COX inhibition: Catalepsy and Striatum Dopaminergic-GABAergic-Glutamatergic Neurotransmission

Selective COX-2 and COX-1 inhibitors were administered (i.p. acutely) to normal and parkinsonian rats, followed by the analysis of the striatal dopamine, GABA and glutamate concentrations using the microdialysis technique, simultaneously, the catalepsy of animals was evaluated. Selective COX-2 inhibition showed improving effects on the catalepsy followed by decreasing the striatum glutamatergic-GABAergic and enhancing the dopaminergic neurotransmission. Nonetheless COX inhibition had no significant improving effects on damaged Substantia Nigra Pars Compacta (SNc) neurons

Validation and Uncertainty Estimation of an Ecofriendly and Stability-Indicating HPLC Method for Determination of Diltiazem in Pharmaceutical Preparations

A green, simple, and stability-indicating RP-HPLC method was developed for the determination of diltiazem in topical preparations. The separation was based on a C18 analytical column using a mobile phase consisted of ethanol: phosphoric acid solution (pH = 2.5) (35 : 65, v/v). Column temperature was set at 50°C and quantitation was achieved with UV detection at 240 nm. In forced degradation studies, the drug was subjected to oxidation, hydrolysis, photolysis, and heat. The method was validated for specificity, selectivity, linearity, precision, accuracy, and robustness. The applied procedure was found to be linear in diltiazem concentration range of 0.5–50 μg/mL (r2=0.9996). Precision was evaluated by replicate analysis in which % relative standard deviation (RSD) values for areas were found below 2.0. The recoveries obtained (99.25%–101.66%) ensured the accuracy of the developed method. The degradation products as well as the pharmaceutical excipients were well resolved from the pure drug. The expanded uncertainty (5.63%) of the method was also estimated from method validation data. Accordingly, the proposed validated and sustainable procedure was proved to be suitable for routine analyzing and stability studies of diltiazem in pharmaceutical preparations

Benzofuranone Derivatives as Effective Small Molecules Related to Insulin Amyloid Fibrillation: A Structure-Function Study

Amyloids are protein fibrils of nanometer size resulting from protein self-assembly. They have been shown to be associated with a wide variety of diseases such as Alzheimer\u27s and Parkinson\u27s and may contribute to various other pathological conditions, known as amyloidoses. Insulin is prone to form amyloid fibrils under slightly destabilizing conditions in vitro and may form amyloid structures when subcutaneously injected into patients with diabetes. There is a great deal of interest in developing novel small molecule inhibitors of amyloidogenic processes, as potential therapeutic compounds. In this study, the effects of five new synthetic benzofuranone derivatives were investigated on the insulin amyloid formation process. Protein fibrillation was analyzed by thioflavin-T fluorescence, Congo red binding, circular dichroism, and electron microscopy. Despite high structural similarity, one of the five tested compounds was observed to enhance amyloid fibrillation, while the others inhibited the process when used at micromolar concentrations, which could make them interesting potential lead compounds for the design of therapeutic antiamyloidogenic compounds. Amyloids are protein fibrils resulting from protein self-assembly and contribute to pathological conditions known as amyloidoses. Insulin is prone to form amyloid fibrils under in vivo conditions when injected in diabetic patients. In this study, the effects of five new synthetic benzofuranone derivatives were investigated on in vitro insulin amyloid formation. Despite high structural similarity, one of the five compounds tested was observed to enhance amyloid fibrillation while the others inhibited the process when used at micro molar concentrations. © 2011 John Wiley & Sons A/S

Chemodiversity of <i>Nepeta menthoides</i> Boiss. & Bohse. essential oil from Iran and antimicrobial, acetylcholinesterase inhibitory and cytotoxic properties of 1,8-cineole chemotype

<p>The essential oil of <i>Nepeta menthoides</i> Boiss. & Bohse., from Iran, was analysed by GC/MS. Two types of multivariate analyses were done based on the chemical composition of the investigated sample in this study and 12 other samples reported in the literature to show the chemodiversity in essential oil composition. Antimicrobial, acetylcholinesterase inhibitory and cytotoxic activities of the essential oil and its major component were assessed. Twenty-one compounds were identified, representing 96.81% of the total oil and the major constituent was 1,8-cineole (70.06%). Multivariate analyses revealed two chemotypes, i.e. nepetalactone and 1,8-cineole. The essential oil of the sample investigated in this study which was a 1,8-cineole chemotype and 1,8-cineole showed moderate antimicrobial activity and significantly inhibited the activity of acetylcholinesterase enzyme. Cytotoxicity evaluation against three breast cancer cell lines showed a potent inhibitory activity. Further investigations are necessary to confirm the variety in several populations of <i>N. menthoides</i>.</p