1,8-cineole in Java cardamom essential oil selectively inhibits orexin receptors (OX1R/OX2R): Molecular docking and dynamics

Purpose: To determine the insomnia therapeutic potential of compounds contained in Java cardamom essential oil (JCEO) by targeting orexin-1/2 (OX-1/OX-2) receptors using molecular docking and dynamics. Methods: Forty compounds from GC-MS analysis of Java cardamom essential oil were retrieved from the database, docked with orexin-1 and 2 receptors, and their interactions analyzed. Molecular dynamics simulations were carried out to study the inhibitor binding interactions of the compounds with the best docking score using OpenMM in Google Colab. Results: Java cardamom essential oil compounds are bound to the sites where native ligands bind on orexin-1 (OX-1) and orexin-2 (OX-2) receptors. The binding affinity of JCEO compounds tends to be relatively selective towards orexin-2 (OX2R). 1,8-cineole is the best in its selectivity towards orexin-2 and the most stable. Conclusion: 1,8-cineole in JCEO could treat insomnia through selective inhibition of OX2R.