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

Metabolites, Год журнала: 2025, Номер 15(2), С. 124 - 124

Опубликована: Фев. 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

Язык: Английский

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Copper Imparts a New Therapeutic Property to Resveratrol by Generating ROS to Deactivate Cell-Free Chromatin

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 132 - 132

Опубликована: Янв. 20, 2025

Resveratrol, a bioactive phytoalexin, has been extensively studied as pharmaceutical and nutraceutical candidate for the treatment of various diseases. Although its therapeutic effects have largely attributed to anti-oxidant properties, underlying mechanisms dose dependency are not well understood. Recent studies shown that cell-free chromatin particles (cfChPs), which released daily from billions dying cells, can enter circulation be internalized by healthy wherein they trigger damaging effects, including double-strand DNA breaks. Notably, deactivating cfChPs using mixture resveratrol copper neutralize their harmful effects. The addition imparts novel property viz. generation reactive oxygen species (ROS), capable without genomic DNA. This perspective article discusses how deactivation via ROS generated combining with multiple Exploiting deactivate ameliorate disease conditions may viable approach.

Язык: Английский

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Mechanisms and Potential Benefits of Neuroprotective Agents in Neurological Health

Nutrients, Год журнала: 2024, Номер 16(24), С. 4368 - 4368

Опубликована: Дек. 18, 2024

The brain contains many interconnected and complex cellular molecular mechanisms. Injury to the causes permanent dysfunctions in these So, it continues be an area where surgical intervention cannot performed except for removal of tumors repair some aneurysms. Some agents that can cross blood–brain barrier reach neurons show neuroprotective effects due their anti-apoptotic, anti-inflammatory antioxidant properties. In particular, act by reducing or modulating accumulation protein aggregates neurodegenerative diseases (Alzheimer’s disease, Parkinson’s Huntington’s Amyotrophic lateral sclerosis, prion disease) caused accumulation. Substrate increased oxidative stress stimulates brain’s immune cells, microglia, astrocytes, secrete proinflammatory cytokines. Long-term chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, learning. Neuroprotective prevent molecules play a role addition, they improve impaired supporting neuroplasticity neurogenesis. Due important roles central nervous system diseases, elucidate review provides overview mechanisms flavonoids, which constitute large part effects, well vitamins, neurotransmitters, hormones, amino acids, derivatives. It thought understanding will enable development new therapeutic different treatment strategies.

Язык: Английский

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Multitarget Natural Compounds for Ischemic Stroke Treatment: Integration of Deep Learning Prediction and Experimental Validation

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Ischemic stroke's complex pathophysiology demands therapeutic approaches targeting multiple pathways simultaneously, yet current treatments remain limited. We developed an innovative drug discovery pipeline combining a deep learning approach with experimental validation to identify natural compounds comprehensive neuroprotective properties. Our computational framework integrated SELFormer, transformer-based model, and algorithms predict NC bioactivity against seven crucial stroke-related targets (ACE, GLA, MMP9, NPFFR2, PDE4D, eNOS). The encompassed IC50 predictions, clustering analysis, quantitative structure-activity relationship (QSAR) modeling, uniform manifold approximation projection (UMAP)-based profiling followed by molecular docking studies validation. Analysis revealed six distinct clusters unique signatures. UMAP identified 11 medium-activity (6 < pIC50 ≤ 7) 57 high-activity (pIC50 > compounds, confirming strong correlations between binding energies predicted values. In vitro using NGF-differentiated PC12 cells under oxygen-glucose deprivation demonstrated significant effects of four compounds: feruloyl glucose, l-hydroxy-l-tryptophan, mulberrin, ellagic acid. These enhanced cell viability, reduced acetylcholinesterase activity lipid peroxidation, suppressed TNF-α expression, upregulated BDNF mRNA levels. Notably, mulberrin acid showed superior efficacy in modulating oxidative stress, inflammation, neurotrophic signaling. This study establishes robust learning-driven for identifying multitarget therapeutics ischemic stroke. validated particularly acid, are promising stroke treatment development. findings demonstrate the effectiveness integrating prediction accelerating neurological disorders.

