scholarly journals Alzheimer’s disease: natural products as inhibitors of neuroinflammation

2020 ◽  
Vol 28 (6) ◽  
pp. 1439-1455
Author(s):  
Olumayokun A. Olajide ◽  
Satyajit D. Sarker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Natural Products ◽  
Molecular Targets ◽  
Limited Success ◽  
Clinical Investigations ◽  
Anti Inflammatory

Abstract Alzheimer’s disease (AD) is the most common form of dementia and affects 44 million people worldwide. New emerging evidence from pre-clinical and clinical investigations shows that neuroinflammation is a major pathological component of AD suggesting that anti-inflammatory strategies are important in delaying the onset or slowing the progression of the disease. However, efforts to employ current anti-inflammatory agents in AD clinical trials have produced limited success. Consequently, there is a need to explore anti-inflammatory natural products, which target neuroinflammatory pathways relevant to AD pathogenesis. This review summarises important druggable molecular targets of neuroinflammation and presents classes of anti-neuroinflammatory natural products with potentials for preventing and reducing symptoms of AD.

Natural Anti-inflammatory compounds as Drug candidates in Alzheimer’s disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Protective Action ◽  
New Drugs ◽  
Huperzine A ◽  
Brain Disorder ◽  
Anti Inflammatory

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

scholarly journals Neuroprotective and Anti-Inflammatory Effects of Low–Moderate Dose Ionizing Radiation in Models of Alzheimer’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3678 ◽  
Author(s):  
Sujin Kim ◽  
Yunkwon Nam ◽  
Chanyang Kim ◽  
Hyewon Lee ◽  
Seojin Hong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Ionizing Radiation ◽  
Pharmacological Intervention ◽  
Therapeutic Effects ◽  
Moderate Dose ◽  
Short Term ◽  
Anti Inflammatory ◽  
5Xfad Mice

Alzheimer’s disease (AD) is the most common cause of dementia. The neuropathological features of AD include amyloid-β (Aβ) deposition and hyperphosphorylated tau accumulation. Although several clinical trials have been conducted to identify a cure for AD, no effective drug or treatment has been identified thus far. Recently, the potential use of non-pharmacological interventions to prevent or treat AD has gained attention. Low-dose ionizing radiation (LDIR) is a non-pharmacological intervention which is currently being evaluated in clinical trials for AD patients. However, the mechanisms underlying the therapeutic effects of LDIR therapy have not yet been established. In this study, we examined the effect of LDIR on Aβ accumulation and Aβ-mediated pathology. To investigate the short-term effects of low–moderate dose ionizing radiation (LMDIR), a total of 9 Gy (1.8 Gy per fraction for five times) were radiated to 4-month-old 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD, and then sacrificed at 4 days after last exposure to LMDIR. Comparing sham-exposed and LMDIR-exposed 5XFAD mice indicated that short-term exposure to LMDIR did not affect Aβ accumulation in the brain, but significantly ameliorated synaptic degeneration, neuronal loss, and neuroinflammation in the hippocampal formation and cerebral cortex. In addition, a direct neuroprotective effect was confirmed in SH-SY5Y neuronal cells treated with Aβ1–42 (2 μM) after single irradiation (1 Gy). In BV-2 microglial cells exposed to Aβ and/or LMDIR, LMDIR therapy significantly inhibited the production of pro-inflammatory molecules and activation of the nuclear factor-kappa B (NF-κB) pathway. These results indicate that LMDIR directly ameliorated neurodegeneration and neuroinflammation in vivo and in vitro. Collectively, our findings suggest that the therapeutic benefits of LMDIR in AD may be mediated by its neuroprotective and anti-inflammatory effects.

Natural product for the treatment of Alzheimer’s disease

2017 ◽  
Vol 28 (5) ◽  
Author(s):  
Thanh Tung Bui ◽  
Thanh Hai Nguyen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Cognitive Function ◽  
Medicinal Plants ◽  
Neurodegenerative Disease ◽  
Natural Product ◽  
Natural Compound ◽  
Anti Inflammatory

AbstractAlzheimer’s disease (AD) is related to increasing age. It is mainly characterized by progressive neurodegenerative disease, which damages memory and cognitive function. Natural products offer many options to reduce the progress and symptoms of many kinds of diseases, including AD. Meanwhile, natural compound structures, including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, have anti-inflammatory, antioxidant, anti-amyloidogenic, and anticholinesterase activities. In this review, we summarize the pathogenesis and targets for treatment of AD. We also present several medicinal plants and isolated compounds that are used for preventing and reducing symptoms of AD.

scholarly journals Anti-inflammatories in Alzheimer’s disease—potential therapy or spurious correlate?

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Jack Rivers-Auty ◽  
Alison E Mather ◽  
Ruth Peters ◽  
Catherine B Lawrence ◽  
David Brough
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Decline ◽  
Negative Binomial ◽  
Drug Efficacy ◽  
Therapeutic Effects ◽  
Inflammatory Drug ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Abstract Epidemiological evidence suggests non-steroidal anti-inflammatory drugs reduce the risk of Alzheimer’s disease. However, clinical trials have found no evidence of non-steroidal anti-inflammatory drug efficacy. This incongruence may be due to the wrong non-steroidal anti-inflammatory drugs being tested in robust clinical trials or the epidemiological findings being caused by confounding factors. Therefore, this study used logistic regression and the innovative approach of negative binomial generalized linear mixed modelling to investigate both prevalence and cognitive decline, respectively, in the Alzheimer’s Disease Neuroimaging dataset for each commonly used non-steroidal anti-inflammatory drug and paracetamol. Use of most non-steroidal anti-inflammatories was associated with reduced Alzheimer’s disease prevalence yet no effect on cognitive decline was observed. Paracetamol had a similar effect on prevalence to these non-steroidal anti-inflammatory drugs suggesting this association is independent of the anti-inflammatory effects and that previous results may be due to spurious associations. Interestingly, diclofenac use was significantly associated with both reduce incidence and slower cognitive decline warranting further research into the potential therapeutic effects of diclofenac in Alzheimer’s disease.

