Indole-3 Carbinol and Diindolylmethane Mitigated β-Amyloid-Induced Neurotoxicity and Acetylcholinesterase Enzyme Activity: In Silico, In Vitro, and Network Pharmacology Study

Diseases, Journal Year: 2024, Volume and Issue: 12(8), P. 184 - 184

Published: Aug. 16, 2024

Background: Alzheimer’s disease (AD) is a neurodegenerative characterized by beta-amyloid (Aβ) deposition and increased acetylcholinesterase (AchE) enzyme activities. Indole 3 carbinol (I3C) diindolylmethane (DIM) are reported to have neuroprotective activities against various neurological diseases, including ischemic stroke, Parkinson’s disease, neonatal asphyxia, depression, stress, neuroinflammation, excitotoxicity, except for AD. In the present study, we investigated anti-AD effects of I3C DIM. Methods: Docking molecular dynamic studies AchE network pharmacological were conducted DIM’s self AchE-induced Aβ aggregation investigated. The DIM Aβ-induced neurotoxicity assessed in SH-S5Y5 cells observing cell viability ROS. Results: with show binding efficiency −7.0 −10.3, respectively, dynamics revealed better interaction stability between AchE. Network indicated that interacted several proteins involved pathophysiology Further, significantly inhibited (IC50: (18.98 µM) (11.84 µM)) self-induced aggregation. Both compounds enhanced exposed reduced equipotential neuroprotection when compared donepezil. Conclusions: Our findings indicate both inhibiting induced

Language: Английский

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Exosomes as therapeutic and drug delivery vehicle for neurodegenerative diseases

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 2, 2024

Abstract Neurodegenerative disorders are complex, progressive, and life-threatening. They cause mortality disability for millions of people worldwide. Appropriate treatment neurodegenerative diseases (NDs) is still clinically lacking due to the presence blood-brain barrier (BBB). Developing an effective transport system that can cross BBB enhance therapeutic effect neuroprotective agents has been a major challenge NDs. Exosomes endogenous nano-sized vesicles naturally carry biomolecular cargoes. Many studies have indicated exosome content, particularly microRNAs (miRNAs), possess biological activities by targeting several signaling pathways involved in apoptosis, inflammation, autophagy, oxidative stress. Exosome content influence cellular function healthy or pathological ways. Furthermore, since exosomes reflect features parental cells, their cargoes offer opportunities early diagnosis intervention diseases. unique characteristics make them ideal delivering drugs directly brain. These include ability pass through BBB, biocompatibility, stability, innate properties. This review emphasizes role alleviating NDs discusses associated molecular mechanisms. exosomes, making promising natural transporter various medications brain combat NDs, also discussed.

Language: Английский

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Polyphenols, Alkaloids, and Terpenoids Against Neurodegeneration: Evaluating the Neuroprotective Effects of Phytocompounds Through a Comprehensive Review of the Current Evidence

Metabolites, Journal Year: 2025, Volume and Issue: 15(2), P. 124 - 124

Published: Feb. 13, 2025

Neurodegenerative diseases comprise a group of chronic, usually age-related, disorders characterized by progressive neuronal loss, deformation structure, or loss function, leading to substantially reduced quality life. They remain significant focus scientific and clinical interest due their increasing medical social importance. Most neurodegenerative present intracellular protein aggregation extracellular deposition (plaques), such as α-synuclein in Parkinson's disease amyloid beta (Aβ)/tau aggregates Alzheimer's. Conventional treatments for conditions incur high costs are related the development several adverse effects. In addition, many patients irresponsive them. For these reasons, there is growing tendency find new therapeutic approaches help patients. This review intends investigate some phytocompounds' effects on diseases. These generally increased oxidative stress inflammation, so phytocompounds can prevent treat To achieve our aim provide critical assessment current literature about phytochemicals targeting neurodegeneration, we reviewed reputable databases, including PubMed, EMBASE, COCHRANE, seeking trials that utilized against conditions. A few investigated humans, after screening, 13 were ultimately included following PRISMA guidelines. compounds include polyphenols (flavonoids luteolin quercetin, phenolic acids rosmarinic acid, ferulic caffeic other like resveratrol), alkaloids (such berberine, huperzine A, caffeine), terpenoids ginkgolides limonene). The gathered evidence underscores caffeine, ginkgolides, primarily anti-inflammatory, antioxidant, neuroprotective, counteracting neuroinflammation, oxidation, synaptic dysfunctions, which crucial aspects intervention various conditions, Alzheimer's dementias, depression, neuropsychiatric disorders. summary, they show use improvements cognition, memory, disinhibition, irritability/lability, aberrant behavior, hallucinations, mood

Language: Английский

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Targeting uric acid: a promising intervention against oxidative stress and neuroinflammation in neurodegenerative diseases

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 3, 2025

Oxidative stress and neuroinflammation are recognized as key factors in the development of neurodegenerative diseases, yet effective interventions biomarkers to address oxidative these conditions limited. Uric acid (UA), traditionally associated with gout, is now gaining prominence a potential target diseases. Soluble UA stands out one most vital antioxidant compounds produced by human body, accounting for up 55% extracellular capacity neutralize free radicals. While there increasing evidence supporting neuroprotective properties Parkinson's disease Alzheimer's disease, gaps knowledge still exist regarding underlying mechanisms how effectively translate benefits into clinical practice. Moreover, current elevation therapy exhibits unstable properties, individual variability, even adverse effects, limiting its applications. This review consolidates recent advancements understanding exerts effects on diseases emphasizes dual roles managing neuroinflammation. Additionally, elucidates through which confers neuroprotection. Based this, underscores significance biomarker aims provide comprehensive therapeutic target, while also addressing possible challenges implementation.

