Investigating the Neuroprotective and Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 393 - 393

Published: March 25, 2024

The aging of the global population has increased prevalence neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic quercetin, demonstrates potential for brain health. Limited research been conducted on therapeutic applications BM in This systematic review aims to project BM’s beneficial role disorders. anti-apoptotic antioxidant actions can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, increase neuroprotection. included twenty-two clinical trials demonstrated that reduce Nuclear Factor-κB phosphorylation, emotional cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, psychiatric problems. Moreover, levels pro-inflammatory biomarkers oxidative stress. Here, we highlight provides notable benefits serve a complementary approach care patients conditions associated adds growing interest natural products their by improving our understanding mechanisms underlying function neurodegeneration informing development new strategies diseases.

Language: Английский

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Apigenin-mediated MARK4 inhibition: a novel approach in advancing Alzheimer’s disease therapeutics

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Language: Английский

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Exploring the potential of baicalin and resveratrol as PIM-1 kinase inhibitors: Therapeutic targeting of prostate and breast cancers

Journal of Molecular Liquids, Journal Year: 2024, Volume and Issue: 396, P. 124026 - 124026

Published: Jan. 22, 2024

Language: Английский

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The neuroprotective potential of phytochemicals in traumatic brain injury: mechanistic insights and pharmacological implications

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Traumatic brain injury (TBI) leads to damage, comprising both immediate primary damage and a subsequent cascade of secondary mechanisms. The results in localized while the initiates inflammatory responses, followed by disruption blood-brain barrier, infiltration peripheral blood cells, edema, release various immune mediators, including chemotactic factors interleukins. TBI disrupts molecular signaling, cell structures, functions. In addition physical tissue such as axonal injuries, contusions, haemorrhages, interferes with functioning, impacting cognition, decision-making, memory, attention, speech capabilities. Despite deep understanding pathophysiology TBI, an intensive effort evaluate underlying mechanisms effective therapeutic interventions is imperative manage repercussions TBI. Studies have commenced explore potential employing natural compounds for These are characterized their low toxicity limited interactions conventional drugs. Moreover, many demonstrate capacity target aspects process. While our there urgent need mitigate its consequences. Here, we aimed summarize mechanism action role phytochemicals against progression. This review discusses implications phytonutrients addresses consequences addition, highlighted roles emerging promising candidates intervention highlights neuroprotective mechanistic approach. Furthermore, efforts focused on mechanisms, providing better therapeutics.

Language: Английский

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Therapeutic targeting of microtubule affinity‐regulating kinase 4 in cancer and neurodegenerative diseases

Journal of Cellular Biochemistry, Journal Year: 2023, Volume and Issue: 124(9), P. 1223 - 1240

Published: Sept. 1, 2023

Abstract Microtubule affinity‐regulating kinase 4 (MARK4) is a member of the Ser/Thr protein family, phosphorylates microtubule‐connected proteins and plays vital role in causing cancers neurodegenerative diseases. This modulates multiple signaling pathways, including mammalian target rapamycin, nuclear factor‐κB, Hippo‐signaling, presumably responsible for cancer Alzheimer's. MARK4 acts as negative controller Hippo‐kinase cassette promoting YAP/TAZ action, loss detains tumorigenic properties cells. involved tau hyperphosphorylation that consequently affects neurodegeneration. promising drug cancer, diabetes, Developing potent selective inhibitors MAKR4 are therapeutic management associated Despite its great significance, few reviews available to discuss structure, function clinical significance. In current review, we aimed provide detailed information on structural features targeted development various pathways related We further described potential preventing numerous Finally, updated will be helpful effective molecules.

Language: Английский

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Promising Natural Remedies for Alzheimer’s Disease Therapy

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 922 - 922

Published: Feb. 17, 2025

This study examines the intricacies of Alzheimer's disease (AD), its origins, and potential advantages various herbal extracts natural compounds for enhancing memory cognitive performance. Future studies into AD treatments are encouraged by review's demonstration effectiveness phytoconstituents that were extracted from a number plants. In addition to having many beneficial effects, such as improved cholinergic function, medicines also much less harmful, more readily available, easier use than other treatments. They pass without difficulty through blood-brain barrier (BBB). focused on substances their effects using academic databases identify peer-reviewed published between 2015 2024. According literature review, 66 isolated 21 distinct plants have shown efficacy, which could be encouraging future research therapies. Since most clinical trials produce contradictory results, suggests larger-scale with longer treatment durations necessary validate or refute therapeutic efficacy

