"Assessment of Neuromodulatory Effects of Origanum punonense Danin Essential Oil on AMPA Receptor Function Using Whole-Cell Patch-Clamp Technique" Raw Data

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Ortho versus Meta Chlorophenyl-2,3-Benzodiazepine Analogues: Synthesis, Molecular Modeling, and Biological Activity as AMPAR Antagonists

2,3-Benzodiazepine compounds are an important family of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonists that act in a noncompetitive manner. Due to the critical role of AMPARs in the synapse and various neurological diseases, significant scientific interest in elucidating the molecular basis of the function of the receptors has spiked. The analogues were synthesized to assess the functional consequence of removing the amine group of the phenyl ring, the potency and efficacy of inhibition by substituting a halogen group at the meta vs ortho position of the phenyl ring, and layout the prediction of potential drug candidates for AMPAR hyperactivation. Using the whole-cell patch-clamp technique, we assessed the effect of the derivative on the amplitude of various AMPA-type glutamate receptors and calculated the desensitization and deactivation rates before and after treatment of HEK293 cells. We noticed that the amino group is not necessary for inhibition as long as an electron-withdrawing group is placed on the meta position of the phenyl ring of BDZ. Furthermore, compound 4a significantly inhibited and affected the desensitization rate of the tested AMPARs but showed no effect on the deactivation rate. The current study paves the way to a better understanding of AMPARs and provides possible drug candidates of 2,3-BDZ different from the conventional derivatives

Bactericidal, Fungicidal, Helminthicidal, Antioxidant, and Chemical Properties of <i>Chrozophora obliqua</i> Extract

Plants have been used by human being in the treatment and prophylaxis of various diseases since thousands of years ago. Chrozophora obliqua is an aromatic plant that possesses beneficial health properties in traditional medicine. However, other properties of Chrozophora obliqua such as antioxidant, antimicrobial, and helminthicidal properties have never been investigated earlier; therefore, the current study aimed to investigate these effects. The chemical composition of the crude extract isolated from Chrozophora obliqua by hydrodistillation was estimated by gas chromatography–mass spectrometry apparatus (GC-MS). The antiradical property was evaluated using DPPH method. While bactericidal and fungicidal activities were assessed against eight bacterial and fungal American Type Culture Collection and clinically isolated pathogens using minimal inhibitory concentration (MIC) method.Moreover, the helminthicidal activity was determined against Pheretima posthuma worms of freshly isolated extract after 1 h, 6 h, and 24 h of extraction. The current study revealed that Chrozophora obliqua extract composed of 16 compounds and possessed potential antiradical activity with an average IC50 value of 4.4 μg/ml almost at all time points. MIC values of the extract against Staphylococcus aureus, MRSA, Shigella sonnei, Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, Candida albicans,and Epidermophyton floccosum were approximately 1.5, 6.25, 12.5, 3.25, .015, 12.5, 6.25, and 1.125 mg/ml almost at all investigated time points. Also, it is found that 4, 10, 20, 40, 80, and 100 mg/ml of the extract needed 27.7, 13.5, 9.1, 7.8, and 4.4 min, respectively, to paralyze the investigated worm and needed 77.1, 37.7, 19.3, 13, and 9.9 min, respectively, to cause death to the studied worms. Our study provides evidence for the first time that Chrozophora obliqua extract possesses antiradical, bactericidal, fungicidal, and helminthicidal effects. These findings suggest that Chrozophora obliqua is a good choice for further pharmacological and clinical studies.</jats:p

Antidiabetic, antioxidant, and anti-obesity effects of phenylthio-ethyl benzoate derivatives, and molecular docking study regarding α-amylase enzyme

AbstractIn addition to their wide therapeutic application, benzoates and benzoic acid derivatives are the most commonly utilized food preservatives. The purpose of this study was to estimate the antioxidant, anti-diabetic, and anti-obesity activities of four 2-(phenylthio)-ethyl benzoate derivatives utilizing standard biomedical assays. The results revealed that the 2a compound has potent antidiabetic activity through the inhibition of α-amylase and α-glycosidase with IC50 doses of 3.57 ± 1.08 and 10.09 ± 0.70 µg/ml, respectively, compared with the positive control acarbose (IC50 = 6.47 and 44.79 µg/ml), respectively. In addition, by utilizing the β-carotene linoleic acid and DPPH methods, the 2a compound showed the highest antioxidant activity compared with positive controls. Moreover, the 2a compound showed potential anti-lipase activity with an IC50 dose of 107.95 ± 1.88 µg/ml compared to orlistat (IC50 = 25.01 ± 0.78 µg/ml). A molecular docking study was used to understand the interactions between four derivatives of (2-(phenylthio)-ethyl benzoate with α-amylase binding pocket. The present study concludes that the 2a compound could be exploited for further antidiabetic, antioxidant, and anti-obesity preclinical and clinical tests and design suitable pharmaceutical forms to treat these global health problems.</jats:p

SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

Summary: Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity. : Matt et al. show that mice lacking the AMPAR-associated protein SynDIG4/Prrt1 display deficits in synaptic plasticity and cognition. SynDIG4 modifies AMPAR biophysical properties in heterologous cells, but synaptic AMPAR kinetics are unchanged, suggesting that SynDIG4 establishes a pool of extrasynaptic AMPARs necessary for higher-order cognitive plasticity. Keywords: Prrt1, NG5, SynDIG4, SynDIG family, extrasynaptic AMPARs, auxiliary factor, hippocampus, excitatory synapse, LT

SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function.

Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only&nbsp;25%. Furthermore, SynDIG4 KO mice exhibit deficits&nbsp;in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity