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Phytochemicals and Antioxidants in Health and Disease Modulation
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Phytochemicals and Antioxidants in Health and Disease Modulation

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

Deadline for manuscript submissions: 30 July 2026 | Viewed by 2629

Special Issue Editor

Prof. Dr. Natalia Kurhaluk

E-Mail Website
Guest Editor
Institute of Biology, Pomeranian Uniwersity in Słupsk, Słupsk, Poland
Interests: pollution-induced oxidative damage; toxicity and oxidative injury; heavy metals; ecotoxicology; ecophysiology; nitric oxide; environmental stressors; environmental stressors in human and animal health; antioxidant defense in pathology; redox imbalance in human and animal diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Phytochemicals are bioactive compounds that are naturally present in fruits, vegetables and herbs. They are increasingly recognised for their role in promoting health and preventing disease by affecting inflammation, oxidative stress and cellular signalling. Compounds such as flavonoids, polyphenols, carotenoids and glucosinolates are key dietary components and potential modulators of chronic disease processes, attracting significant research interest.

Antioxidants, whether dietary or endogenous, are essential for neutralising reactive oxygen species and maintaining cellular homeostasis, particularly in conditions such as cancer, cardiovascular disease, diabetes and neurodegeneration, where oxidative stress contributes to disease progression. This Special Issue emphasises molecular-level studies that explore the mechanisms, bioavailability, metabolism and synergistic effects of phytochemicals and antioxidants. Importantly, the exact active ingredient of the natural origin extract must be reported in the submitted research manuscript, as papers describing the effects of mixed extractions from natural origins do not fall within the scope of this journal.

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

- Molecular mechanisms of phytochemicals in health and disease modulation, including signalling pathways
- Antioxidant activity and oxidative stress-related molecular pathways
- Bioavailability, metabolism and pharmacokinetics of plant-derived compounds
- Anti-inflammatory and immunomodulatory effects of bioactive compounds via molecular signalling cascades.
- Flavonoids, polyphenols, carotenoids and other phytochemicals with defined molecular targets.
- Cellular and molecular pathways influenced by dietary compounds.
- Nutritional interventions and their molecular impact on chronic diseases.
- Synergistic effects of phytochemicals and antioxidants at the molecular and cellular level.
- Translational and clinical studies linking molecular findings to human health.

As a journal focusing on molecular research, IJMS can only process manuscripts that include molecular data. We invite original research, reviews and perspectives that advance the understanding of how these compounds modulate health and disease, thereby informing nutritional strategies and therapeutic approaches.

Prof. Dr. Natalia Kurhaluk
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • phytochemical bioactive compounds
  • antioxidant mechanisms
  • oxidative stress modulation
  • chronic disease prevention
  • inflammatory signalling pathways
  • molecular health effects
  • bioavailability and metabolism
  • flavonoid biological activity
  • polyphenol therapeutic potential
  • disease modulation strategies

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Published Papers (3 papers)

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Research

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12 pages, 1217 KB  
Article
Osthole Activates FGF21 Expression by Mediating Activation of ATF4 in Human Hepatocyte HepG2 Cells
by Akishi Taguchi, Masaya Araki, Tomoya Yamashita, Ryo Kanazawa, Itsuki Terao, Kyohei Suzuki, Yuhei Tsuchimoto, Takashi Matsuzaka, Hirohito Sone, Hitoshi Shimano and Yoshimi Nakagawa
Int. J. Mol. Sci. 2026, 27(2), 1003; https://doi.org/10.3390/ijms27021003 - 19 Jan 2026
Viewed by 620
Abstract
Osthole is a natural coumarin derivative found in several medicinal plants, including Cnidium monnieri and Angelica pubescens. It has been studied for its various biological properties, such as anti-inflammatory, neuroprotective, osteogenic, cardioprotective, antimicrobial, and antiparasitic effects. Osthole was found to induce Fibroblast [...] Read more.
Osthole is a natural coumarin derivative found in several medicinal plants, including Cnidium monnieri and Angelica pubescens. It has been studied for its various biological properties, such as anti-inflammatory, neuroprotective, osteogenic, cardioprotective, antimicrobial, and antiparasitic effects. Osthole was found to induce Fibroblast growth factor 21 (FGF21) expression. Among the known transcription factors that regulate FGF21 induction, activating transcription factor 4 (ATF4) expression was found to be upregulated by osthole. Additionally, as osthole induced ATF4 downstream gene expression, it was concluded that it activates ATF4 signaling. ATF4 knockdown significantly suppressed osthole-mediated induction of FGF21 expression. These findings suggest that osthole activates FGF21 expression via ATF4 activation. Full article
(This article belongs to the Special Issue Phytochemicals and Antioxidants in Health and Disease Modulation)
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Review

