Neuroprotective Potentials of Flavonoids: Experimental Studies and Mechanisms of Action

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 280 - 280

Published: Jan. 27, 2023

Neurological and neurodegenerative diseases, particularly those related to aging, are on the rise, but drug therapies rarely curative. Functional disorders organic degeneration of nervous tissue often have complex causes, in which phenomena oxidative stress, inflammation cytotoxicity intertwined. For these reasons, search for natural substances that can slow down or counteract pathologies has increased rapidly over last two decades. In this paper, studies neuroprotective effects flavonoids (especially most widely used, hesperidin quercetin) animal models depression, neurotoxicity, Alzheimer’s disease (AD) Parkinson’s reviewed. The literature topics amounts a few hundred publications vitro vivo (notably rodents) provides us with very detailed picture action mechanisms targets substances. These include decrease enzymes produce reactive oxygen ferroptosis, inhibition mono-amine oxidases, stimulation Nrf2/ARE system, induction brain-derived neurotrophic factor production and, case AD, prevention amyloid-beta aggregation. neuroinflammatory processes been documented as cytokine formation (mainly TNF-alpha IL-1beta) by microglia astrocytes, modulating number regulatory proteins such Nf-kB NLRP3/inflammasome. Although clinical trials humans still scarce, preclinical allow consider hesperidin, quercetin, other interesting safe dietary molecules be further investigated complementary treatments order prevent diseases moderate their deleterious effects.

Language: Английский

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Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103032 - 103032

Published: Jan. 21, 2024

Thioredoxin (Trx) is a compact redox-regulatory protein that modulates cellular redox state by reducing oxidized proteins. Trx exhibits dual functionality as an antioxidant and cofactor for diverse enzymes transcription factors, thereby exerting influence over their activity function. has emerged pivotal biomarker various diseases, particularly those associated with oxidative stress, inflammation, aging. Recent clinical investigations have underscored the significance of in disease diagnosis, treatment, mechanistic elucidation. Despite its paramount importance, intricate interplay between senescence-a condition characterized irreversible growth arrest induced multiple aging stimuli-remains inadequately understood. In this review, our objective to present comprehensive up-to-date overview structure function Trx, involvement signaling pathways senescence, association age-related well potential therapeutic target. Our review aims elucidate novel extensive role senescence while highlighting implications diseases.

Language: Английский

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Pharmacological Activity, Pharmacokinetics, and Clinical Research Progress of Puerarin

Antioxidants, Journal Year: 2022, Volume and Issue: 11(11), P. 2121 - 2121

Published: Oct. 27, 2022

As a kind of medicine and food homologous plant, kudzu root (Pueraria lobata (Willd.) Ohwi) is called an “official medicine” in Chinese folk medicine. Puerarin the main active component extracted from root, its structural formula 8-β-D-grapes pyranose-4, 7-dihydroxy isoflavone, with white needle crystal; it slightly soluble water, aqueous solution colorless or light yellow. natural antioxidant high health value has series biological activities such as antioxidation, anti-inflammation, anti-tumor effects, immunity improvement, cardio-cerebrovascular nerve cell protection. In particular, for past few years, also been extensively used clinical study. This review focuses on activity puerarin, therapy diverse types inflammatory diseases, various new drug delivery systems “structure-activity relationship” puerarin derivatives, pharmacokinetic studies, which can provide perspective puerarin-related research development, application, further development utilization.

