Acetylcholinesterase Inhibitory Potential and Antioxidant Activities of Five Cultivars of Rosa Damascena Mill. From Isparta, Turkey

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impairment of language. Alzheimer's disease is strongly associated with oxidative stress and impairment in the cholinergic pathway, which results in decreased levels of acetylcholine in certain areas of the brain. Hence, inhibition of acetylcholinesterase activity has been recognized as an acceptable treatment against Alzheimer's disease. Nature provides an array of bioactive compounds, which may protect against free radical damage and inhibit acetylcholinesterase activity. This study compares the in vitro antioxidant and anticholinesterase activities of hydroalcoholic extracts of five cultivars of Rosa Damascena Mill. petals (R. damascena 'Bulgarica', R. damascena 'Faik', R. damascena 'Iranica', R. damascena 'Complex-635' and R. damascena 'Complex-637') from Isparta, Turkey. The antioxidant activities of the hydroalcoholic extracts were tested for ferric ion reduction and DPPH radical scavenging activities. The anti-acetylcholinesterase activity was also evaluated. All rose cultivars showed a high potency for scavenging free radical and inhibiting acetylcholinesterase activity. There was a significant correlation between antioxidant and acetylcholinesterase inhibitory activity. Among cultivars, Complex-635 showed the highest inhibitory effect with an IC50 value of 3.92 µg/mL. Our results suggest that all these extracts may have the potential to treat Alzheimer's disease with Complex-635 showing more promise.

Download Full-text

Claulansine F–Donepezil Hybrids as Anti-Alzheimer’s Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities

Molecules ◽

10.3390/molecules26051303 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1303

Author(s):

Yingda Zang ◽

Ke Liu ◽

Weiping Wang ◽

Chuangjun Li ◽

Jie Ma ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Free Radical ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Glucose Deprivation ◽

Free Radical Scavenging ◽

Neuroprotective Effects ◽

Catalytic Active Site

The multifactorial nature of Alzheimer’s disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F–donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC50) 1.63–4.62 μM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen–glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood–brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.

Download Full-text

Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential

Current Pharmaceutical Design ◽

10.2174/1381612826666201112144006 ◽

2020 ◽

Vol 26 ◽

Author(s):

Nimra Javaid ◽

Muhammad Ajmal Shah ◽

Azhar Rasul ◽

Zunera Chauhdary ◽

Uzma Saleem ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Ellagic Acid ◽

Molecular Mechanisms ◽

Neurodegenerative Disorder ◽

Therapeutic Potential ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Acetylcholinesterase Activity ◽

Neuroprotective Effects

: Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead towards neuronal cell death. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset yet later on it worsens. The documented evidence of AD neuropathology manifested the neuro-inflammation, increased reactive oxygen, nitrogen species and decreased antioxidant protective process; mitochondrial dysfunction as well as increased level of acetylcholinesterase activity. Moreover, enhanced action of proteins leads towards neural apoptosis which have a vital role in the degeneration of neurons. The inability of commercial therapeutic options to treat AD with targeting single mechanism leads the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid, latest studies expressed that ellagic acid can initiate the numerous cell signaling transmission and decrease the progression of disorders, involved in the degeneration of neurons. The influential property of ellagic acid to protect the neurons in neurodegenerative disorders is due to its antioxidant effect, iron chelating and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mode of action of ellagic acid against neurodegeneration.

Download Full-text

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

Current Alzheimer Research ◽

10.2174/1567205017666201130085853 ◽

2020 ◽

Vol 17 ◽

Author(s):

Reem Habib Mohamad Ali Ahmad ◽

Marc Fakhoury ◽

Nada Lawand

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

In Vivo Studies ◽

Key Factors ◽

Potential Benefits ◽

Preclinical And Clinical Studies ◽

The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

Download Full-text

Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

Medicinal Chemistry ◽

10.2174/1573406414666181109114214 ◽

2019 ◽

Vol 15 (4) ◽

pp. 373-382 ◽

Cited By ~ 1

Author(s):

Ralph C. Gomes ◽

Renata P. Sakata ◽

Wanda P. Almeida ◽

Fernando Coelho

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Population Aging ◽

Acetylcholinesterase Inhibitors ◽

Acetylcholinesterase Activity ◽

Docking Study ◽

Biological Properties ◽

Ache Inhibitor ◽

Molecular Docking Study

Background: The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease. Methods: The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase. Results: Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Conclusion: We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.

