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 Atriplex halimus 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, ß-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 ß-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).

Thyroid hormone deiodinases in the central and peripheral nervous system.

Thyroid hormones play a critical role in development and functioning of the nervous system. Deiodinases (type 2 [D2] and type 3 [D3]) contribute to the control of thyroid hormone action in the nervous system by regulating the local concentrations of triiodothyronine (T(3)), the main active thyroid hormone. Most brain T(3) is indeed locally formed by deiodination of thyroxine (T(4)). This reaction is catalyzed by D2 expressed in astrocytes throughout the brain and in tanycytes in the mediobasal hypothalamus. D3, which inactivates both T(4) and T(3), is mainly expressed in neurons also throughout the brain, with high expression in hippocampus and pyriform cortex. The regulation of deiodinases by many factors in addition to the thyroid hormones indicate that their role is not limited to mitigate the fluctuations in plasma T(4) and T(3). In contrast to the brain, deiodinases are not expressed in the adult peripheral nerve. Nerve lesions induce D2 in peripheral nerve sheaths and D3 in the endoneurial compartment containing Schwann cells. On the basis of available data summarized in this review, D2 and D3 clearly contribute to determine T(3) concentrations depending on the area of the nervous system, the state of development, and the pathophysiologic conditions.