Language: Английский

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Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 23, 2023

Alzheimer's Disease (AD) is a global chronic disease in adults with beta-amyloid (Aβ) deposits and hyperphosphorylated tau protein as the pathologic characteristics. Although exact etiology of AD still not fully elucidated, aberrant metabolism including insulin signaling mitochondria dysfunction plays an important role development AD. Binding to receptor substrates, can transport through blood-brain barrier (BBB), thus mediating pathways regulate physiological functions. Impaired pathways, PI3K/Akt/GSK3β MAPK could cause damage brain pathogenesis Mitochondrial overexpression TXNIP also be causative links between DM. Some antidiabetic medicines may have benefits treatment Metformin beneficial for cognition improvement patients, although results from clinical trials were inconsistent. Exendin-4 affect animal models but there lack trials. Liraglutide dulaglutide benefit patients adequate studies semaglutide. Dipeptidyl peptidase IV inhibitors (DPP4is) such saxagliptin, vildagliptin, linagliptin, sitagliptin boost cognitive function models. And SGLT2 empagliflozin dapagliflozin considerably protective against new-onset dementia T2DM patients. Insulin therapy promising some indicated that it increase risk Herbal are helpful neuroprotection brain. For example, polyphenols, alkaloids, glycosides, flavonoids glucose metabolism. Focusing on metabolism, we summarized pharmacological mechanism hypoglycemic drugs herbal medicines. New approaches synthesized would provided More needed produce definite evidence effectiveness medications.

Language: Английский

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α-Arrestins and Their Functions: From Yeast to Human Health

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4988 - 4988

Published: April 30, 2022

α-Arrestins, also called arrestin-related trafficking adaptors (ARTs), constitute a large family of proteins conserved from yeast to humans. Despite their evolutionary precedence over extensively studied relatives the β-arrestin family, α-arrestins have been discovered relatively recently, and thus properties are mostly unexplored. The predominant function is selective identification membrane for ubiquitination degradation, which an important element in maintaining protein homeostasis as well global cellular metabolisms. Among members arrestin clan, only possess PY motifs that allow canonical binding WW domains Rsp5/NEDD4 ubiquitin ligases subsequent leading vacuolar/lysosomal degradation. molecular mechanisms substrate's targeting, function, regulation response different stimuli remain incompletely understood. Several functions animal models recently characterized, including redox regulation, innate immune tumor suppression. However, α-arrestin substrate interactions mainly based on observations Saccharomyces cerevisiae model. Nonetheless, implicated health disorders such diabetes, cardiovascular diseases, neurodegenerative disorders, progression, placing them group potential therapeutic targets.

Language: Английский

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Advances in the Functions of Thioredoxin System in Central Nervous System Diseases

Antioxidants and Redox Signaling, Journal Year: 2022, Volume and Issue: unknown

Published: June 28, 2022

Significance: The thioredoxin system comprises (Trx), reductase (TrxR), and nicotinamide adenine dinucleotide phosphate, besides an endogenous Trx inhibitor, the thioredoxin-interacting protein (TXNIP). plays critical roles in maintaining redox homeostasis central nervous (CNS), which oxidative stress damage is prone to occurrence due its high-energy demand. Recent Advances: Increasing studies have demonstrated that expression or activity of Trx/TrxR usually decreased TXNIP increased patients with CNS diseases, including neurodegenerative cerebral ischemia, traumatic brain injury, depression, as well their cellular animal models. compromise enhances susceptibility neurons related pathological state. Increased not only inhibition activity, but also activates NOD-like receptor 3 inflammasome, resulting neuroinflammation brain. Critical Issues: In this review, we highlight sources CNS. function are summarized different diseases. This review mentions some inducers show neuroprotection Future Directions: Accumulating evidence has important suggesting may be a promising therapeutic target for Further study should aim develop most effective specific inhibitors apply them clinical trials treatment Antioxid. Redox Signal. 38, 425-441.

Language: Английский

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Is Drp1 a link between mitochondrial dysfunction and inflammation in Alzheimer’s disease?

