Molecular interaction of lavender (Lavandula angustifolia Mill) essential oil compounds as potential anxiolytic against α2δ subunit voltage gated calcium channel

The effect of brain area connectivity caused by an imbalance of the glutamate neurotransmitter in the brains patients experiencing anxiety is determined by α2δ subunit calcium channel activity. Lavender (Lavandula angustifolia) has been investigated to have anxiolytic effects on in vitro studies by its modulation through GABA, NMDA, and serotonin receptors, especially in the amygdala and hippocampus. However, the molecular mechanism of Lavender small molecules to reduce anxiety through calcium channels remains unclear. This study aims to evaluate lavender essential oil compounds which are potentially anxiolytic through the in-silico approach as an inhibitor of the α2δ subunit VGCC. Compound tabulations were obtained from earlier studies and collected from Pubchem database, while the three-dimensional structure of α2δ the subunit was retrieved from RCSB PDB. The physicochemical properties of the compounds were analyzed by using SwissADME and pkCSM. Binding affinity screening and molecular interaction analysis were conducted through CB-Dock web server. From 32 compounds demonstrated for docking against α2δ VGCC, four of them including geranyl formate, neryl alcohol, and phellandral have most binding site similarities compared to pregabalin by pointing at Arg217. This residue was known to exerts the pharmacological action of pregabalin to reduce anxiety and pain. The binding affinity of the geranyl formate (-6,6 kcal/mol), neryl alcohol (-6,4 kcal/mol), and phellandral (-6,2 kcal/mol) were comparable to pregabalin (-6,8 kcal/mol). Molecular dynamic was indicated to predict conformational change of α2δ subunit after superimposed. Thus, current study was indicated that geranyl formate, neryl alcohol, and phellandral as lavender essential oil small molecules has potent beneficial function as anxiolytic potential candidate.