The Binding of <i>Alpinia galanga</i> Oil and Its Nanoemulsion to Mammal GABA_A Receptors Using Rat Cortical Membranes and an In Silico Modeling Platform

• Main Authors: Nattakanwadee Khumpirapang (Author), Krit Suknuntha (Author), Pathomwat Wongrattanakamon (Author), Supat Jiranusornkul (Author), Songyot Anuchapreeda (Author), Petrine Wellendorph (Author), Anette Müllertz (Author), Thomas Rades (Author), Siriporn Okonogi (Author)
• Format: Book
• Published: MDPI AG, 2022-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

The anesthetic effect of <i>Alpinia galanga</i> 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 (GABA_A) 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 GABA_A receptor complex model (PDB: 6X3T) showed the stable structure of the GABA_A 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 GABA_A 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.

Item Description

10.3390/pharmaceutics14030650
1999-4923