scholarly journals Identification of Polyphenolics from Loranthus globosus as Potential Inhibitors of Cholinesterase and Oxidative Stress for Alzheimer’s Disease Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Netish Kumar Kundo ◽  
Md. Imran Nur Manik ◽  
Kushal Biswas ◽  
Riniara Khatun ◽  
Md. Yusuf Al-Amin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inhibitory Activity ◽  
Folk Medicine ◽  
Disease Treatment ◽  
Potential Source ◽  
Cholinesterase Inhibitory Activity ◽  
Potential Inhibitors ◽  
Crude Methanol Extract ◽  
And Oxidative Stress

Mistletoes are considered to be the potential medicinal herbs due to their rich traditional uses. Loranthus globosus is a Bangladeshi mango mistletoe that has been reported as folk medicine for various ailments and diseases. In an attempt to explore its effectiveness in Alzheimer’s disease (AD), we investigated the antioxidant and acetylcholinesterase inhibitory activity of L. globosus. We report that the crude methanol extract (CME) of the plant contains a good amount of polyphenolics and possesses antioxidant and cholinesterase inhibitory activity. Fractionation of CME with solvents of varying polarity revealed the highest activity and polyphenolic content in the ethylacetate fraction (EAF). Correlation analysis revealed a significant ( P < 0.05 ) association of polyphenolics with the antioxidant and cholinesterase inhibitory properties. Using column chromatography with diaion resin, the polyphenolics (EAF-PP) were isolated from the EAF that displayed the potent antioxidant and cholinesterase inhibitory activities. Kinetic analysis showed that EAF-PP exhibited a competitive type of inhibition. A total of thirty-six compounds including catechin and its different derivatives were identified in the EAF-PP by LC/MS analysis. Bioactivity-guided separation approach afforded the isolation of the two major active compounds catechin and catechin dimer from the EAF-PP. Hence, EAF-PP represents a potential source of antioxidants and cholinesterase inhibitors, which can be used in the management of AD.

Design, Synthesis and Biological Evaluation of New Cycloalkyl Fused Quinolines Tethered to Isatin Schiff Bases as Cholinesterase Inhibitors

2020 ◽  
Vol 23 ◽  
Author(s):  
Baswaraju Macha ◽  
Ravindra Kulkarni ◽  
Anil Kumar Garige ◽  
Rambabu Palabindala ◽  
Raghuramrao Akkinepally ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Schiff Bases ◽  
Active Site ◽  
Inhibitory Activity ◽  
Docking Studies ◽  
Behavioral Studies ◽  
Cholinesterase Inhibitory Activity ◽  
Butyryl Cholinesterase

Aims and Objective: Alzheimer’s disease is now a most prevalent neuro degenerative disease of central nervous system leading to dementia in elderly aged population. Numerous pathological changes have been associated in the progression of Alzheimer’s disease. One of such pathological hypothesis is declined cholinergic activity which eventually affects cognitive and memory deficits. Inhibition cholinesterases will apparently elevate acetyl choline levels which is benefactor on cognitive symptoms of the disease. This manuscript describes the new tacrine derivatives tethered to isatin Schiff bases through alkanoyl linker and screened for cholinesterase inhibitory activity. Materials and Methods: Tacrine and two more cycloalkyl ring fused quinolones were synthesized and converted to Ncycloalkyl fused quinoline chloroamides. Isatin Schiff bases were also synthesized by the reaction between isatin and substituted aromatic anilines and in subsequent reaction, isatin Schiff bases were reacted with cycloalkyl fused quinolones to afford anticipated compounds 10a-i, 11a-i and 12a-i. All the compounds have been screened for acetyl and butyryl cholinesterase inhibitory activity and in vivo behavioral studies. Binding interactions of the desired compounds have also been studied by docking them in active site of both cholinesterases. Results: Three compounds 12d, 12e and 12h with propionyl and butyroyl linker between amine and isatin Schiff base scaffold have shown potent acetyl and butyryl cholinesterase inhibitory activity. However most potent cholinesterase inhibitor was 13d with IC50 value of 0.71±0.004 and 1.08±0.02 μM against acetyl and butyryl cholinesterases respectively. The hepatotoxicity of potent compounds revealed that the tested compounds were less hepatotoxic than tacrine and also exhibited encouraging in vivo behavioral studies in test animals. Docking studies of all the molecules disclosed close hydrogen bond interactions within the binding site of both cholinesterases. Conclusion: New cycloalkyl fused quinolones tethered with alkoyl linker to isatin Schiff bases endowed significant and potent cholinesterase inhibitory activities. Few of the compounds have also exhibited lesser hepatotoxicity and all the synthesized compounds were good in behavioral studies. Molecular docking studies also indicated close interactions in active site of cholinesterases.

Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones

2015 ◽  
Vol 13 (36) ◽  
pp. 9418-9426 ◽  
Author(s):  
Marina Y. Fosso ◽  
Harry LeVine 3rd ◽  
Keith D. Green ◽  
Oleg V. Tsodikov ◽  
Sylvie Garneau-Tsodikova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inhibitory Activity ◽  
Metal Binding ◽  
Acetylcholinesterase Activity ◽  
Structural Modifications ◽  
Chalcone Derivatives ◽  
Cholinesterase Inhibitory Activity

Twenty chalcone derivatives were synthesized and found to bind Cu2+and Zn2+ions, modulate the dissociation of Aβ aggregates, and inhibit acetylcholinesterase activity. These chalcones show promise for the development of probes and/or therapeutics for Alzheimer's disease.

Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

2019 ◽  
Vol 19 (8) ◽  
pp. 688-705
Author(s):  
Taibi Ben Hadda ◽  
Abdur Rauf ◽  
Hsaine Zgou ◽  
Fatma Sezer Senol ◽  
Ilkay Erdogan Orhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Metal Accumulation ◽  
Microtiter Plate ◽  
Metal Chelation ◽  
Carbonyl Derivatives ◽  
Cholinesterase Inhibitory Activity ◽  
Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

Alpha-1-Antichymotrypsin: a Common Player for Type 2 Diabetes and Alzheimer's Disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Regulatory Networks ◽  
Therapeutic Strategies ◽  
Oxidative Stresses ◽  
Bibliographic Search ◽  
And Oxidative Stress

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.

scholarly journals Antia, a Natural Antioxidant Product, Attenuates Cognitive Dysfunction in Streptozotocin-Induced Mouse Model of Sporadic Alzheimer’s Disease by Targeting the Amyloidogenic, Inflammatory, Autophagy, and Oxidative Stress Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Nesrine S. El Sayed ◽  
Mamdooh H. Ghoneum
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Protective Effect ◽  
Cognitive Dysfunction ◽  
Protective Role ◽  
Sporadic Alzheimer’S Disease ◽  
Stat3 Pathway ◽  
And Oxidative Stress

Background. Many neurodegenerative diseases such as Alzheimer’s disease are associated with oxidative stress. Therefore, antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Objective. We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer’s disease (SAD) induced in mice. Antia is a natural product that is extracted from the edible yamabushitake mushroom, the gotsukora and kothala himbutu plants, diosgenin (an extract from wild yam tubers), and amla (Indian gooseberry) after treatment with MRN-100. Methods. Single intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg) was used for induction of SAD in mice. Antia was injected intraperitoneally (i.p.) in 3 doses (25, 50, and 100 mg/kg/day) for 21 days. Neurobehavioral tests were conducted within 24 h after the last day of injection. Afterwards, mice were sacrificed and their hippocampi were rapidly excised, weighed, and homogenized to be used for measuring biochemical parameters. Results. Treatment with Antia significantly improved mice performance in the Morris water maze. In addition, biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Further studies with western blot showed the protective effect of Antia for the JAK2/STAT3 pathway. Conclusions. Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD.

Huprine Y – tryptophan heterodimers with potential implication to Alzheimer’s disease treatment

2021 ◽  
pp. 128100
Author(s):  
Eva Mezeiova ◽  
Martina Hrabinova ◽  
Vendula Hepnarova ◽  
Daniel Jun ◽  
Jana Janockova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Treatment ◽  
Potential Implication
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