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Antioxidants as Regulators of Metabolic Pathways: Potential and Therapeutic Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 3919

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Special Issue Information

Dear Colleagues,

Metabolic pathways are the intricate networks of biochemical reactions that sustain life by converting nutrients into energy and essential biomolecules. The proper functioning of these pathways is essential for maintaining cellular homeostasis and overall health. However, metabolic processes are also a source of reactive oxygen species (ROS) which, when present in excess, can lead to oxidative stress. Oxidative stress has been implicated in the pathogenesis of many chronic diseases, including cancer, neurodegenerative disorders, cardiovascular disease, and diabetes. As a result, the regulation of oxidative stress by antioxidants has become an important area of research.

The study of antioxidants as modulators of metabolic pathways is not only fundamental to understanding disease mechanisms but also has significant therapeutic potential. Targeting oxidative stress with antioxidant therapies offers a promising approach to managing and potentially preventing metabolic disorders and their complications. In addition, advances in our understanding of how specific antioxidants interact with metabolic pathways may lead to the development of more effective and targeted treatments.

This Special Issue, entitled “Antioxidants as Regulators of Metabolic Pathways: Potential and Therapeutic Strategies” aims to highlight the latest scientific developments in this rapidly evolving field. It will cover a wide range of research topics, from the molecular mechanisms underlying antioxidant action in metabolic regulation to preclinical and clinical studies exploring their therapeutic applications. By bringing together cutting-edge research, this Special Issue aims to provide a comprehensive overview of the current state and future directions in the use of antioxidants to modulate metabolic pathways, ultimately contributing to the development of novel therapeutic strategies for a wide range of diseases.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  1. Mechanisms of antioxidant action in metabolic pathways.
  2. Role of antioxidants in regulating glucose metabolism.
  3. Impact of antioxidants on lipid metabolism and cardiovascular health.
  4. Antioxidants in energy metabolism.
  5. Antioxidants and insulin sensitivity.
  6. Therapeutic potential of antioxidants in metabolic disorders.
  7. Dietary antioxidants and their impact on metabolic pathways.
  8. Redox regulation of metabolic enzymes.
  9. Antioxidants and mitochondrial function.
  10. Synergistic effects of antioxidants and metabolic pathway modulators.
  11. Molecular mechanisms of antioxidant-induced metabolic reprogramming.
  12. Comparative studies of antioxidants and metabolic pathways across species.

Dr. Halina Tkaczenko
Prof. Dr. Natalia Kurhaluk
Guest Editors

Manuscript Submission Information

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Keywords

  • antioxidants
  • metabolic pathways
  • oxidative stress
  • cellular homeostasis
  • redox signaling
  • energy metabolism
  • lipid metabolism
  • therapeutic strategies
  • chronic diseases

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Published Papers (2 papers)

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Research

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35 pages, 16365 KiB  
Article
The Role of Hydrogen Sulfide in iNOS and APP Localization and Expression in Neurons and Glial Cells Under Traumatic Effects: An Experimental Study with Bioinformatics Analysis and Biomodeling
by Stanislav Rodkin, Chizaram Nwosu and Evgeniya Kirichenko
Int. J. Mol. Sci. 2024, 25(22), 11892; https://doi.org/10.3390/ijms252211892 - 5 Nov 2024
Cited by 1 | Viewed by 1122
Abstract
Hydrogen sulfide (H2S) donors are emerging as promising candidates for neuroprotective agents. However, H2S-dependent neuroprotective mechanisms are not yet fully understood. We have demonstrated that an H2S donor (sodium sulfide, Na2S) reduces the expression of [...] Read more.
Hydrogen sulfide (H2S) donors are emerging as promising candidates for neuroprotective agents. However, H2S-dependent neuroprotective mechanisms are not yet fully understood. We have demonstrated that an H2S donor (sodium sulfide, Na2S) reduces the expression of inducible NO synthase (iNOS) and amyloid-beta precursor protein (APP) in damaged neural tissue at 24 h and 7 days following traumatic brain injury (TBI). The application of aminooxyacetic acid (AOAA), an inhibitor of cystathionine β-synthase (CBS), produced the opposite effect. Seven days after TBI, iNOS expression was observed not only in the cytoplasm but also in some neuronal nuclei, while APP was exclusively localized in the cytoplasm and axons of damaged neurons. It was also shown that iNOS and APP were present in the cytoplasm of mechanoreceptor neurons (MRNs) in the crayfish, in axons, as well as in certain glial cells 8 h after axotomy. Na2S and AOAA had opposing effects on axotomized MRNs and ganglia in the ventral nerve cord (VNC). Multiple sequence alignments revealed a high degree of identity among iNOS and APP amino acid residues in various vertebrate and invertebrate species. In the final stage of this study, biomodeling identified unique binding sites for H2S, hydrosulfide anion (HS), and thiosulfate (S2O32−) with iNOS and APP. Full article
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Review

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42 pages, 3983 KiB  
Review
Antioxidant-Rich Functional Foods and Exercise: Unlocking Metabolic Health Through Nrf2 and Related Pathways
by Halina Tkaczenko and Natalia Kurhaluk
Int. J. Mol. Sci. 2025, 26(3), 1098; https://doi.org/10.3390/ijms26031098 - 27 Jan 2025
Cited by 2 | Viewed by 2444
Abstract
This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on the underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web of Science, PsycINFO, and reference lists of relevant reviews up to 20 December [...] Read more.
This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on the underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web of Science, PsycINFO, and reference lists of relevant reviews up to 20 December 2024, highlighting the central role of the Nrf2 pathway. As a critical regulator of oxidative stress and metabolic adaptation, Nrf2 mediates the benefits of these interventions. This article presents an innovative approach to understanding the role of Nrf2 in the regulation of oxidative stress and inflammation, highlighting its potential in the prevention and treatment of various diseases, including cancer, neurodegenerative disorders, cardiovascular and pulmonary diseases, diabetes, inflammatory conditions, ageing, and infections such as COVID-19. The novelty of this study is to investigate the synergistic effects of bioactive compounds found in functional foods (such as polyphenols, flavonoids, and vitamins) and exercise-induced oxidative stress on the activation of the Nrf2 pathway. This combined approach reveals their potential to improve insulin sensitivity and lipid metabolism and reduce inflammation, offering a promising strategy for the management of chronic diseases. However, there are significant gaps in current research, particularly regarding the molecular mechanisms underlying the interaction between diet, physical activity, and Nrf2 activation, as well as their long-term effects in different populations, including those with chronic diseases. In addition, the interactions between Nrf2 and other critical signalling pathways, including AMPK, NF-κB, and PI3K/Akt, and their collective contributions to metabolic health are explored. Furthermore, novel biomarkers are presented to assess the impact of these synergistic strategies, such as the NAD+/NADH ratio, the GSH ratio, and markers of mitochondrial health. The findings provide valuable insights into how the integration of an antioxidant-rich diet and regular exercise can improve metabolic health by activating Nrf2 and related molecular pathways and represent promising strategies for the prevention and treatment of metabolic disorders. Further studies are needed to fully understand the therapeutic potential of these interventions in diseases related to oxidative stress, such as cardiovascular disease, neurodegenerative disease, diabetes, and cancer. Full article
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