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Exploring the Therapeutic Potential of Phytochemicals in Alzheimer's Disease: Focus on Polyphenols and Monoterpenes.
Piccialli, I, Tedeschi, V, Caputo, L, D'Errico, S, Ciccone, R, De Feo, V, Secondo, A, Pannaccione, A
Frontiers in pharmacology. 2022;13:876614
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Alzheimer’s disease (AD) is a complex chronic neurodegenerative disorder characterized by the irreversible loss of memory and brain functions. Many different hypotheses are circulating to explain the underlying cause of the disease, yet therapeutic strategies to treat the degenerative processes have been unsuccessful to date. In recent years research has broadened its focus, viewing the pathology of AD more as an interplay of many factors whilst also taking into account other comorbidities associated with AD, such as insulin resistance and low energy production in the brain. One of the big challenges for clinical treatment is that by the time symptoms present and the diagnosis is made, irreversible brain loss has already occurred. Many lifestyle interventions can influence the modifiable risk factors of ageing and hence present a promising preventative strategy for AD. Plant-derived compounds found in foods and medicinal herbs have received much interest due to their versatile action potential. This review specifically looked at compounds in the polyphenols and monoterpenes category and summarized the current evidence, possible mechanisms of action and how this could aid AD management. An overview of the various hypothesis believed to contribute to the development of AD is presented. These include Aβ aggregation and toxicity, Tau hyperphosphorylation and toxicity, oxidative stress and mitochondrial dysfunction, neuroinflammation and brain insulin resistance. A synopsis of the current state of treatments and treatment development is provided, before exploring the potential of plant-derived compounds, in particular polyphenols and monoterpenes and their potential from various sources. Concluding remarks discuss the challenges that come with turning plant-derived compounds into drug treatments. Many studies on mechanisms of action show therapeutic potential, clinical trials in humans have not yet managed to mirror those effects sufficiently. There is a need to advance the field further and assess more thoroughly the clinical relevance of these findings. This review yields a comprehensive and detailed summary of aspects of AD, the proposed mechanisms and the potential of some nutrition related management options.
Abstract
Alzheimer's disease (AD) is a chronic, complex neurodegenerative disorder mainly characterized by the irreversible loss of memory and cognitive functions. Different hypotheses have been proposed thus far to explain the etiology of this devastating disorder, including those centered on the Amyloid-β (Aβ) peptide aggregation, Tau hyperphosphorylation, neuroinflammation and oxidative stress. Nonetheless, the therapeutic strategies conceived thus far to treat AD neurodegeneration have proven unsuccessful, probably due to the use of single-target drugs unable to arrest the progressive deterioration of brain functions. For this reason, the theoretical description of the AD etiology has recently switched from over-emphasizing a single deleterious process to considering AD neurodegeneration as the result of different pathogenic mechanisms and their interplay. Moreover, much relevance has recently been conferred to several comorbidities inducing insulin resistance and brain energy hypometabolism, including diabetes and obesity. As consequence, much interest is currently accorded in AD treatment to a multi-target approach interfering with different pathways at the same time, and to life-style interventions aimed at preventing the modifiable risk-factors strictly associated with aging. In this context, phytochemical compounds are emerging as an enormous source to draw on in the search for multi-target agents completing or assisting the traditional pharmacological medicine. Intriguingly, many plant-derived compounds have proven their efficacy in counteracting several pathogenic processes such as the Aβ aggregation, neuroinflammation, oxidative stress and insulin resistance. Many strategies have also been conceived to overcome the limitations of some promising phytochemicals related to their poor pharmacokinetic profiles, including nanotechnology and synthetic routes. Considering the emerging therapeutic potential of natural medicine, the aim of the present review is therefore to highlight the most promising phytochemical compounds belonging to two major classes, polyphenols and monoterpenes, and to report the main findings about their mechanisms of action relating to the AD pathogenesis.
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Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer's Disease: A Systematic Review.
Gruendler, R, Hippe, B, Sendula Jengic, V, Peterlin, B, Haslberger, AG
Molecules (Basel, Switzerland). 2020;25(24)
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Ageing and the emergence of age-associated illnesses are currently one of the main health challenges in our society. Alzheimer’s disease (AD) is closely associated with ageing and is characterized by progressive memory loss and severe dementia. Currently, there are no therapy options available that halt the progression of the disease. Despite the condition being known for decades, the definitive causes and pathways of the disease and its development are not fully understood. Many drug developments that target some of the known aspects of the disease have failed in the clinical stages, and for nearly 20 years, no new drugs have met FDA approval for the treatment of AD. As increasing evidence suggests diet is an influencing risk factor for AD, the concept of exploring cost-effective, food-derived novel substances with low adverse effects has become more attractive. The first part of this work discusses AD, the prevalence of cognitive decline, limitations of current therapies, the three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and the potential role of food derived substances (nutraceuticals). The second part introduces three nutraceuticals of interest, being epigallocatechin gallate, fisetin, and spermidine. All three compounds have captured scientific interest in regards to aspects of longevity over the recent years. In detail are discussed the current evidence of these compounds concerning autophagy, neuroinflammation, and senescence. This article yields a comprehensive summary of the current evidence from epigallocatechin gallate, fisetin, and spermidine and their potential role in the clinical management of AD.
Abstract
Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer's disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called "nutraceuticals" epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD.
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Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption.
Rothenberg, DO, Zhang, L
Nutrients. 2019;11(6)
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Previous research suggests that tea consumption is linked to a lower risk of depression, but it is not understood why. This meta-analysis and literature review looked at previous human, animal and laboratory studies that might give an indication of the mechanisms by which drinking tea can lead to a reduced depression risk. Tea contains many different active compounds such as L-theanine, various polyphenols and polyphenol metabolites that have effects on the immune system, stress response, brain neurotransmitters such as serotonin and dopamine, and gut bacteria. Different types of tea such as black, green or oolong tea contain different amounts of active compounds. The authors found that these compounds are capable of functioning through multiple pathways simultaneously that together reduce the risk of depression. The authors concluded that daily consumption of moderate amounts of different types of tea may offer significant potential benefit in the risk reduction of depression.
Abstract
This article is a comprehensive review of the literature pertaining to the antidepressant effects and mechanisms of regular tea consumption. Meta-data supplemented with recent observational studies were first analyzed to assess the association between tea consumption and depression risk. The literature reported risk ratios (RR) were 0.69 with 95% confidence intervals of 0.62-0.77. Next, we thoroughly reviewed human trials, mouse models, and in vitro experiments to determine the predominant mechanisms underlying the observed linear relationship between tea consumption and reduced risk of depression. Current theories on the neurobiology of depression were utilized to map tea-mediated mechanisms of antidepressant activity onto an integrated framework of depression pathology. The major nodes within the network framework of depression included hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, inflammation, weakened monoaminergic systems, reduced neurogenesis/neuroplasticity, and poor microbiome diversity affecting the gut-brain axis. We detailed how each node has subsystems within them, including signaling pathways, specific target proteins, or transporters that interface with compounds in tea, mediating their antidepressant effects. A major pathway was found to be the ERK/CREB/BDNF signaling pathway, up-regulated by a number of compounds in tea including teasaponin, L-theanine, EGCG and combinations of tea catechins and their metabolites. Black tea theaflavins and EGCG are potent anti-inflammatory agents via down-regulation of NF-κB signaling. Multiple compounds in tea are effective modulators of dopaminergic activity and the gut-brain axis. Taken together, our findings show that constituents found in all major tea types, predominantly L-theanine, polyphenols and polyphenol metabolites, are capable of functioning through multiple pathways simultaneously to collectively reduce the risk of depression.