Abstract
Purpose: To use in silico docking analysis and ADMET prediction of silibinin and glycyrrhetic acid to determine their pharmacokinetic and pharmacodynamic properties as therapeutic molecules against inflammatory disorders. Methods: The study utilized plant-derived compounds with known anti-inflammatory activity. Three important enzymes, including COX-2, 5β-reductase and phospholipase A2, that are involved in the mediation of inflammatory processes, were chosen as protein targets for the ligands (silibinin and glycyrrhetic acid). Q-Site Finder and admetSAR were employed for active site prediction and ADMET profile, respectively. Furthermore, protein-ligand complexes were visually inspected by LigPlot and Chimera. Results: Post-docking analysis confirmed strong interaction of silibinin and glycyrrhetic acid with their respective targets. ADMET profiles for both compounds were very promising. Both ligands (silibinin and glycyrrhetic acid) showed strong binding energy for all three target proteins (-7.5 to -10.9 kcal/mol). Moreover, Asp347, Gln350, Gly354, Gln192, His351, Ser579 and Phe580 were the common interacting residues in the target proteins for both ligands. Conclusion: Glycyrrhetic acid possesses superior ADMET profile to silibinin. Hydrophobic interactions between the two ligands (glycyrrhetinic acid and silibinin) and the three target proteins (COX-2, phospholipase A2 and 5β-reductase) are significant. Keywords: Silibinin, Glycyrrhetic acid, ADMET, Docking studies, Phospholipase A2, COX-2, 5β-Reductase
Highlights
Xenobiotics and toxins injure the liver and can result in substantial hepatic pathology
Hepatocytes are responsible for the excretion of drugs from animals [1]
Phytochemicals like silymarin and glycyrrhizin in suitable combinations are used as drugs for patients with liver disorders as they possess hepatoprotective property against inflammation [11,17]
Summary
Xenobiotics and toxins injure the liver and can result in substantial hepatic pathology. The liver metabolizes and excretes drugs and xenobiotics. Toxins, chemotherapeutic agents like acetamide, and a hepatotoxic agent, carbon tetrachloride (CCl4) can damage hepatocytes and lead to liver inflammation (hepatitis) and cirrhosis [2]. Plants and their extracts have been usedto treat human diseases since ancient time. Some plants have been reported to have additional medicinal value and beneficial characteristics including anti-inflammatory, immune-modulatory and anti-viral actions on hepatoprotective properties [3,4,5]. The secondary metabolites of herbal treatments have become more prominent for the treatment of liver disease, with evidencebased outcomes being established through promising clinical trials and validation
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