Rôle des cascades des MAP kinases dans la réponse aux lésions du nerf sciatique de rat

Nous avons montré que l activation des voies de signalisation p38 MAP kinase et Erk prend place très vite dans le nerf sciatique de rat après la lésion du nerf. Cette activation est détectable dès 3 minutes et est maximale à 15 minutes. Elle prend place dans le fragment distal comme dans le fragment proximal. Erk activé n est pas présent dans les axones mais il est visible dans les cellules non neuronales et notamment les cellules de Schwann. Nous avons montré d une part que la lésion induit en quelques heures l expression de plusieurs facteurs (NGF, LIF, IL-6, D2, D3) dans le nerf maintenu en survie (modèle ex vivo) comme il a été observé in vivo, et d autre part que la lésion du nerf active les voies p38 MAP kinase et Erk dés 15 minutes. Nous avons ensuite montré, que l expression des gènes D3 et LIF est réduite par l inhibition de la voie p38 impliquant ainsi cette voie dans la régulation de ces gènes. L inhibition de la voie Erk réduit l expression des gènes D3, LIF et NGF.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

ANTIMOTOLITY EFFECT OF ORGANIC EXTRACTS OF ANTHEMIS MAURITIANA MAIRE & SENNEN FLOWERS ON THE RODENT ISOLATED JEJUNUM

 Objective: The aim of the present study was to investigate the effect of the organic extracts of Anthemis mauritiana (AM) Maire and Sennen (Asteraceae)flowers on the contractile responses of the rabbit and rat jejunums and its possible mechanisms.Methods: Soxhlet extraction with different successive solvents (petroleum ether, dichloromethane, ethyl acetate, and methanol) were prepared andevaluated by preliminary phytochemical test. Antispasmodic effects of the extracts were evaluated against spontaneous contractions of rabbit and ratjejunum contracted by carbachol and high K+ concentration.Results: The phytochemical screening analysis revealed that the extracts of AM flowers contain flavonoids and tannins with variable quantities.Petroleum ether and dichloromethane extracts showed the most relaxant effects in the rabbit jejunum at concentrations with IC50 value of 9.31±2.65 μg/mland 25.04±5.87 μg/ml respectively. Ethyl acetate showed a total inhibition at 1 mg/ml, but the methanol extract at 5 mg/ml. In contrast, the residualaqueous extract was a reverse activity. And also all extracts caused an inhibitory effect on both K+ (75 mM) and CCh (10−6 M )induced contractions inthe rat jejunum except aqueous fraction. The extracts that have antispasmodic activity induced a marked depression on cumulative concentrationresponsecurve for carbachol and CaCl2.Conclusions: The results indicate that the antispasmodic effect decreased with the polarity of the organic extracts, but the aqueous fraction hada reverse effect. These results explain and confirm the popular use of genus of this plant for the treatment of gastrointestinal disturbances, andencourage studies on new compounds, in order to obtain new antispasmodic agents.Keywords: Anthemis mauritiana, Organic extract, Antispasmodic, Smooth muscle.Â

Exploring Medicinal Herbs’ Therapeutic Potential and Molecular Docking Analysis for Compounds as Potential Inhibitors of Human Acetylcholinesterase in Alzheimer’s Disease Treatment

Background and Objectives: Alzheimer’s disease (AD) stands as a pervasive neurodegenerative ailment of global concern, necessitating a relentless pursuit of remedies. This study aims to furnish a comprehensive exposition, delving into the intricate mechanistic actions of medicinal herbs and phytochemicals. Furthermore, we assess the potential of these compounds in inhibiting human acetylcholinesterase through molecular docking, presenting encouraging avenues for AD therapeutics. Materials and Methods: Our approach entailed a systematic exploration of phytochemicals like curcumin, gedunin, quercetin, resveratrol, nobiletin, fisetin, and berberine, targeting their capability as human acetylcholinesterase (AChE) inhibitors, leveraging the PubChem database. Diverse bioinformatics techniques were harnessed to scrutinize molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and adherence to Lipinski’s rule of five. Results: Results notably underscored the substantial binding affinities of all ligands with specific amino acid residues within AChE. Remarkably, gedunin exhibited a superior binding affinity (−8.7 kcal/mol) compared to the reference standard. Conclusions: These outcomes accentuate the potential of these seven compounds as viable candidates for oral medication in AD treatment. Notably, both resveratrol and berberine demonstrated the capacity to traverse the blood-brain barrier (BBB), signaling their aptitude for central nervous system targeting. Consequently, these seven molecules are considered orally druggable, potentially surpassing the efficacy of the conventional drug, donepezil, in managing neurodegenerative disorders

LC–MS/MS Phytochemical Profiling, Antioxidant Activity, and Cytotoxicity of the Ethanolic Extract of <i>Atriplex halimus</i> L. against Breast Cancer Cell Lines: Computational Studies and Experimental Validation

Atriplex halimus L., also known as Mediterranean saltbush, and locally as “Lgtef”, an halophytic shrub, is used extensively to treat a wide variety of ailments in Morocco. The present study was undertaken to determine the antioxidant activity and cytotoxicity of the ethanolic extract of A. halimus leaves (AHEE). We first determined the phytochemical composition of AHEE using a liquid chromatography (LC)–tandem mass spectrometry (MS/MS) technique. The antioxidant activity was evaluated using different methods including DPPH scavenging capacity, β-carotene bleaching assay, ABTS scavenging, iron chelation, and the total antioxidant capacity assays. Cytotoxicity was investigated against human cancer breast cells lines MCF-7 and MDA-MB-231. The results showed that the components of the extract are composed of phenolic acids and flavonoids. The DPPH test showed strong scavenging capacity for the leaf extract (IC50 of 0.36 ± 0.05 mg/mL) in comparison to ascorbic acid (IC50 of 0.19 ± 0.02 mg/mL). The β-carotene test determined an IC50 of 2.91 ± 0.14 mg/mL. The IC50 values of ABTS, iron chelation, and TAC tests were 44.10 ± 2.92 TE µmol/mL, 27.40 ± 1.46 mg/mL, and 124 ± 1.27 µg AAE/mg, respectively. In vitro, the AHE extract showed significant inhibitory activity in all tested tumor cell lines, and the inhibition activity was found in a dose-dependent manner. Furthermore, computational techniques such as molecular docking and ADMET analysis were used in this work. Moreover, the physicochemical parameters related to the compounds’ pharmacokinetic indicators were evaluated, including absorption, distribution, metabolism, excretion, and toxicity prediction (Pro-Tox II)