Язык: Английский

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Development of a Population Pharmacokinetic Model Characterizing the Tissue Distribution of Resveratrol After Administration by Different Routes and Doses in Rats

Nutrients, Год журнала: 2025, Номер 17(1), С. 181 - 181

Опубликована: Янв. 3, 2025

Background: Studies have demonstrated that resveratrol exerts several pharmacological effects. However, the pharmacokinetic parameters are not completely established. Objectives: This study describes plasma pharmacokinetics and tissue distribution of after administration by different routes doses in rats. Methods: A reliable, simple, sensitive HPLC method using UV detection for quantification rat tissues was developed validated. In addition, a analysis non-compartmental population modeling performed. Results: The 5 mg/kg via i.v. bolus calculated were constant elimination (ke) 0.09 h−1 ± 0.04, half-life (t1/2) 9.5 h 3.7, an apparent volume (Vd) 5.8 L/kg 4.7, clearance (Cl) 0.39 L/h/Kg 0.26, area under curve (AUC) 6076 ng/h/mL 2959. results obtained 100 p.o. 0.12 0.07 h−1, 7.9 4.2 h, 13.3 3.3 L/kg, 1.76 0.49 6519 1592 ng/h/mL. For analysis, 10 intravenously administered to rats molecule quantified liver, lung, kidney, heart, stomach, spleen, adipose tissue, brain animals. Conclusions: showed has two-compartment model both higher when it is given orally. high concentration iv administration, which indicates this capable crossing blood–brain barrier animals, crucial capacity its neuroprotective activity.

Язык: Английский

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Neuroprotective effects of hirudin against cerebral ischemia-reperfusion injury via inhibition of CCL2-mediated ferroptosis and inflammatory pathways

Brain Research Bulletin, Год журнала: 2025, Номер unknown, С. 111293 - 111293

Опубликована: Март 1, 2025

Cerebral ischemia-reperfusion injury (CIRI) is a leading cause of neurological impairment in stroke, primarily correlated to oxidative stress, inflammation, and ferroptosis. This study investigates the neuroprotective effects hirudin on CIRI, focusing its role modulating neuronal survival, ferroptosis markers through inhibition CCL2. A middle cerebral artery occlusion (MCAO) model mice an oxygen-glucose deprivation/reoxygenation (OGD/R) HT22 cells were used simulate ischemic conditions. Hirudin significantly improved function reduced edema infarct size MCAO model. In vitro, enhanced viability apoptosis OGD/R-stimulated cells. Integrative network pharmacology transcriptomic analysis identified CCL2 as potential target hirudin. treatment suppressed expression, which turn TLR4/NF-κB signaling activation, thereby mitigating inflammatory responses neurons. Overexpression partially reversed these protective effects, underscoring injury. These findings suggest that alleviates CIRI by preventing ferroptosis, offering insights into therapeutic agent for

Язык: Английский

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Post-Stroke Recovery: A Review of Hydrogel-Based Phytochemical Delivery Systems

Gels, Год журнала: 2025, Номер 11(4), С. 260 - 260

Опубликована: Апрель 1, 2025

Stroke remains a leading cause of disability worldwide, underscoring the urgent need for novel and innovative therapeutic strategies to enhance neuroprotection, support regeneration, improve functional recovery. Previous research has shown that phytochemicals such as curcumin, tannic acid, gallic ginsenosides, resveratrol, isorhamnetin display extensive neuroprotective properties, including antioxidant, anti-inflammatory, anti-apoptotic effects. These natural compounds could also promote neurogenesis, angiogenesis, preservation blood–brain barrier. Despite their promising bioactivities, clinical application is often limited by poor solubility, bioavailability, suboptimal pharmacokinetics. Hydrogels offer solution encapsulating controlling gradual release these directly at site injury. Recent advancements in hydrogel formulations, constructed from biopolymers functionalized using nanotechnological approaches, significantly stability, targeted delivery phytochemicals. Controlled profiles pH-sensitive environment-responsive hydrogels ensure compounds’ effects are optimally timed with individual critical stages post-stroke repair. Moreover, scaffolds tailored material properties biocompatibility can create favorable microenvironment, reducing secondary inflammation, enhancing tissue potentially improving cognitive outcomes following stroke. This review explores potential integrating within hydrogel-based systems specifically designed The design synthesis biocompatible, biodegradable especially applications discussed. Lastly, we emphasize additional robust translatable preclinical studies.

