<i>In Silico</i> Evaluation of Bioactive Compounds from <i>Monodora myristica</i> (Gaertn.) Dunal Essential Oil as MT Melatonin Receptor Agonists for The 1 Management of Insomnia
DOI:
https://doi.org/10.51412/psnnjp.2026.025Keywords:
Monodora myristica, (Gaertn.) Dunal, Insomnia, MT receptor, Molecular docking, Essential oil, In silicoAbstract
Background: Sleep disorders remain a significant health challenge, with melatonin receptor 1 (MT ) 1 serving as a key target for pharmacological intervention. Previous in vivo study revealed that Monodora myristica (Gaertn.) Dunal essential oil prolonged total sleep time and reduced sleep latency in mice. This study investigated the potential of bioactive compounds from Monodora myristica essential oil as MT agonists for sleep management, using in silico approaches.
Method: Dried seeds were extracted to yield 19.4% essential oil (110.24 g from 567 g powdered material). GC-MS was used to identify constituents. Molecular docking was done against human MT1 crystal structure (PDB: 6ME5). Drug-likeness, pharmacokinetics, and toxicity of top compounds were predicted in silico.
Results: Twelve bioactive compounds were identified, with p-Cymene (31.16%), Tricyclene (17.35%), and alpha-Phellandrene (13.07%) as most abundant. Docking binding affinities ranged from -4.8 to -6.3 kcal/mol. Naphthalene had the strongest affinity (-6.3 kcal/mol), equal to melatonin (-6.3 kcal/mol), followed by p-Cymene (-5.9 kcal/mol). Caryophyllene and Alpha-Terpineol both scored -5.8 kcal/mol. Alpha-Terpineol had zero Lipinski violations, while Caryophyllene, p-Cymene, and Naphthalene had one each. All four had bioavailability score of 0.55 and good solubility. AlphaTerpineol showed high GI absorption, BBB permeability, and minimal CYP450 inhibition; others had low GI absorption. Toxicity: p-Cymene was Class I, LD50 3 mg/kg; Alpha-Terpineol was Class 5, LD50 2830 mg/kg.
Conclusion: Alpha-Terpineol is the most promising candidate based on binding affinity, drug likeness, pharmacokinetics, and low toxicity, and warrants further in vitro and in vivo validation for insomnia therapeutics.
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