Study the Activity of Natural Ligands of Lettuce as Agonists in the Management of Uremic Pruritus: An In-Silico Simulation Survey

Abstract Uremic pruritus frequently occurs in patients on dialysis for more than three months. It is one of the most prominent, debilitating, and distressing symptoms in these patients, and despite various studies, no definite treatment has been found. The purpose of this research is to investigate the outstanding potential of natural components of lettuce (Lactuca Sativa L.) in the management of pruritus. ADME analysis and PASS predictions were employed to determine the drug likeliness potential of these natural ligands. A molecular docking study was performed on 19 bioactive ligands of lettuce against four protein receptors. The results showed that most of the selected compounds strongly react with kappa-opioid receptors 4DJH, 6VI4, 6B73, and G protein-coupled receptor 5ZTY and have better binding energies compared to the antipruritic drug gabapentin. The obtained docking scores (DS) and inhibition constants (Ki) revealed that the most potent antipruritic activities are exhibited by campesterol, δ-tocopherol, α-tocopherol, Δ-tocopherol, and α-lactucerol ligands. Our results from the MD simulation of the campesterol-5ZTY complex provide a theoretical validation that the ligand is stabilized in the protein active site. The binding free energy calculations quantitatively show that the association of the ligand to the protein increases the change in the total binding energy. This in-silico approach proposes that the natural ligands of lettuce could exert antipruritic effects by activating kappa-opioid receptors and may become recommended over synthetic drugs.