Язык: Английский

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Targeting the Ischemic Core: A Therapeutic Microdialytic Approach to Prevent Neuronal Death and Restore Functional Behaviors

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3821 - 3821

Опубликована: Апрель 17, 2025

Ischemic stroke leads to cerebral ionic imbalance, increases acidosis, oxidative stress and release of glutamate inflammatory mediators. Removing solute or stimulants from the ischemic core may block cell-damaging events confer neuroprotection. In this study, we developed a minimally invasive therapeutic microdialysis (tMD) method, choosing include serum albumin in buffer because it is multifunctional protein with osmotic properties. Aiming at core, continuous perfusion supplemented agents removes mediators inflammation/cell damage/death lesion. This tMD treatment significantly removed zinc ions thereby reducing infarct volumes affording high-grade neurobehavioral protection against stroke. The effectively protected neurons reduced microglial activation. Furthermore, approach extended window protect beyond 6 h after onset. These findings support potential clinical feasibility applying patients stroke, potentially without adverse effects.

Язык: Английский

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Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 28, 2025

Ischemic stroke (IS) remains a leading cause of mortality and disability worldwide, driven by genetic predispositions environmental interactions, with epigenetics playing pivotal role in mediating these processes. Specific modifying enzymes that regulate epigenetic changes have emerged as promising targets for IS treatment. DNA methyltransferases (DNMTs), ten-eleven translocation (TET) dioxygenases, histone acetyltransferases (HATs), deacetylases (HDACs) are central to regulation. These maintain dynamic balance between methylation/demethylation acetylation/deacetylation, which critically influences gene expression neuronal survival IS. This review is based on both vivo vitro experimental studies, exploring the roles DNMT/TET HAT/HDAC IS, evaluating their potential therapeutic targets, discussing use natural compounds modulators develop novel treatment strategies.

Язык: Английский

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Role of histone deacetylases and sirtuins in the ischaemic stroke: a systematic review and meta-analysis of animal studies

Stroke and Vascular Neurology, Год журнала: 2025, Номер unknown, С. svn - 004159

Опубликована: Май 7, 2025

Background Treatment of ischaemic stroke requires exploration novel neuroprotective strategies owing to the constraints thrombolytic therapy. Recent research implies that modulation histone deacetylases (HDAC) or sirtuins (SIRT) could be beneficial in achieving this goal. Methods This systematic review and meta-analysis evaluates effectiveness HDAC/SIRT enzyme treating acute stroke. It includes relevant studies but excludes human vitro non-primary studies. An electronic search was conducted across databases PubMed, Web Science Scopus until 20 March 2025. The methodological quality assessed using a modified SYRCLE risk bias tool. Infarct volume neurological responses were extracted as key outcomes, random-effects infarct for directly targeting enzymes. Results A 71 involving over 1600 animals focused on treatments, predominantly male rodents transient middle cerebral artery occlusion model. Most treatments administered intraperitoneally, starting from inception ischaemia 5 days afterwards. Non-selective HDAC inhibitors SIRT1 modulators targeted most frequently. with 95% CI showed an overall effect estimate −1.529 suggested non-selective exhibit promise reducing size. Additionally, agonists SIRT3/7, SIRT6, HDAC1, along SIRT5, HDAC6 HDAC3, may play significant role treatment Importantly, have been found effective when within 24 hours following ischaemia. Discussion study highlights promising trials by focusing outcome. However, relying exclusively not fully capture these treatments.

Язык: Английский

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