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: May 12, 2023

Recent advances highlight that inflammation is critical to Alzheimer Disease (AD) pathogenesis. Indeed, several diseases characterized by are considered risk factors for AD, such as type 2 diabetes, obesity, hypertension, and traumatic brain injury. Moreover, allelic variations in genes involved the inflammatory cascade AD. AD also mitochondrial dysfunction, which affects energy homeostasis of brain. The role dysfunction has been mostly neuronal cells. However, recent data demonstrating occurs cells, promoting secretion pro-inflammatory cytokines, turn induce neurodegeneration. In this review, we summarize finding supporting hypothesis inflammatory-amyloid describe demonstrate link between altered cascade. We focus summarizing Drp1, fission, showing Drp1 activation leads NLRP3 inflammasome, cascade, aggravates Amyloid beta (Ab) deposition tau-induced neurodegeneration, relevance pathway an early event

Language: Английский

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Exosomes Regulate NLRP3 Inflammasome in Diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 3, 2022

Emerging evidence has suggested the unique and critical role of exosomes as signal molecules vector in various diseases. Numerous researchers have been trying to identify how these function immune progression, this could promote their use biomarkers for disease process potential promising diagnostic tools. NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3), a tripartite protein, contains three functional domains central nucleotide-binding oligomerization (NACHT), an N-terminal (PYD), leucine-rich repeat (LRR). Of note, existing studies identified exosome novel mediator NLRP3 inflammasome, which is diseases progression. However, actual mechanisms clinical treatment related are still not fully understood. Herein, we presented up-to-date review diseases, outlining what known about activation inflammasome also highlighting areas topic that warrant further study.

Language: Английский

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27-Hydroxycholesterol impairs learning and memory ability via decreasing brain glucose uptake mediated by the gut microbiota

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115649 - 115649

Published: Oct. 6, 2023

Brain glucose hypometabolism is a significant manifestation of Alzheimer's disease (AD). 27-hydroxycholesterol (27-OHC) and the gut microbiota have been recognized as factors possibly influencing pathogenesis AD. This study aimed to investigate link between 27-OHC, microbiota, brain uptake in Here, 6-month-old male C57BL/6 J mice were treated with sterile water or antibiotic cocktails, without 27-OHC and/or synthetic enzyme CYP27A1 inhibitor anastrozole (ANS). The levels, memory ability measured. We observed that altered composition, damaged tissue structures, decreased 2-deoxy-2-[18 F] fluorodeoxyglucose (18F-FDG) value, downregulated gene expression transporter type 4 (GLUT4), reduced colocalization GLUT1/glial fibrillary acidic protein (GFAP) hippocampus, impaired spatial memory. ANS reversed effects 27-OHC. antibiotic-treated did not exhibit similar results after treatment. reveals potential molecular mechanism wherein 27-OHC-induced impairment might be linked uptake, mediated by microbiota.

Language: Английский

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Luteolin, apigenin, and chrysin inhibit lipotoxicity–induced NLRP3 inflammasome activation and autophagy damage in macrophages by suppressing endoplasmic reticulum stress

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(8), P. 4120 - 4133

Published: April 23, 2024

Lipotoxicity leads to numerous metabolic disorders such as nonalcoholic steatohepatitis. Luteolin, apigenin, and chrysin are three flavones with known antioxidant anti-inflammatory properties, but whether they inhibit lipotoxicity-mediated NLRP3 inflammasome activation was unclear. To address this question, we used J774A.1 macrophages Kupffer cells stimulated 100 μM palmitate (PA) in the presence or absence of 20 each flavone. PA increased p-PERK, p-IRE1α, p-JNK1/2, CHOP, TXNIP well p62 LC3-II expression induced autophagic flux damage. Caspase-1 IL-1β release were also noted after 24 h exposure PA. In PERK inhibitor GSK2656157, PA-induced CHOP caspase-1 mitigated. Compared treatment alone, Bcl-2 coupled beclin-1 elevated autophagy reversed by JNK SP600125. With luteolin, treatment, ROS production, ER stress, expression, damage, apoptosis ameliorated. Moreover, binding response LPS/PA challenge reduced. These results suggest that protect hepatic against damage attenuating endoplasmic reticulum stress.

Language: Английский

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