scholarly journals Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer’s Disease

2020 ◽  
Vol 13 (9) ◽  
pp. 242
Author(s):  
Márcia Martins ◽  
Renata Silva ◽  
Madalena M. M. Pinto ◽  
Emília Sousa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Natural Products ◽  
Marine Natural Products ◽  
Biological Activities ◽  
Drug Repurposing ◽  
Phase Iii ◽  
Pharmacological Agents ◽  
Chemical Structures

Alzheimer’s disease (AD) is a multifactorial disease characterized by the presence of amyloid plaques, neurofibrillary tangles, and nerve cell death that affects, mainly, older people. After decades of investigation, the search for an efficacious treatment for AD remains and several strategies can be and are being employed in this journey. In this review, four of the most promising strategies, alongside with its most promising agents under investigation or development are highlighted. Marine natural products (MNP) are a source of unique chemical structures with useful biological activities for AD treatment. One of the most promising compounds, a marine-derived acidic oligosaccharide (GV-971) just passed phase III clinical trials with a unique mechanism of action. Combination therapy and multitargeted-directed ligand therapy (MTDL) are also two important strategies, with several examples in clinical trials, based on the belief that the best approach for AD is a therapy capable of modulating multiple target pathways. Drug repurposing, a strategy that requires a smaller investment and is less time consuming, is emerging as a strong contender with a variety of pharmacological agents resurfacing in an attempt to identify a therapeutic candidate capable of modifying the course of this disease.

Therapeutic implications of anti-inflammatory natural products in Alzheimer’s disease

2019 ◽  
pp. 241-258 ◽  
Author(s):  
Satarupa Deb ◽  
Muhammed Khairujjaman Mazumder ◽  
Ankumoni Dutta ◽  
Banashree Chetia Phukan ◽  
Pallab Bhattacharya ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Therapeutic Implications ◽  
Anti Inflammatory

scholarly journals Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Izumi Maezawa ◽  
David Paul Jenkins ◽  
Benjamin E. Jin ◽  
Heike Wulff
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Brain Injuries ◽  
Potential Therapeutic Target ◽  
Neuroprotective Effects ◽  
Anti Inflammatory ◽  
Calcium Activated Potassium Channel ◽  
The Brain ◽  
Phagocytosis Activity

There exists an urgent need for new target discovery to treat Alzheimer’s disease (AD); however, recent clinical trials based on anti-Aβand anti-inflammatory strategies have yielded disappointing results. To expedite new drug discovery, we propose reposition targets which have been previously pursued by both industry and academia for indications other than AD. One such target is the calcium-activated potassium channel KCa3.1 (KCNN4), which in the brain is primarily expressed in microglia and is significantly upregulated when microglia are activated. We here review the existing evidence supporting that KCa3.1 inhibition could block microglial neurotoxicity without affecting their neuroprotective phagocytosis activity and without being broadly immunosuppressive. The anti-inflammatory and neuroprotective effects of KCa3.1 blockade would be suitable for treating AD as well as cerebrovascular and traumatic brain injuries, two well-known risk factors contributing to the dementia in AD patients presenting with mixed pathologies. Importantly, the pharmacokinetics and pharmacodynamics of several KCa3.1 blockers are well known, and a KCa3.1 blocker has been proven safe in clinical trials. It is therefore promising to reposition old or new KCa3.1 blockers for AD preclinical and clinical trials.

Phytotherapeutics Against Alzheimer’s Disease: Mechanism, Molecular Targets and Challenges for Drug Development

2021 ◽  
Vol 20 ◽  
Author(s):  
Gayathri S ◽  
Raghu Chandrashekar H ◽  
Fayaz S M
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Medicinal Plants ◽  
Herbal Medicines ◽  
Molecular Targets ◽  
Holistic Approach ◽  
Tinospora Cordifolia ◽  
Acorus Calamus ◽  
Approved Drugs

: Alzheimer's disease is inflating worldwide and is combatted by only a few approved drugs. At best, these drugs treat symptomatic conditions by targeting cholinesterase and N-methyl-D-aspartate receptors. Most of the clinical trials in progress are focused to develop disease-modifying agents that aim single targets. The ‘one drug-one target’ approach is failing in the case of Alzheimer’s disease due to its labyrinth etiopathogenesis. Traditional medicinal systems like ayurveda uses a holistic approach encompassing legion of medicinal plants exhibiting multimodal activity. Recent advances in high-throughput technologies have catapulted the research in the arena of ayurveda, specifically in identifying plants with potent anti-Alzheimer’s disease properties and their phytochemical characterization. Nonetheless, clinical trials of very few herbal medicines are in progress. This review is a compendium of Indian plants and ayurvedic medicines against Alzheimer’s disease and their paraphernalia. A record of 230 plants that are found in India with anti-Alzheimer’s disease potential and about 500 phytochemicals from medicinal plants has been solicited with the hope of exploring the unexplored. Further, the molecular targets of phytochemicals isolated from commonly used medicinal plants such as Acorus calamus, Bacopa monnieri, Convolvulus pluricaulis, Tinospora cordifolia and Withania somnifera have been reviewed with respect to their multidimensional property such as antioxidant, anti-inflammation, anti-aggregation, synaptic plasticity modulation, cognition and memory enhancing activity. In addition, the strengths, and challenges in ayurvedic medicine that limit its use as mainstream therapy is discussed and a framework for the development of herbal medicine has been proposed.

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