Language: Английский

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Relationship between enriched environment and neurodegeneration: a review from mechanism to therapy

Clinical Epigenetics, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 24, 2025

Enriched environment (EE), as a non-pharmacological intervention, has garnered considerable attention for its potential to ameliorate neurodegenerative diseases (NDs). This review delineated the impact of EE on biological functions associated with NDs, emphasizing role in enhancing neural plasticity, reducing inflammation, and bolstering cognitive performance. We discussed molecular underpinnings effects EE, including modulation key signaling pathways such extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinases (MAPK), AMPK/SIRT1, which were implicated neuroprotection synaptic plasticity. Additionally, we scrutinized influence epigenetic modifications autophagy, processes pivotal ND pathogenesis. Animal models, encompassing both rodents larger animals, offer insights into disease-modifying underscoring complementary approach pharmacological interventions. In summary, emerges promising strategy augment function decelerate progression NDs.

Language: Английский

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An Update of Fungal Endophyte Diversity and Strategies for Augmenting Therapeutic Potential of their Potent Metabolites: Recent Advancement

Applied Biochemistry and Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Abstract Endophytic fungi represent a significant renewable resource for the discovery of pharmaceutically important compounds, offering substantial potential new drug development. Their ability to address growing issue resistance has drawn attention from researchers seeking novel, nature-derived lead molecules that can be produced on large scale meet global demand. Recent advancements in genomics, metabolomics, bioinformatics, and improved cultivation techniques have significantly aided identification characterization fungal endophytes their metabolites. Current estimates suggest there are approximately 1.20 million globally, yet only around 16% (190,000) been identified studied detail. This underscores vast untapped pharmaceutical research. Research increasingly focused transformation bioactive compounds by through chemical enzymatic processes. A notable example is anthraquinone derivative 6-O-methylalaternin, whose cytotoxic enhanced addition hydroxyl group, sharing structural similarities with its parent compound macrosporin. These structure-bioactivity studies open up avenues developing safer more effective therapeutic agents synthesizing targeted derivatives. Despite immense promise, challenges remain, particularly large-scale understanding complexities biosynthetic pathways. Additionally, genetic manipulation optimized metabolite production still infancy. Future research should aim overcome these limitations focusing efficient methods deeper exploration endophytes’ metabolic capabilities fully harness potential. Graphical

Language: Английский

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Unravelling neuroregenerative and neuroprotective roles of Wnt/β-catenin pathway in ischemic stroke: Insights into molecular mechanisms

Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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A comprehensive review of advanced focused ultrasound (FUS) microbubbles-mediated treatment of Alzheimer’s disease

Heliyon, Journal Year: 2024, Volume and Issue: 10(18), P. e37533 - e37533

Published: Sept. 1, 2024

Language: Английский

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A Self-Emulsifying Nanococktail of Pomegranate and Cannabidiol Reduces Cognitive Decline in Mice

Nutrition and Dietary Supplements, Journal Year: 2025, Volume and Issue: Volume 17, P. 19 - 28

Published: Feb. 1, 2025

Introduction: Stress and inflammation in the early stages of cognitive decline has spurred interest use antioxidants as prophylactic therapeutic agents. Several studies have established neuroprotective capacities a pomegranate oil nano-formulation (Nano-PSO). In parallel, cannabis-derived cannabidiol (CBD) prevented social recognition deficits reduced neuroinflammation mice. This work assessed impact Nano-PSO:CBD on memory learning. Methods: A battery hemp extracts was screened for their effects acetylcholine esterase inhibition neuronal protection activities. The best-performing extract in-vitro assays nano-formulated via self-emulsifying system with PSO administered to aged mice MK-801-induced decline, which were then subjected Morris water maze test Y-maze test, respectively. Results: Aged chronically fed performed 22– 31% shorter escape latency (p ≤ 0.05), 23% distance swam increased average speed compared control Mice pretreated prior MK-801 had significantly higher percentage entries into novel arm untreated controls. Discussion: CBD salutary effect memory, learning spatial should be further studied clinical context. Keywords: cognition, nanoformulation, CBD, seed oil, nano-omega 5, brain protect, punicic acid

Language: Английский

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Heavy metal-induced disruption of the autophagy-lysosomal pathway: implications for aging and neurodegenerative disorders

BioMetals, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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