Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Thapa, Arjun; Y., Eva

doi:10.1007/978-3-319-18365-7_3

Cited by 37 publications

(25 citation statements)

References 105 publications

(248 reference statements)

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“…Although the molecular mechanisms remain to be elucidated, flavonoids have been shown to alter the Aβ aggregation pathway to yield non-toxic, unstructured Aβ aggregates, as well as directly exerting a neuroprotective effect to cells. In this chapter, we review biflavonoid-mediated Aβ aggregation and toxicity, and highlight the beneficial roles biflavonoids can potentially play in the prevention and treatment of Alzheimer's disease 93 .…”

Section: Biological Effects Of Polyphenolsmentioning

confidence: 99%

“Polyphenolic-food” Effects on Brain Health (Human Data review)

Stefania¹

2019

BIOMEDJ

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Preventive strategies and nutritional interventions seem to be promising approaches to delay neurocognitive decline and reduce the risk of neurodegenerative diseases. Among the various nutritional protocols, numerous studies confirm: the Mediterranean diet is the best food style to preserve the decay of our brain and live long. The elderly who constantly follow this type of diet would have a brain less "consumed" than those who follow a different food style. But what are the magic molecules present in fruits, vegetables, olive oil, legumes, able to protect us from aging and degenerative phenomena? The polyphenols: phytochemicals that fight cellular aging by counteracting the action of free radicals. These substances are able to stimulate cell repair systems, to amplify the endogenous antioxidant defenses, to specifically inhibit the action of inflammatory molecules. The trigger of this defensive response is linked to the peculiar ability of the polyphenols to modulate specific signaling mechanisms and transcription factors. Here we review the role of some "polyphenolic-food" of Mediterranean diet for the maintenance of cognitive performance, focusing specifically on human studies and the beneficial effects associated with overall diet composition, rather than single nutrient supplementations, for the prevention or the delay of neurodegenerative diseases.

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Section: Biological Effects Of Polyphenolsmentioning

confidence: 99%

“Polyphenolic-food” Effects on Brain Health (Human Data review)

Stefania¹

2019

BIOMEDJ

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“…Moreover, phagocytosis processes generate significant amounts of ROS in cells. Pro-inflammatory cytokines, such as interluekin-1 and interferon-γ also produce large amounts of reactive nitric oxide by inducing nitric oxide synthase (iNOS) [ 6 , 24 , 27 , 28 , 29 ].…”

Section: Oxidative Stress and Aging Related Diseasesmentioning

confidence: 99%

“…The mechanisms of AD are largely unknown. Inflammation, intracellular calcium ion release, autophagy, apoptosis, and, importantly, over production and aggregation (crosslinking) of Aβ peptides are widely believed to be involved in AD neurodegeneration [ 6 , 29 , 32 , 33 , 35 , 36 ]. Neuronal cells, among others, are particularly susceptible to oxidative stress induced degenerations [ 17 , 18 ].…”

Section: Oxidative Stress and Alzheimer’s Diseasementioning

confidence: 99%

“…Compared to other cells, neurons comprise a low level of anti-oxidant defense molecules such as glutathione (GSH), and contain a higher amount of oxidation prone polyunsaturated fatty acids [ 1 , 29 , 37 ]. The presence of anti-oxidative enzymes, hemeoxygenase (OH)-1 and superoxide dismutase (SOD)-1 in senile plaques clearly indicate the involvement of oxidative stress in AD pathology [ 1 , 29 , 38 ]. Importantly, oxidative stress has been reported to be a relatively early event in AD pathogenesis [ 39 ].…”

Section: Oxidative Stress and Alzheimer’s Diseasementioning

confidence: 99%

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Dietary Modulation of Oxidative Stress in Alzheimer’s Disease

Thapa

Carroll

2017

IJMS

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Cells generate unpaired electrons, typically via oxygen- or nitrogen-based by-products during normal cellular respiration and under stressed situations. These pro-oxidant molecules are highly unstable and may oxidize surrounding cellular macromolecules. Under normal conditions, the reactive oxygen or nitrogen species can be beneficial to cell survival and function by destroying and degrading pathogens or antigens. However, excessive generation and accumulation of the reactive pro-oxidant species over time can damage proteins, lipids, carbohydrates, and nucleic acids. Over time, this oxidative stress can contribute to a range of aging-related degenerative diseases such as cancer, diabetes, macular degeneration, and Alzheimer’s, and Parkinson’s diseases. It is well accepted that natural compounds, including vitamins A, C, and E, β-carotene, and minerals found in fruits and vegetables are powerful anti-oxidants that offer health benefits against several different oxidative stress induced degenerative diseases, including Alzheimer’s disease (AD). There is increasing interest in developing anti-oxidative therapeutics to prevent AD. There are contradictory and inconsistent reports on the possible benefits of anti-oxidative supplements; however, fruits and vegetables enriched with multiple anti-oxidants (e.g., flavonoids and polyphenols) and minerals may be highly effective in attenuating the harmful effects of oxidative stress. As the physiological activation of either protective or destructive pro-oxidant behavior remains relatively unclear, it is not straightforward to relate the efficacy of dietary anti-oxidants in disease prevention. Here, we review oxidative stress mediated toxicity associated with AD and highlight the modulatory roles of natural dietary anti-oxidants in preventing AD.

