Bioactive compounds from Ocimum tenuiflorum and Poria cocos: A novel natural Compound for insomnia treatment based on A computational approach

• Published in: Computers in biology and medicine Vol. 175; p. 108491
• Main Authors: Ranteh, Onggan, Tedasen, Aman, Rahman, Md. Atiar, Ibrahim, Mohammed Auwal, Sama-ae, Imran
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.06.2024; Elsevier Limited
• Subjects: Amino acids; Benzodiazepines; Bioactive compounds; Bioavailability; Biocompatibility; Biological activity; Blood-brain barrier; Carboxylic acids; Cardiovascular diseases; Computational drug discovery; Computer applications; Drug dosages; Drug therapy; Drugs; Genetic algorithms; Herbal medicine; Humans; Insomnia; Internal Medicine; Libraries; Ligands; Medicinal plants; Molecular docking; Molecular Docking Simulation; Molecular dynamic simulations; Molecular dynamics; Molecular Dynamics Simulation; Neuropeptides; Ocimum - chemistry; Ocimum tenuiflorum; Orexin receptors; Orexins; Other; Pharmacokinetics; Pharmacology; Phenanthrene; Plant Extracts - chemistry; Plant Extracts - therapeutic use; Poria cocos; Proteins; Public health; Receptors; Simulation; Sleep deprivation; Sleep disorders; Sleep Initiation and Maintenance Disorders - drug therapy; Toxicity; Molecular dynamic simulations; Medicinal plants; Insomnia; Orexin receptors; Bioactive compounds; Computational drug discovery; Molecular docking; orexin receptors; molecular docking; molecular dynamic simulations; computational drug discovery; bioactive compounds; medicinal plants
• ISSN: 0010-4825; 1879-0534; 1879-0534
• DOI: 10.1016/j.compbiomed.2024.108491

Insomnia, a widespread public health issue, is associated with substantial distress and daytime functionality impairments and can predispose to depression and cardiovascular disease. Cognitive Behavioral Anti-insomnia therapies including benzodiazepines often face limitations due to patient adherence or potential adverse effects. This study focused on identifying novel bioactive compounds from medicinal plants, aiming to discover and develop new therapeutic agents with low risk-to-benefit ratios using computational drug discovery methods. Through a systematic framework involving compound library preparation, evaluation of drug-likeness and pharmacokinetics, toxicity prediction, molecular docking, and molecular dynamic simulations, two natural compounds such as 2-(4-hydroxy-3-methoxyphenyl)-8-methoxy-6-prop-2-enyl-3,4-dihydro-2H-chromen-3-ol from Ocimum tenuiflorum and 7-(2-hydroxypropan-2-yl)-1,4a-dimethyl-9-oxo-3,4,10,10a-tetrahydro-2H-phenanthrene-1-carboxylic acid from Poria cocos exhibited high binding affinity with orexin receptor type 1 (OX1R) and type 2 (OX2R), surpassing commercial drugs used in insomnia treatment. Additionally, they showed interactions with critical amino acid residues within the receptors that play crucial roles in competitive inhibitor activity, like commercial drugs such as Suvorexant, Lemborexant, and Daridorexant. Further, molecular dynamics simulations of the protein-ligand complexes under conditions that mimic the in vivo environment revealed both compounds' sustained and robust interactions with the OX1R and OX2R, reinforcing their potential as effective therapeutic candidates. Furthermore, upon evaluating both compounds' drug-likeness, pharmacokinetics, and toxicity profiles, it was discerned that they displayed considerable drug-like properties and favorable pharmacokinetics, along with diminished toxicity. The research provides a solid foundation for further exploring and validating these compounds as potential anti-insomnia therapeutics. [Display omitted] •This study deploys computational methods for insomnia drug discovery.•Bioactive compounds A and B were predicted as potential anti-insomnia properties.•Both the compounds mimic the actions of commercial competitive inhibitors.•Molecular dynamics simulations affirm their therapeutic potential.•Evaluation reveals drug-like properties and low toxicity.