Lavandula dentata L. and Origanum syriacum L. essential oils have numerous health benefits and properties, such as possessing common components with a variant degree of depressive actions in the central nervous system. We investigated the depressive property of these oils on AMPA receptors, which are responsible for most of the fast-excitatory neurotransmission in the CNS and play a critical role in synaptic plasticity. Since excessive activation of AMPARs has been linked to neurotoxicity leading to various pathologies, we hypothesize that these oils have a neuroprotective role by acting directly on the kinetics of AMPARs. Using Gas Chromatography-Mass Spectrometry (GC/MS) and patch-clamp electrophysiology, the essential oils of L. dentata flowers and O. syriacum leaves were characterized and the whole cell currents were measured with and without the administration of the oils onto HEK293 cells. The current study results showed that the biophysical properties of AMPA receptor subunits showed a decrease in desensitization rate of GluA1 and GluA2 homomers, using O. syriacum, while administering L. dentata oil decreased the desensitization rate of GluA1 and GluA2 homomers, as well as GluA1/2 heteromers. As for the deactivation rate, both oils slowed the deactivation kinetics of all AMPA receptor subunits. Intriguingly, between the two oils, the effect of desensitization and deactivation was of a greater significance for L. dentata oil than O. syriacum. Our data suggest that the two oils contain components that are essential to identify, as those active components underlie the oils’ neuronal depressive properties reported, and to extract them to synthesize a potent neuroprotective drug to treat neurological diseases potentially.

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The development of efficacious and safe drugs for the treatment of neurological diseases related to glutamate toxicity has been a focus in neuropharmacological research. Specifically, discovering antagonists to modulate the activity and kinetics of AMPA receptors, which are the fastest ligand-gated ion channels involved in excitatory neurotransmission in response to glutamate. Thus, the current study investigated novel curcumin derivatives on the biophysical properties of AMPA receptors, specifically on the homomeric GluA2 and the heteromeric GluA2/A3 subunits and assessed for inhibitory actions. The biophysical parameter (i.e., desensitization, deactivation, and peak currents) were measured by using whole-cell patch clamp electrophysiology with and without the administration of the derivatives onto HEK293 cells. CR-NN, CR-NNPh, CR-MeNH, and CR-NO of the tested derivatives showed inhibition on all AMPA receptors up to 6 folds. Moreover, the inhibitory derivatives also increased desensitization and deactivation, which further intensifies the compounds’ neuroprotective effects. However, CR-PhCl, CR-PhF, and CR-PhBr did not show any significant changes on the peak current, deactivation or desensitization rates. By comparison to other discovered and widely used antagonist, the prepared curcumin derivatives are not selective to a specific AMPA subunit, instead implement its effect in the same way between all types of AMPA receptors. Additionally, the obtained results provide derivatives that not only noncompetitively inhibit AMPARs but also decrease its biophysical kinetics, specifically desensitization and deactivation rates. Hence, to potentially serve as a new AMPAR inhibitor with therapeutic potential, the current study provides compounds that are non-selective and non-competitive antagonist, which also effect the desensitization and deactivation rates of the receptor.

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ABSTRACT:Arum palaestinum is one of the famous wild plants that have been used since the ancient time in the Palestinian folk food and medicine. However, it needs particular cooking steps to decrease its numbing taste. We investigated the impact of cooking, measures on taste, total phenols and antioxidant activity of wild A. palaestinum by using an Alpha-Astree Electronic tongue (ET), which is used for food taste assessment. In this study, the A. palaestinum was cooked in different ways. We used Folin Ciocalteu's process to compare total phenols, where radical scavenging assay was used to evaluate the antioxidant activity using 2, 2-diphenyl-1-picrylhydrazyl-hydrate (DPPH). Our results showed that a very significant discrimination of the samples with different distances between groups (p-values < 0.001) in the ET results coupled with the principal component analysis (PCA). The samples were in the following order in term of numbing taste: Fresh > dried > cooked. Moreover, the pattern discrimination index between (A and C), (B and C) and (A and B) were 88%, 96.36%, and 98%, respectively, which suggests that C and A are the most similar preparations in term of taste, while B is the worst one. Our results reveal that the cooking and dried A. palaestinum showed a lower numbing taste by ET, while the antioxidant activities showed a marked correlation with the total phenolic contents. As a result, we concluded that the oven dried preparing method (home roasting) for A. palaestinum is the most efficient method for consumption or preparing bioactive supplements for nutraceutical and pharmaceutical supplements.