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

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.

• Authors: Muhammad Torequl Islam, Mohammad Asikur Rahman, Maria Saeed, Zaheer Ul-Haq, Md Jahir Alam, Milon Mondal, Rajib Hossain, Mohammad S Mubarak, Bahare Salehi, William N Setzer, Ahmad Faizal Abdull Razis, Javad Sharifi-Rad
• Journal: Cellular and molecular biology (Noisy-le-Grand, France) (Cell Mol Biol (Noisy-le-grand)) Vol. 66 Issue 4 Pg. 243-249 (Jun 25 2020) ISSN: 1165-158X [Electronic] France
• PMID: 32583783 (Publication Type: Journal Article)

Chemical References

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

Topics

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