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Purpose <p>Delirium-associated sleep disorder is often linked to circadian rhythm dysregulation, in which the melatonin 1 (MT1) receptor plays a central role. The purpose of this study was to investigate the agonistic potential of <i>Avena sativa</i> derived phytocompounds against the MT1 receptor and to identify promising natural candidates for managing delirium-related sleep disturbances using in silico approaches.</p> Methods <p>Phytocompounds derived from <i>A. sativa</i> were initially screened using the IMMPAT 2.0 server. Selected compounds, namely luteolin, apigenin, tricin, isovitexin, and vitexin, were docked against the MT1 receptor using PyRx 0.8. Pharmacokinetic and toxicity profiling were performed using Deep-PK and ProTox-III to assess ADME/T properties. Drug-likeness was evaluated based on Lipinski’s rule of five, and blood–brain barrier permeability was assessed using the MolSoft server. Molecular interactions were visualised and analysed using Discovery Studio. Molecular dynamics (MD) simulations were conducted to evaluate the stability of ligand-MT1 receptor complexes in comparison with the reference drug ramelteon.</p> Results <p>All five phytocompounds exhibited favourable docking scores ranging from − 7.9 to − 9.6&#xa0;kcal/mol. Tricin showed unfavourable drug-likeness properties, while isovitexin and vitexin failed to meet acceptable toxicity criteria. Apigenin and luteolin demonstrated strong binding affinity, favourable pharmacokinetic profiles, acceptable toxicity and stable interactions with key MT1 receptor residues. MD simulation results revealed that both apigenin and luteolin formed stable complexes with the MT1 receptor, which were comparable to ramelteon. Luteolin exhibited slightly enhanced compactness, while apigenin showed stability closely resembling the standard ligand.</p> Conclusion <p>The findings suggest that apigenin and luteolin are promising modulators of the MT1 receptor with potential therapeutic relevance for delirium-associated sleep disorders. However, further in vitro and in vivo studies are required to validate their efficacy and safety.</p>

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Identification of Natural Flavonoids Apigenin and Luteolin as Potential MT1 Receptor Modulators for Delirium-Associated Sleep Disorder: An In-Silico Study

  • 期刊论文

  • 发表日期：

    2026年5月5日

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  • Mohsin Hussain,
  • Shifa Zahid,
  • Saad Ayubi,
  • Tauseef Reza,
  • Atik Yusuf,
  • Kashif Abbas,
  • Mudassir Alam

摘要

Purpose

Delirium-associated sleep disorder is often linked to circadian rhythm dysregulation, in which the melatonin 1 (MT1) receptor plays a central role. The purpose of this study was to investigate the agonistic potential of Avena sativa derived phytocompounds against the MT1 receptor and to identify promising natural candidates for managing delirium-related sleep disturbances using in silico approaches.

Methods

Phytocompounds derived from A. sativa were initially screened using the IMMPAT 2.0 server. Selected compounds, namely luteolin, apigenin, tricin, isovitexin, and vitexin, were docked against the MT1 receptor using PyRx 0.8. Pharmacokinetic and toxicity profiling were performed using Deep-PK and ProTox-III to assess ADME/T properties. Drug-likeness was evaluated based on Lipinski’s rule of five, and blood–brain barrier permeability was assessed using the MolSoft server. Molecular interactions were visualised and analysed using Discovery Studio. Molecular dynamics (MD) simulations were conducted to evaluate the stability of ligand-MT1 receptor complexes in comparison with the reference drug ramelteon.

Results

All five phytocompounds exhibited favourable docking scores ranging from − 7.9 to − 9.6 kcal/mol. Tricin showed unfavourable drug-likeness properties, while isovitexin and vitexin failed to meet acceptable toxicity criteria. Apigenin and luteolin demonstrated strong binding affinity, favourable pharmacokinetic profiles, acceptable toxicity and stable interactions with key MT1 receptor residues. MD simulation results revealed that both apigenin and luteolin formed stable complexes with the MT1 receptor, which were comparable to ramelteon. Luteolin exhibited slightly enhanced compactness, while apigenin showed stability closely resembling the standard ligand.

Conclusion

The findings suggest that apigenin and luteolin are promising modulators of the MT1 receptor with potential therapeutic relevance for delirium-associated sleep disorders. However, further in vitro and in vivo studies are required to validate their efficacy and safety.