The Neuroprotective Potentiality of Flavonoids on Alzheimer’s Disease

Calderaro, Antonella; Patanè, Giuseppe Tancredi; Tellone, Ester; Barreca, Davide; Ficarra, Silvana; Misiti, Francesco; Laganà, Giuseppina

doi:10.3390/ijms232314835

Cited by 63 publications

(37 citation statements)

References 219 publications

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“…Psychedelics can produce sustained therapeutic benefit following a single administration, and also have broad therapeutic value and efficacy in the treatment of disorders, such as depression, post-traumatic stress, anxiety disorders, and addictive substance and alcohol abuse disorders [ 11 ]. A number of flavonoids have been identified with an ability to regulate neural functional properties of potential therapeutic value in the treatment of neurological disorders [ 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. One class of flavonoid metabolite (urolithins) shows particular promise in the treatment of neurodegenerative disorders and in the provision of general health and wellbeing [ 20 , 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

Melrose

2023

Antioxidants

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Flavonoids are a biodiverse family of dietary compounds that have antioxidant, anti-inflammatory, antiviral, and antibacterial cell protective profiles. They have received considerable attention as potential therapeutic agents in biomedicine and have been widely used in traditional complimentary medicine for generations. Such complimentary medical herbal formulations are extremely complex mixtures of many pharmacologically active compounds that provide a therapeutic outcome through a network pharmacological effects of considerable complexity. Methods are emerging to determine the active components used in complimentary medicine and their therapeutic targets and to decipher the complexities of how network pharmacology provides such therapeutic effects. The gut microbiome has important roles to play in the generation of bioactive flavonoid metabolites retaining or exceeding the antioxidative and anti-inflammatory properties of the intact flavonoid and, in some cases, new antitumor and antineurodegenerative bioactivities. Certain food items have been identified with high prebiotic profiles suggesting that neutraceutical supplementation may be beneficially employed to preserve a healthy population of bacterial symbiont species and minimize the establishment of harmful pathogenic organisms. Gut health is an important consideration effecting the overall health and wellbeing of linked organ systems. Bioconversion of dietary flavonoid components in the gut generates therapeutic metabolites that can also be transported by the vagus nerve and systemic circulation to brain cell populations to exert a beneficial effect. This is particularly important in a number of neurological disorders (autism, bipolar disorder, AD, PD) characterized by effects on moods, resulting in depression and anxiety, impaired motor function, and long-term cognitive decline. Native flavonoids have many beneficial properties in the alleviation of inflammation in tissues, however, concerns have been raised that therapeutic levels of flavonoids may not be achieved, thus allowing them to display optimal therapeutic effects. Dietary manipulation and vagal stimulation have both yielded beneficial responses in the treatment of autism spectrum disorders, depression, and anxiety, establishing the vagal nerve as a route of communication in the gut-brain axis with established roles in disease intervention. While a number of native flavonoids are beneficial in the treatment of neurological disorders and are known to penetrate the blood–brain barrier, microbiome-generated flavonoid metabolites (e.g., protocatechuic acid, urolithins, γ-valerolactones), which retain the antioxidant and anti-inflammatory potency of the native flavonoid in addition to bioactive properties that promote mitochondrial health and cerebrovascular microcapillary function, should also be considered as potential biotherapeutic agents. Studies are warranted to experimentally examine the efficacy of flavonoid metabolites directly, as they emerge as novel therapeutic options.

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Section: Introductionmentioning

confidence: 99%

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

Melrose

2023

Antioxidants

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“…Dubois et al, 2019 [ 72 ] showed that AKT3 modulates protection against demyelinating inflammatory disorder. Nutraceutical intervention of the PI3K-AKT pathway in microglial regulation may be promising to consider [ 78 ]. EGCG downregulation of AKT3 may utilize an anti-aging function that mediates AKT3 activity.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

et al. 2023

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Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer’s. Microglia are the brain’s primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds with anti-inflammatory and antioxidant properties, such as epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related neurodegenerative diseases involving activated microglia cells. The objective of the current study was to examine the molecular targets underlying the anti-inflammatory effects of EGCG in activated microglia cells. BV-2 microglia cells were grown, stimulated, and treated with EGCG. Cytotoxicity and nitric oxide (NO) production were evaluated. Immunoassay, PCR array, and WES™ Technology were utilized to evaluate inflammatory, neuroprotective modulators as well as signaling pathways involved in the mechanistic action of neuroinflammation. Our findings showed that EGCG significantly inhibited proinflammatory mediator NO production in LPS-stimulated BV-2 microglia cells. In addition, ELISA analysis revealed that EGCG significantly decreases the release of proinflammatory cytokine IL-6 while it increases the release of TNF-α. PCR array analysis showed that EGCG downregulated MIF, CCL-2, and CSF2. It also upregulated IL-3, IL-11, and TNFS10. Furthermore, the analysis of inflammatory signaling pathways showed that EGCG significantly downregulated mRNA expression of mTOR, NF-κB2, STAT1, Akt3, CCL5, and SMAD3 while significantly upregulating the expression of mRNA of Ins2, Pld2, A20/TNFAIP3, and GAB1. Additionally, EGCG reduced the relative protein expression of NF-κB2, mTOR, and Akt3. These findings suggest that EGCG may be used for its anti-inflammatory effects to prevent neurodegenerative diseases.

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Section: Othersmentioning

confidence: 99%

“…Unfortunately, there is still a lack of clinical evidence for these promising flavonoids. We discovered a clinical study that began in 2022 and will end in 2024 to determine the efficacy and safety of cotton flavonoid tablets for the treatment of AD (Calderaro et al, 2022). Although the exact mechanisms of action are unclear, several important physiological responses regulated by flavonoids may be key to promoting the neuroprotective effect of AD.…”

Section: Anti‐ad Active Ingredients In Plantsmentioning

confidence: 99%

Update on new trends and progress of natural active ingredients in the intervention of Alzheimer's disease, based on understanding of traditional Chinese and Western relevant theories: A review

Rang

Liu

et al. 2023

Phytotherapy Research

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Alzheimer's disease (AD) is one of the major neurological disorders causing death in the elderly worldwide. As a neurodegenerative disease that is difficult to prevent and cure, the pathogenesis of AD is complex and there is no effective cure. A variety of natural products derived from plants have been reported to have promising anti‐AD activities, including flavonoids, terpenes, phenolic acids and alkaloids, which can effectively relieve the symptoms of AD in a variety of ways. This paper mainly reviews the pharmacological activity and mechanisms of natural products against AD. Although the clinical efficacy of these plants still needs to be determined by further high‐quality studies, it may also provide a basis for future researchers to study anti‐AD in depth.

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The Neuroprotective Potentiality of Flavonoids on Alzheimer’s Disease

Cited by 63 publications

References 219 publications

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

Update on new trends and progress of natural active ingredients in the intervention of Alzheimer's disease, based on understanding of traditional Chinese and Western relevant theories: A review

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