Salvia palaestina Essential Oil as a Molecular Modulator of AMPA Receptors

Introduction Phytochemicals, particularly those from Salvia species, exhibit notable neuroprotective effects by modulating neurotransmission and limiting excitotoxic damage. Since excessive glutamate release and overactivation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors contribute to neuronal injury, targeting these receptors presents a promising molecular approach. This study investigates the modulatory effects of Salvia palaestina essential oil on AMPA receptor subunits to elucidate its potential role in regulating excitatory synaptic signaling.

Methods Human embryonic kidney 293T cells were transiently transfected with the DNA of four AMPA receptor subunits (GluA1, GluA2, GluA1/2, and GluA2/3) using jetPRIME. Enhanced green fluorescent protein aided expression tracking. After 36 hours, fluorescence-sorted cells were plated for whole-cell patch-clamp recordings. Currents were evoked by 10 mM glutamate with or without Salvia palaestina essential oil, and whole-cell current responses along with deactivation and desensitization kinetics were analyzed using SutterPatch and Igor Pro7 software.

Results Whole-cell recordings revealed that Salvia palaestina essential oil markedly inhibited AMPA receptor activity across all tested subunits. Current amplitudes were reduced approximately 5-fold in GluA1, GluA1/2, and GluA2/3 and 6-fold in GluA2. The oil also altered receptor kinetics, increasing deactivation rates nearly 3-fold in all subunits while slowing desensitization 4-fold in GluA2, 3-fold in GluA2/3, 2.2-fold in GluA1, and 1.4-fold in GluA1/2, indicating strong modulatory effects on receptor function.

Conclusions Salvia palaestina essential oil strongly modulates AMPA receptor function by reducing whole-cell currents and altering deactivation and desensitization kinetics. These effects suggest anti-excitotoxic potential, likely mediated by major constituents such as carvacrol, eucalyptol, and thujones, supporting its role in regulating glutamatergic transmission and synaptic activity at the molecular level.