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“…A great number of natural compounds have shown powerful anti-Aβ effects through multiple actions mentioned above. [11][12][13][14][15] Notably, curcumin and its related compounds, a group of natural diarylheptanoids found in the spice turmeric of the ginger family (Zingiberaceae), have long gained attention for their abilities of Aβ aggregation/signaling antagonism and memory enhancement. [16][17][18][19][20] Resveratrol, a natural polyphenolic compound found in many plants, is demonstrated to have multi-neuroprotective effects against Aβ toxicity.…”

Section: -3)mentioning

confidence: 99%

7-(4-Hydroxyphenyl)-1-phenyl-4<i>E</i>-hepten-3-one, a Diarylheptanoid from <i>Alpinia officinarum</i>, Protects Neurons against Amyloid-β Induced Toxicity

Huang

Tang

Liao

et al. 2016

Biological & Pharmaceutical Bulletin

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Amyloid-β (Aβ) is one of the major causative agents of Alzheimer's disease (AD), the most common neurodegenerative disorder characterized by progressive cognitive impairment. While effective drugs for AD are currently limited, identifying anti-Aβ compounds from natural products has been shown as a promising strategy which may lead to breakthroughs for new drug candidate discovery. We have previously reported that 7-(4-hydroxyphenyl)-1-phenyl-4E-hepten-3-one (AO-1), a diarylheptanoid extracted from the plant Alpinia officinarum, has strong effects on neuronal differentiation and neurite outgrowth in vitro and in vivo. The present study further uncovers that AO-1 exerts neuroprotective effects against the neurotoxicity caused by Aβ. Under the damage of Aβ oligomers, the major pathological forms of Aβ, dendrites of neurons become atrophic and simplified, but such impairments were substantially alleviated by AO-1 treatment. Moreover, AO-1 reduced apoptotic levels and oxidative stress triggered by Aβ. Further analysis showed that the anticaspase and dendrite protective effects of AO-1 were dependent on activation of phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathways. These findings collectively identify AO-1 as a beneficial compound to ameliorate the deleterious effects of Aβ on dendrite integrity and cell survival, and may provide new insights on drug discovery of AD.Key words Alzheimer's disease (AD); amyloid-β (Aβ); dendrite; mammalian target of rapamycin (mTOR); neuroprotection; phosphatidylinositol 3-kinase (PI3K) Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the elderly which is characterized by progressive cognitive decline and movement dysfunction. Being a disease with extremely complex etiology, the accumulation of amyloid-β (Aβ) peptides is believed as a main pathogenic event that directly causes neurodegeneration. 1-3)Aβ peptides, which are normally constituted by 40-42 amino acids, are released by the aberrant cleavage of amyloid precursor protein (APP) and deposit at synapses. Aβ peptides are the major component of the senile plaques observed in AD brain. Moreover, soluble oligomers formed by aggregation of monomeric Aβ42 (1-42 a.a.) peptides are the most pathogenic forms during early progression of AD. The damaging effects of Aβ42 includes synapse loss, neurite dystrophy and dendritic simplification.4,5) Thus, one of the current efforts for drug development against AD is to generate platforms that aim at antagonizing the devastating effects of Aβ oligomers. Such approaches have been proven promising for therapeutic design and drug discovery of AD. [6][7][8] A variety of compounds derived from natural sources have been identified effective for counteracting Aβ-induced neurotoxicity.9,10) Such anti-Aβ activities could be achieved through several ways. For instance, Aβ production or aggregation is prevented, or Aβ clearance is accelerated. Moreover, Aβ-induced signaling pathways could be blocked or downregulated. A great number of natural compou...

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Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Cited by 37 publications

References 105 publications

“Polyphenolic-food” Effects on Brain Health (Human Data review)

“Polyphenolic-food” Effects on Brain Health (Human Data review)

Dietary Modulation of Oxidative Stress in Alzheimer’s Disease

7-(4-Hydroxyphenyl)-1-phenyl-4<i>E</i>-hepten-3-one, a Diarylheptanoid from <i>Alpinia officinarum</i>, Protects Neurons against Amyloid-β Induced Toxicity

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