Most cited article: Contribution to Pharmacological Valorisation of Algerian Arctium minus (Hill) Bernh. Subsp. Atlanticum (Pomel) Maire; Antioxidant and Acetylcholinesterase Inhibitory Activities

Author(s):Sofiane Guettaf*, Abdelmoumen Benmerzoug, Bensouici Chawki, Yavuz Selim Çakmak, Saliha Dahamna, Abderrahmane Baghiani and Daoud Harzallah

Background: The traditional pharmacopoeia is full of potential resources for molecules with therapeutic effects involving the inhibition of enzymes linked to some diseases.

Objective: This work aimed to test in vitro neuroprotective activity against Alzheimer’s disease (AD) combined with the antioxidant effect of root extracts obtained by water, water/methanol, and ethyl acetate of the endemic Arctium minus. subsp. Atlanticum, a native of Algeria.

Methods: The different extracts of the root of the studied plant were obtained by decoction or maceration. The inhibitory effect of acetyl/butyrylcholinesterase (AChE/BChE) was achieved by a colorimetric method. Similarly, the antioxidant activity was measured based on several mechanisms: 1, 1- diphenyl-2-picryl-hydrazyl (DPPH) and galvinoxyl (GOR) radicals free scavenging assays, β-carotene bleaching inhibition activity, and cupric ion reducing antioxidant capacity (CUPRAC).

Results: In the various tests carried out, the ethyl acetate extract (EAE) possessed the most powerful antioxidant and anticholinesterase activities compared to the other samples. The IC₅₀ and A_0.5 values of DPPH, GOR, β-carotene, CUPRAC, anti-AChE, and anti-BChE assays were 69.45±5.49, 28.87±0.18, 121.58±16.76, 37.41±1.59, 265±21, and 240±6.3 μg / mL, respectively. Likewise, a correlation could be deduced between the type of extract and the potent antioxidant/anticholinesterase potential.

Conclusion: This work examines for the first time the anticholinesterase potential combined with the antioxidant effect of Algerian Arctium minus. subsp. Atlantic. This association between the two effects could be effective in the fight against AD, and therefore, the use of this natural resource may be possible in combating this aspect of neurodegeneration.

Read more: http://bit.ly/3JLRNNh

Most Cited Article – Ameliorative Effect of Acetyl L-carnitine in Alzheimer’s Disease via Downregulating of Homocysteine Levels in Hyperhomocysteinemia Induced Cognitive Deficit in Mouse Model

Author(s):Nisha Verma, Jeetendra Kumar Gupta, Krishna Kumar Varshney and Rajnish Srivastava*

Volume 14, Issue 3, 2021

Published on: 21 December, 2021

Page: [219 – 231]

Pages: 13

DOI: 10.2174/1872312814666211209102136

Abstract

Aims: The study was aimed at exploring the role of Acetyl L-Carnitine supplementation attenuating dementia and degradation of cognitive abilities in Hyperhomocysteinemia induced AD manifestations in the mouse model.

Background: Alzheimer’s disease (AD) is a neurological disorder that is marked by dementia, and degradation of cognitive abilities. There is great popularity gained by natural supplements as the treatment for AD, due to the higher toxicities of synthetic drugs. Hyperhomocysteinemia causes excitotoxicity to the cortical neurons, which brought us to the point that amino acids possibly have a role in causing cholinergic deformities, which are an important etiological parameter in AD. Acetyl L-Carnitine a methyl donor with the presence of three chemically reactive methyl groups linked to a nitrogen atom was found to possess neuroprotective activity against experimental models of AD.

Objective: The objective of the present investigation was to investigate and evaluate the pharmacological effect of Acetyl L-Carnitine against hyperhomocysteinemia induced Alzheimer’s disease (AD) in the mouse model.

Materials and Methods: The animals were divided into normal control (vehicle-treated), HHcy (dl-Homocysteine thiolactone treated) negative control, test group i.e., low dose (50mg/kg, p.o) of acetyl L-carnitine (L-ALC), high dose (100mg/kg,p.o) of acetyl L-carnitine (H-ALC), L-ALC+ SOV (Sodium orthovanadate) and H-ALC+SOV. HHcy was induced by administration of dl-Homocysteine thiolactone (dl-HCT; 1 g/kg, p.o.) on day-1 to day-15 of experimental schedule to all animals except normal control. The changes in the behaviour pattern of the animals due to neuroinflammation, and cholinergic dysfunction were examined in rotarod, novel objective recognition, passive avoidance, elevated plus maze, and morris water maze analysis. Biochemical investigation includes the estimation of total homocysteine (tHcy), Creatinine Kinase (CK), Acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and IL-6 and TNF-α.

Results: Supplementation of ALC in mouse considerably lowered the HHcy-induced AD manifestations in the experimental animals. It was found that ALC and SOV successfully diminished the behaviour abnormalities and lessened the Hcy-induced alteration in systemic Hcy levels, CK activity, and cholinergic dysfunction with improved bioenergetics in the Prefrontal cortex of the mice.

Conclusion: ALC was found to improve the HHcy-induced cognitive disabilities which was found to be associated with the decreased systemic levels of Hcy, CK, and cholinergic abnormalities. It also combats the oxidative stress-induced neuroinflammation with diminished pro-inflammatory markers in the pre frontal cortex. The outcomes collectively indicate ALC’s potential to be used as a supplementation in the pharmacotherapy of AD. Read now: https://bit.ly/3AHouVY

Most Cited Article – Molecular Docking and Dynamics Simulation of Natural Phenolic Compounds with GSK-3β: A Putative Target to Combat Mortality in Patients with COVID-19

Author(s):Zahra Khamverdi , Zeinab Mohamadi and Amir Taherkhani *

Volume 15, Issue 1, 2021

Published on: 15 December, 2021

Page: [16 – 34]Pages: 19

DOI: 10.2174/1872213X14666210916161447

Abstract

Objective: In this study, molecular docking analysis was performed to evaluate the binding affinity of 52 plant-based phenolics with the GSK-3β active sites. Moreover, Molecular Dynamics (MD) simulation was conducted to investigate the stability of interactions between the topranked phenolics and residues within the GSK-3β active sites.

Methods: Molecular docking and MD simulations were performed using AutoDock and Discovery Studio Client software, respectively. Thereafter, pharmacokinetic and toxicological properties of top inhibitors were predicted using bioinformatics web tools. This study aimed to identify the most effective amino acids involved in the inhibition of GSK-3β based on the most stabilizing interactions between the residues and compounds, and also by considering the degree centrality in the ligand- amino acid interaction network for GSK-3β.

Results: It was observed that procyanidin and amentoflavone could bind to the GSK-3β active sites at the picomolar (pM) scale as well as the binding affinity of ΔG _binding < -13 kcal/mol, while the inhibition constant for theaflavin 3’-gallate, procyanidin B4, and rutin was calculated at the nanomolar (nM) scale, suggesting that these phenolic compounds can be considered as potential effective GSK-3β inhibitors. Furthermore, Val70, Ala83, Val135, and Tyr134 were found to be the most important amino acids involved in the inhibition of GSK-3β.

Conclusion: The results of the current study may be useful in the prevention of several human disorders, including COVID-19, cancers, Alzheimer’s disease, diabetes mellitus, and cardiovascular diseases. However, wet-lab experiments need to be performed in the future. Read now: https://bit.ly/3RXNW1A