Citrus nutraceutical eriocitrin and its metabolites are partial agonists of peroxisome proliferator�activated receptor gamma (PPARγ): a molecular docking and molecular dynamics study.

Mahesh, G. and Triveni, Pardhi and Jahnavi, Ravilla and Subhash, Chandra and Sridevi Annapurna, Singh (2022) Citrus nutraceutical eriocitrin and its metabolites are partial agonists of peroxisome proliferator�activated receptor gamma (PPARγ): a molecular docking and molecular dynamics study. Journal of Biomolecular Structure and Dynamics.

PDF Journal of Biomolecular Structure and Dynamics 2022-1.pdf - Published Version Restricted to Registered users only Download (4MB) | Request a copy

Abstract

Peroxisome proliferator-activated receptor gamma (PPARc) agonists are potent insulin sensitizers in treat�ing type 2 diabetes. Despite being very effective in the fight against diabetes-mediated complications, PPARc agonists are accompanied by severe side effects leading to complicated health problems, making the discovery of novel safe ligands highly pertinent. A significant intense research effort is in progress to explore the PPARc activating potential of a wide range of natural compounds. Lemon (Citrus limon) con�tains various bioactive flavonoids, and eriocitrin is the major flavonoid. It possesses substantial antioxi�dant and anticancer, lipid-lowering activities and prevents obesity-associated metabolic diseases. Eriocitrin is metabolized to eriodictyol in the intestine, and the absorbed eriodictyol undergoes conver�sion to numerous metabolites in vivo. It is unclear if eriocitrin or its metabolites are responsible for their beneficial effects. We have used molecular docking, ADMET properties, drug-likeness score and molecular dynamics simulation study to find if eriocitrin and its metabolites are potent binders for PPARc. Docking studies revealed that eriocitrin binds to PPARc with the highest binding energy, but ADMET properties and in vivo studies show that the bioavailability of eriocitrin is very poor. Molecular dynamics studies were carried out to validate the docking results, and multiple parameters like RMSD, RMSF, Radius of gyr�ation, SASA, hydrogen bond analysis, interaction energy, principal component analysis, Gibbs free energy and MM-PBSA were calculated. Based on our studies, eriodictyol, eriodictyol 7-O-glucuronide, eriodictyol 30 -O-glucuronide, homoeriodictyol and homoeriodictyol 7-O-glucuronide which are metabolites of erioci�trin appear to be potent partial agonists of PPARc under physiological conditions.

Item Type:	Article
Uncontrolled Keywords:	Eriocitrin; peroxisome proliferator-activated receptor gamma; metabolites; dock�ing; simulation
Subjects:	500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 18 Flavonoid Chemistry 600 Technology > 08 Food technology > 24 Fruits > 03 Citrus fruits
Divisions:	Protein Chemistry and Technology
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	24 May 2023 04:45
Last Modified:	24 May 2023 04:45
URI:	http://ir.cftri.res.in/id/eprint/16444

Actions (login required)

View Item