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41 pages, 4279 KB  
Review
Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations
by Natalia Kurhaluk, Renata Kołodziejska, Lyudmyla Buyun, Piotr Kamiński and Halina Tkaczenko
Int. J. Mol. Sci. 2026, 27(8), 3461; https://doi.org/10.3390/ijms27083461 - 12 Apr 2026
Viewed by 956
Abstract
Nitrate-rich vegetables are increasingly recognised as a key subgroup of phytochemical-dense foods that have significant potential for preventing and managing chronic diseases. Although dietary nitrates were historically approached with caution due to concerns about nitrosamine formation, contemporary evidence highlights their beneficial effects on [...] Read more.
Nitrate-rich vegetables are increasingly recognised as a key subgroup of phytochemical-dense foods that have significant potential for preventing and managing chronic diseases. Although dietary nitrates were historically approached with caution due to concerns about nitrosamine formation, contemporary evidence highlights their beneficial effects on vascular, metabolic and cognitive functions. Ageing is characterised by endothelial dysfunction, impaired nitric oxide (NO) synthesis and increased oxidative stress, which elevates cardiovascular risk. In this context, nitrate-rich vegetables offer a natural way to restore NO bioavailability and support cardiometabolic health. This narrative review provides an integrative overview of nitrate-rich vegetables as sources of bioactive phytochemicals with therapeutic relevance. We summarise the biochemical pathways of nitrate and nitrite metabolism, including the enterosalivary nitrate–nitrite–NO cycle, the role of oral microbiota, and red blood cell-mediated nitrite reduction. Particular emphasis is placed on NOS-independent NO production, which becomes increasingly important with age, and on the synergistic interactions between dietary nitrates and other phytochemicals such as polyphenols, vitamin C, flavonoids and betalains. These compounds enhance NO stability, reduce oxidative stress, modulate inflammatory signalling and support mitochondrial function, thereby amplifying the health benefits of nitrate-rich vegetables. Beetroot, with its high nitrate content and distinctive antioxidant profile, is highlighted as a prime example. Clinical and mechanistic studies suggest that nitrate-rich vegetables may lower blood pressure, improve endothelial function and cerebral perfusion, enhance cognitive performance and muscle oxygenation, and increase exercise efficiency, particularly in older adults. Additional benefits include anti-inflammatory effects, modulation of platelet function and improvements in metabolic parameters, all of which are relevant to the prevention of chronic diseases such as hypertension, type 2 diabetes and atherosclerosis. While dietary nitrate is generally considered low-risk for healthy adults, caution is warranted in susceptible populations, such as infants and individuals with impaired renal function. Finally, significant research gaps remain, including the need for long-term, well-controlled trials and personalised strategies that account for variability in microbiota composition and nitrate metabolism between individuals. Full article
(This article belongs to the Special Issue Phytochemicals and Antioxidants in Health and Disease Modulation)
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29 pages, 2373 KB  
Review
Curcumin Between Pleiotropic Potential and Translational Constraints
by Alessandro Magini and Alessandro Datti
Int. J. Mol. Sci. 2026, 27(5), 2212; https://doi.org/10.3390/ijms27052212 - 26 Feb 2026
Cited by 2 | Viewed by 780
Abstract
Curcumin is widely recognized for its anti-inflammatory and antioxidant properties; however, this conventional framing obscures a broader, complex, and mechanistically diverse pharmacology. Here, we advance a refined perspective that situates curcumin within a hierarchical and multilayered architecture shaped by the dynamic interplay of [...] Read more.
Curcumin is widely recognized for its anti-inflammatory and antioxidant properties; however, this conventional framing obscures a broader, complex, and mechanistically diverse pharmacology. Here, we advance a refined perspective that situates curcumin within a hierarchical and multilayered architecture shaped by the dynamic interplay of intrinsic chemical reactivity, metabolic transformation and exposure, and microbial modulation. From this standpoint, curcumin functions as a network-level modulator, producing context-dependent outcomes rather than uniform or linear responses. Consequently, its biological influence extends well beyond traditional paradigms, engaging pathways involved in xenobiotic metabolism, membrane transport, immune and metabolic signaling, and host-microbiome interactions, with downstream implications for drug disposition and biomarker interpretation. This complexity is further compounded by rapid clearance and limited systemic availability, although partially offset by the functional relevance of bioactive metabolites. Consistent with this pleiotropic model, clinical signals of curcumin activity tend to emerge in conditions characterized by multifactorial dysregulation, including metabolic, neurocognitive, and musculoskeletal disorders, as well as microbiome-associated alterations. Notably, human studies and meta-analyses frequently report divergent outcomes, with some trials demonstrating benefit and others showing substantial between-study heterogeneity. To reconcile these discrepancies, we advocate a High Input, Rational Integration paradigm that unifies experimental, preclinical, and clinical evidence obtained through logically rigorous and strictly consistent procedures applied across comprehensive, convergent, and reproducible datasets. Within the hierarchical organization of curcumin’s pharmacology, this approach enables the synthesis of mechanistic diversity within pharmacokinetic and physiological constraints and, more broadly, provides a coherent framework for interpreting pleiotropic bioactives in human studies. Full article
(This article belongs to the Special Issue Phytochemicals and Antioxidants in Health and Disease Modulation)
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