Download Full-text

Study of antioxidant potential in leaves, stems, nuts of Juglans regia L.

International Journal of Bioassays ◽

10.21746/ijbio.2012.10.003 ◽

2012 ◽

Vol 1 (10) ◽

pp. 79 ◽

Cited By ~ 2

Author(s):

G. Raja* ◽

Ivvala Anand Shaker ◽

Inampudi Sailaja ◽

R. Swaminathan ◽

S. Saleem Basha ◽

...

Keyword(s):

Free Radicals ◽

Free Radical ◽

Antioxidant Activities ◽

Radical Scavenging Activity ◽

Juglans Regia ◽

Radical Scavenging ◽

Antioxidant Compounds ◽

Free Radical Damage ◽

Radical Damage

Natural antioxidants can protect the human body from free radicals and retard the progress of many chronic diseases as well as lipid oxidative rancidity in foods. The role of antioxidants has protected effect against free radical damage that may cause many diseases including cancer. Primary sources of naturally occurring antioxidants are known as whole grains, fruits, and vegetables. Several studies suggest that regular consumption of nuts, mostly walnuts, may have beneficial effects against oxidative stress mediated diseases such as cardiovascular disease and cancer. The role of antioxidants has attracted much interest with respect to their protective effect against free radical damage that may cause many diseases including cancer. Juglans regia L. (walnut) contains antioxidant compounds, which are thought to contribute to their biological properties. Polyphenols, flavonoids and flavonols concentrations and antioxidant activity of Leaves, Stems and Nuts extract of Juglans regia L. as evaluated using DPPH, ABTS, Nitric acid, hydroxyl and superoxide radical scavenging activity, lipid peroxidation and total oxidation activity were determined. The antioxidant activities of Leaves, Stems and Nuts extract of Juglans regia L. were concentration dependent in different experimental models and it was observed that free radicals were scavenged by the test compounds in all the models.

Download Full-text

Aß Monomer, Oligomer and Fibril in Alzheimer's Disease

Early Detection and Rehabilitation Technologies for Dementia ◽

10.4018/978-1-60960-559-9.ch016 ◽

2011 ◽

pp. 125-131

Author(s):

Hiroshi Mori

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Senile Plaques ◽

Amyloid Angiopathy ◽

Gamma Secretase ◽

Aged People ◽

Theoretical Predictions ◽

Prevalent Disease

Alzheimer’s disease (AD), the most prevalent disease of aged people, is a progressive neurodegenerative disorder with dementia. Amyloid-ß (also known as ß-protein and referred to here as Aß) is a well-established, seminal peptide in AD that is produced from the amyloid precursor protein (APP) by consecutive digestion with the ß secretase of BACE (beta-site amyloid cleaving enzyme) and gamma secretase of the presenilin complex. Abnormal cerebral accumulation of Abeta in the form of insoluble fibrils in senile plaques and cerebral amyloid angiopathy (CAA) is a neuropathological hallmark of AD. In contrast to insoluble fibrillary Aß, a soluble oligomeric complex, ADDL, consists of low-n oligomers of Aß, such as Aß*56. Despite their different names, it is currently proposed that oligomeric Aß is directly involved in synaptic toxicity and cognitive dysfunction in the early stages of AD. This chapter identifies a novel APP mutation (E693delta; referred to as the Osaka mutation) in a pedigree with probable AD, resulting in a variant Aß lacking glutamate at position 22. Based on theoretical predictions and in vitro studies on synthetic mutant Aß peptides, the mutated Aß peptide showed a unique and enhanced oligomerization activity without fibrillization. This was further confirmed by PiB-PET analysis on the proband patient. Collectively, the chapter concludes that the Osaka mutation is the first human evidence for the hypothesis that oligomeric Aß is involved in AD.

