Molecular Docking Guided Screening of Phytoconstituents from Artemisia iwayomogi as Potential PPARδ Agonists

Abstract

Metabolic syndrome is a disease condition characterized by decreased insulin sensitivity, hyperlipidemia, abdominal obesity, hypertension, and myocardial diseases, primarily related to a high-fat diet and lack of physical exercise. Peroxisome proliferator-activated receptor (PPAR) δ stimulation changes the body’s energy fuel preference to fats from sugar. PPARδ is expressed universally in all tissues of the human body, particularly those involving lipid metabolism. PPARδ is an evolving pharmacological target for the pharmacotherapeutics of diseases linked to metabolic syndrome. Artemisia iwayomogi ethanol extract was reported as PPARδ agonist and reduced diet-induced overweight via stimulation of fatty acid oxidation in the skeletal muscles. The present study is designed to evaluate in silico some phytoconstituents, including 4 coumarins, 12 flavonoids, 5 phenolic compounds and 7 caffeoyl-quinic acid derivatives found in A. iwayomogi to explore their binding mode and interactions with the PPARδ protein. A total of 28 compounds evaluated in silico, 16 compounds displayed good binding free energy, and significant docking interactions with the binding site residues of PPARδ protein supporting the in vitro PPARδ agonistic activity of A. iwayomogi extract. Amongst these, scopolin, patuletin, patuletin-3-glucoside, 1,2-bis(4-hydroxy-3-methoxyphenyl)prop-1,3-diol, 3-caffeoylquinic acid, and 1,3-dicaffeoylquinic acid displayed most significant binding interactions with binding site residues of PPARδ. This information can be utilized for developing potent and non-toxic natural PPARδ agonists for the management of disorders related to metabolic syndrome.