anti-diarrheal effect in mice. The effect was prominent in the loperamide and propranolol groups. PHY co-treated with prazosin and propranolol was found to increase in latent periods along with a significant reduction in diarrheal section during the observation period than other individual or combined groups. Furthermore, molecular docking studies also suggested that PHY showed better interactions with the α- and β-adrenergic receptors, especially with α-ADR1a and β-ADR1. In the former case, PHY showed interaction with hydroxyl group of Ser192 at a distance of 2.91Å, while in the latter it showed hydrogen bond interactions with Thr170 and Lys297 with a distance of 2.65 and 2.72Å, respectively. PHY exerted significant anti-diarrheal effect in Swiss mice, possibly through blocking α- and β-adrenergic receptors.

Keywords: Diarrhea; Diterpenoid; Molecular docking.; Mus musculus; Phytol.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Castor Oil
  • Computer Simulation*
  • Diarrhea / drug therapy*
  • Disease Models, Animal
  • Fasting
  • Humans
  • Ion Channels / chemistry
  • Ion Channels / metabolism
  • Male
  • Mice
  • Models, Biological*
  • Molecular Docking Simulation
  • Phytol / pharmacology
  • Phytol / therapeutic use*
  • Receptors, Adrenergic, alpha-1 / chemistry
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Adrenergic, beta / chemistry
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Opioid, mu / chemistry
  • Receptors, Opioid, mu / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Ion Channels
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, beta
  • Receptors, Opioid, mu
  • Phytol
  • Castor Oil