The Role of Oxidative Stress in Trisomy 21 Phenotype

Buczyńska, Angelika; Sidorkiewicz, Iwona; Krętowski, Adam Jacek; Zbucka-Krętowska, Monika

doi:10.1007/s10571-023-01417-6

Cited by 3 publications

(1 citation statement)

References 198 publications

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“…6 The future of antioxidant treatment discussion: considerations and opportunities for metformin intervention Since oxidative stress is involved in the pathogenesis of many diseases, it is crucial to find ways to overcome its negative impact (Blacker and Duchen, 2016;Buczyńska et al, 2021a;Adamska et al, 2021;Buczyńska et al, 2021b;Buczyńska et al, 2023a;Buczyńska et al, 2023b;Buczyńska et al, 2023c;Kościuszko et al, 2023). This review focused on presenting new and promising mechanisms responsible for the potential antioxidant use of metformin, while forecasting further research directions (Salvatore et al, 2021).…”

Section: Metformin As An Antioxidant In Clinical Trials: Advancement ...mentioning

confidence: 99%

Examining the clinical relevance of metformin as an antioxidant intervention

Buczyńska,

Sidorkiewicz,

Krętowski

et al. 2024

Front. Pharmacol.

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In physiological concentrations, reactive oxygen species play a vital role in regulating cell signaling and gene expression. Nevertheless, oxidative stress is implicated in the pathogenesis of numerous diseases and can inflict damage on diverse cell types and tissues. Thus, understanding the factors that mitigate the deleterious effects of oxidative stress is imperative for identifying new therapeutic targets. In light of the absence of direct treatment recommendations for reducing oxidative stress, there is a continuing need for fundamental research that utilizes innovative therapeutic approaches. Metformin, known for its multifaceted beneficial properties, is acknowledged for its ability to counteract the adverse effects of increased oxidative stress at both molecular and cellular levels. In this review, we delve into recent insights regarding metformin’s antioxidant attributes, aiming to expand its clinical applicability. Our review proposes that metformin holds promise as a potential adjunctive therapy for various diseases, given its modulation of oxidative stress characteristics and regulation of diverse metabolic pathways. These pathways include lipid metabolism, hormone synthesis, and immunological responses, all of which may experience dysregulation in disease states, contributing to increased oxidative stress. Furthermore, our review introduces potential novel metformin-based interventions that may merit consideration in future research. Nevertheless, the necessity for clinical trials involving this drug remains imperative, as they are essential for establishing therapeutic dosages and addressing challenges associated with dose-dependent effects.

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Section: Metformin As An Antioxidant In Clinical Trials: Advancement ...mentioning

confidence: 99%

Examining the clinical relevance of metformin as an antioxidant intervention

Buczyńska,

Sidorkiewicz,

Krętowski

et al. 2024

Front. Pharmacol.

Self Cite

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Genomic instability and oxidative stress markers in pregnant women presenting fetal malformation

Maraslis,

Jacobsen-Pereira,

Parisotto

et al. 2024

Gene Reports

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Network Pharmacology Identifies Intersection Genes of Apigenin and Naringenin in Down Syndrome as Potential Therapeutic Targets

Amir,

Shafi,

Parveen

et al. 2024

Pharmaceuticals

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Down Syndrome (DS), characterized by trisomy of chromosome 21, leads to the overexpression of several genes contributing to various pathologies, including cognitive deficits and early-onset Alzheimer’s disease. This study aimed to identify the intersection genes of two polyphenolic compounds, apigenin and naringenin, and their potential therapeutic targets in DS using network pharmacology. Key proteins implicated in DS, comprising DYRK1A, APP, CBS, and ETS2, were selected for molecular docking and dynamics simulations to assess the binding affinities and stability of the protein–ligand interactions. Molecular docking revealed that naringenin exhibited the highest binding affinity to DYRK1A with a score of −9.3 kcal/mol, followed by CBS, APP, and ETS2. Moreover, molecular docking studies included positive control drugs, such as lamellarin D, valiltramiprosate, benserazide, and TK216, which exhibited binding affinities ranging from −5.5 to −8.9 kcal/mol. Apigenin showed strong binding to APP with a score of −8.8 kcal/mol, suggesting its potential in modulating amyloid-beta levels. These interactions were further validated through molecular dynamics simulations, demonstrating stable binding throughout the 100 ns simulation period. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses indicated minimal fluctuations, confirming the stability of the complexes. The findings suggest that apigenin and naringenin could serve as effective therapeutic agents for DS by targeting key proteins involved in its pathology. Future studies should focus on in vivo validation, clinical trials, and exploring combination therapies to fully harness the therapeutic potential of these compounds for managing DS. This study underscores the promising role of network pharmacology in identifying novel therapeutic targets and agents for complex disorders like DS.

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The Role of Oxidative Stress in Trisomy 21 Phenotype

Cited by 3 publications

References 198 publications

Examining the clinical relevance of metformin as an antioxidant intervention

Examining the clinical relevance of metformin as an antioxidant intervention

Genomic instability and oxidative stress markers in pregnant women presenting fetal malformation

Network Pharmacology Identifies Intersection Genes of Apigenin and Naringenin in Down Syndrome as Potential Therapeutic Targets

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