Download Full-text

Domestic Cooking Effects of Bambara Groundnuts and Common Beans in the Antioxidant Properties and Polyphenol Profiles

Journal of Food Research ◽

10.5539/jfr.v6n2p24 ◽

2017 ◽

Vol 6 (2) ◽

pp. 24 ◽

Cited By ~ 4

Author(s):

V. Nyau ◽

S. Prakash ◽

J. Rodrigues ◽

J. Farrant

Keyword(s):

Free Radical ◽

Methanolic Extract ◽

Antioxidant Activities ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Free Radical Scavenging ◽

Esi Ms ◽

Positive Effects ◽

Phytochemical Profiles

Processing of legumes before consumption has several effects on micronutrients, macronutrients and phytonutrients. This study was undertaken to investigate the effect of domestic processing on antioxidant activities and phenolic phytochemicals of the red bambara groundnuts and red beans. The study employed in vitro antioxidant assays (DPPH and FRAP) to screen for antioxidant properties, HPLC-PDA-ESI-MS and Folin Ciocalteu assay to screen for phenolic phytochemical profiles. Domestic cooking displayed positive effects on the antioxidant activity and phenolic phytochemical profiles of the two legumes. The free radical scavenging speed increased 10-fold in the methanolic extract from cooked red bambara groundnuts compared to uncooked. By contrast, the free radical scavenging speed increased 20-fold in the methanolic extract from cooked red beans compared to uncooked. HPLC-PDA-ESI-MS profiles of the cooked red bambara groundnuts and red beans revealed a number of emergent phenolic compounds, mainly flavonoids. These data indicate that cooking appear to enhance the nutraceutical profiles of the legumes investigated.

Download Full-text

ANTIOXIDANT ACTIVITIES OF ROPINIROLE AND PRAMIPEXOLE NOVEL DRUGS USED IN TREATMENT OF PARKINSONISM: AN IN VITRO APPROACH

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9s3.14861 ◽

2016 ◽

Vol 9 (9) ◽

pp. 105 ◽

Cited By ~ 1

Author(s):

Preetha Selva ◽

Srinivasan Vengadassalapathy

Keyword(s):

Free Radical ◽

Dopamine Agonist ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Free Radical Scavenging ◽

Novel Drugs ◽

Dpph Method ◽

Selective Dopamine ◽

Free Radical Scavenging Activities

ABSTRACTObjective: The objective of this study is to evaluate and compare the free radical scavenging activities of selective dopamine agonist namely ropiniroleand pramipexole.Methods: The antioxidant activity of ropinirole and pramipexole at various concentrations was done by 1, 1-diphenyl-2picrylhydrazyl (DPPH) freeradical scavenging assay comparing it with ascorbic acid which was taken as standard.Results: The free radical scavenging property as measured by DPPH method showed that ropinirole and pramipexole have got a potent free radicalscavenging activity with that of ascorbic acid.Conclusion: Novel drugs such as pramipexole and ropinirole are promising molecules in the field of oxidative damage related neurodegenerativedisorders providing us an optimistic targeted approach toward neuroprotection.Keywords: Free radical scavenging, 1, 1-diphenyl-2picrylhydrazyl assay, Anti-Parkinson’s, Dopamine agonist.

Download Full-text

Influence of Woodsmoke Exposure on Molecular Mechanisms Underlying Alzheimer’s Disease: Existing Literature and Gaps in Our Understanding

Epigenetics Insights ◽

10.1177/2516865720954873 ◽

2020 ◽

Vol 13 ◽

pp. 251686572095487

Author(s):

Adam Schuller ◽

Luke Montrose

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Air Pollution ◽

Molecular Mechanisms ◽

Neurodegenerative Disorder ◽

Ambient Air ◽

The United States ◽

Ambient Air Pollution ◽

Current Status

Woodsmoke poses a significant health risk as a growing component of ambient air pollution in the United States. While there is a long history of association between woodsmoke exposure and diseases of the respiratory, circulatory, and cardiovascular systems, recent evidence has linked woodsmoke exposure to cognitive dysfunction, including Alzheimer’s disease dementia. Alzheimer’s disease is a progressive neurodegenerative disorder with largely idiopathic origins and no known cure. Here, we explore the growing body of literature which relates woodsmoke-generated and ambient air pollution particulate matter exposure to Alzheimer’s disease (AD) onset or exacerbation, in the context of an inflammation-centric view of AD. Epigenetic modifications, specifically changes in DNA methylation patterns, are well documented following woodsmoke exposure and have been shown to influence disease-favoring inflammatory cascades, induce oxidative stress, and modulate the immune response in vitro, in vivo, and in humans following exposure to air pollution. Though the current status of the literature does not allow us to draw definitive conclusions linking these events, this review highlights the need for additional work to fill gaps in our understanding of the directionality, causality, and susceptibility throughout the life course.

Download Full-text