TY - JOUR
T1 - The Binding of Alpinia galanga Oil and Its Nanoemulsion to Mammal GABA(A) Receptors Using Rat Cortical Membranes and an In Silico Modeling Platform
AU - Khumpirapang, Nattakanwadee
AU - Suknuntha, Krit
AU - Wongrattanakamon, Pathomwat
AU - Jiranusornkul, Supat
AU - Anuchapreeda, Songyot
AU - Wellendorph, Petrine
AU - Mullertz, Anette
AU - Rades, Thomas
AU - Okonogi, Siriporn
PY - 2022
Y1 - 2022
N2 - 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 (GABA(A)) receptors in rat cortical membranes, was investigated using a [H-3]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 [H-3]muscimol binding, to 179% of the control, with an EC50 of 391 mu g/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.
AB - 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 (GABA(A)) receptors in rat cortical membranes, was investigated using a [H-3]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 [H-3]muscimol binding, to 179% of the control, with an EC50 of 391 mu g/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.
KW - Alpinia galanga
KW - essential oil
KW - mammal anesthesia
KW - anesthetic pathway
KW - positive allosteric modulation
KW - binding assay
KW - CLOVE OIL
KW - METHYLEUGENOL
KW - ANTIOXIDANT
KW - 1,8-CINEOLE
KW - MODULATION
KW - ADSORPTION
KW - EXTRACTS
KW - RHIZOMES
KW - CURRENTS
KW - GLYCINE
U2 - 10.3390/pharmaceutics14030650
DO - 10.3390/pharmaceutics14030650
M3 - Journal article
C2 - 35336025
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
SN - 1999-4923
IS - 3
M1 - 650
ER -