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The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its pathway in mammals is limited. In the present study, the binding of AGO and its key compounds, methyl eugenol, 1,8-cineole, and 4-allylphenyl acetate, to gamma-aminobutyric acid type A (GABAA) receptors in rat cortical membranes, was investigated using a [3H]muscimol binding assay and an in silico modeling platform. The results showed that only AGO and methyl eugenol displayed a positive modulation at the highest concentrations, whereas 1,8-cineole and 4-allylphenyl acetate were inactive. The result of AGO correlated well to the amount of methyl eugenol in AGO. Computational docking and dynamics simulations into the GABAA receptor complex model (PDB: 6X3T) showed the stable structure of the GABAA receptor–methyl eugenol complex with the lowest binding energy of −22.16 kcal/mol. This result shows that the anesthetic activity of AGO and methyl eugenol in mammals is associated with GABAA receptor modulation. An oil-in-water nanoemulsion containing 20% w/w AGO (NE-AGO) was formulated. NE-AGO showed a significant increase in specific [3H]muscimol binding, to 179% of the control, with an EC50 of 391 µg/mL. Intracellular studies show that normal human cells are highly tolerant to AGO and the nanoemulsion, indicating that NE-AGO may be useful for human anesthesia. [ABSTRACT FROM AUTHOR]

Inhibition of P-glycoprotein (P-gp)’s function may conduct significant changes in the prescription drugs’ pharmacokinetic profiles and escalate potential risks in taking place of drug/herb-drug interactions. Computational modeling was advanced to scrutinize some bioflavonoids which play roles in herb-drug interactions as P-gp inhibitors utilizing molecular docking and pharmacophore analyses. Twenty-five flavonoids were utilized as ligands for the modeling. The mouse P-gp (code: 4Q9H) was acquired from the PDB. The docking was operated utilizing AutoDock version 4.2.6 (Scripps Research Institute, La Jolla, CA) against the NBD2 of 4Q9H. The result illustrated the high correlation between the docking scores and observed activities of the flavonoids and the putative binding site of these flavonoids was proposed and compared with the site for ATP. To evaluate hotspot amino acid residues within the NBD2, Binding modes for the ligands were achieved using LigandScout to originate the NBD2-flavonoid pharmacophore models. The results asserted that these inhibitors competed with ATP for binding site in the NBD2 (as competitive inhibitors) including the hotspot residues which associated with electrostatic and van der Waals interactions with the flavonoids. In MD simulation of eight delegated complexes selected from the analyzed flavonoid subclasses, RMSD analysis of the trajectories indicated the residues were stable throughout the duration of simulations. [ABSTRACT FROM PUBLISHER]