Lavender essential oil constituents as antagonists of NR2B subunit of NMDA receptor: a molecular modeling and experimental approaches

[摘要] Background and Objectives Herbal plants are an important source of novel chemical drugs with therapeuticeffects. The present study aims to find the chemical compounds of the essential oil of lavender(Lavandula angustifolia Miller) and assess their antagonistic effects on N-methyl-D-aspartate receptor(NMDAR) subunit NR2B in the brain.Subjects and Methods The essential oil was first isolated by distillation method from flowering inflorescencesof lavender. Then, their chemical compounds were identifies by gas chromatography/massspectrometry (GC-MS). Molecular docking study and the evaluation of the molecular structures werecarried out on 20 compounds. Pyrx software, version 4.0 in Autodock Vina was used to perform themolecular docking of 20 ligands with NMDAR. The molecular structures of compounds were evaluatedin SwissADME website.Results In GC-MS, 41 active compounds were detected comprising 95.5% of the total essential oil oflavender plant. The highest amount was related to trans-carveol, followed by isopulegol, 1,3,8, -p-menthatriene,and isoborneol. In docking studies, results showed that the best ligands for binding to NMDARincluded trans-carveol, isopulegol, and 1,3,8, -p-menthatriene which demonstrated the higher affinity toactive site of the NMDAR. Ifenprodil, as an antagonist, shared common binding sites with camphor, thymol,alpha-phellandrene, limonene, gamma-3-carene, beta-thujone, trans-Carveol, beta-caryophyllene.Camphor, thymol, beta-thujone and trans-carveol had the highest gastrointestinal absorption, and transcarveolhad the lowest binding energy to NMDAR.Conclusion Camphor, thymol, beta-thujone, and trans-carveol are potential compounds of lavender essentialoil to inhibit NMDAR and improve learning and memory in neurodegenerative diseases.

[学科分类] 基础医学

[关键词] Alzheimer’s disease;lavender;Molecular docking;NMDA receptor;Antagonist