Language: Английский

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Identification of potential inhibitors of Fyn-Kinase from bioactive phytochemicals of Berberis lycium for therapeutic targeting of neurodegenerative disease

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 18

Published: Feb. 24, 2025

Fyn is classified as a member of the Src family kinases (SFKs), group non-receptor tyrosine kinases. It critical component many fundamental central nervous system (CNS) processes. Recently, connection has been shown between malfunction and pathogenic processes exhibited in neurodegenerative conditions, such Alzheimer's disease (AD), which significant factor worldwide mortality disability. Due to rising demographic elderly individuals, there projected increase incidence AD forthcoming years. This study aims identify prospective phytochemicals that can be utilized developing new protein kinase inhibitor for therapeutic intervention AD. The lack interventions capable preventing progression concern thus, it imperative potential targets. employed virtual screening approach discover Fyn-kinase inhibitors from Berberis lycium (B.ly.) phytoconstituents. Three molecules, Canadine, N-Methyltetrahydroberberine (N-MTHB), Tetrahydroberberine (THB), were found have strong affinity binding pocket kinase. docked complexes B.ly. compounds with underwent all-atom molecular dynamics (MD) simulations assess their stability interactions. MD simulation analysis revealed identified show promise inhibitors, may implicated management

Language: Английский

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Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer’s disease therapeutics

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 19, 2025

Neurodegeneration is a progressive loss of neurons that leads to affected cognitive and motor functions characterized by neurodegenerative disorders (NDs). Human transferrin (Htf) blood plasma glycoprotein binds iron regulates the free in biological fluids. Free potent neurotoxin associated with generation Reactive oxygen species (ROS) ultimately linked oxidative stress neuronal damage. Thus, targeting homeostasis an attractive strategy for management NDs, viz. Alzheimer's disease (AD). Tryptamine (Trp) naturally occurring monoamine, has demonstrated promising roles AD therapeutics. The present study aims delineate binding mechanism Trp Htf employing computational spectroscopic approaches. Molecular docking ascertained vital residues governing Htf-Trp complex formation. Further, dynamic (MD) studies structural dynamics stability complex, implying causes minimal alterations Htf, suggestive complex. results from fluorescence spectroscopy constant ( K ) 0.48 × 10 6 M −1 , validating silico observations. This provides platform understand may lead novel therapeutic approaches AD.

Language: Английский

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Experimental and theoretical studies on structural changes in the microtubule affinity-regulating kinase 4 (MARK4) protein induced by N-hetarenes: a new class of therapeutic candidates for Alzheimer’s disease

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: March 19, 2025

Introduction Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively affects the cognitive function and memory of affected person. Unfortunately, only handful effective prevention or treatment options are available today. Microtubule affinity-regulating kinase 4 (MARK4) serine/threonine protein plays critical role in regulating microtubule dynamics facilitating cell division. The dysregulated expression MARK4 has been associated with range diseases, including AD. Methods In this study, we synthesized series N -hetarenes via Pd(0)-catalyzed Suzuki-Miyaura cross coupling reaction. All compounds were characterized using multi-spectroscopic techniques evaluated for their activity against enzyme through ATPase inhibition assays. experimental data was further supported by computational quantum chemical calculations. We also computed drug-likeness, bioavailability, toxicity (ADME/T) profiles compounds. Results Six new 4-(6-(arylpyrimidin-4-yl)piperazine-1-carboximidamides 5−10 prepared good yields. assay conducted on these demonstrated IC 50 values micromolar (5.35 ± 0.22 to 16.53 1.71 μM). Among tested compounds, 4-(6-( p -tolyl)pyrimidin-4-yl)piperazine-1-carboximidamide ( 5 ; = 5.35 μM) 4-(6-(benzo[ b ]thiophen-2-yl)pyrimidin-4-yl)piperazine-1-carboximidamide 9 6.68 0.80 showed best activity. binding constant K ), as determined fluorescence quenching estimated be 1.5 0.51 × 10 M −1 1.14 0.26 . results molecular docking MD simulation studies (PDB: 5ES1) indicated able bind ATP pocket MARK4, leading its stabilization. Additionally, ADME/T analysis revealed high degree drug-likeness Conclusion 4-(6-(arylpyrimidin-4-yl)piperazine-1-carboximidamides) promising class developing next-generation anti-AD drugs. reported inhibited in-vitro at concentration targeting ATP-binding pocket. These findings provide valuable insights future drug design.

Language: Английский

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Mechanistic insights into the inhibition of microtubule affinity-regulating kinase 4 by Syringic acid: A computational and experimental study

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142812 - 142812

Published: April 1, 2025

Language: Английский

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