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

Deadline for manuscript submissions: 20 May 2026 | Viewed by 6728

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Prof. Dr. Demetrios Kouretas

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Guest Editor

Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, Greece
Interests: antioxidant; oleuropein; elenolic acid
Special Issues, Collections and Topics in MDPI journals

Dr. Fotios Tekos

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Guest Editor

Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, Greece
Interests: antioxidants; redox; polyphenol; fasting; oxidative stress; glutathione; natural products; stress; toxicology
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Special Issue Information

Dear Colleagues,

Oxidative stress plays a crucial role in the pathogenesis of various diseases, including neurodegenerative disorders, cardiovascular diseases, and cancer. Antioxidants, whether derived from natural sources or synthetically developed, are essential for counteracting oxidative damage and maintaining cellular homeostasis.

In this Special Issue, we aim to explore cutting-edge research on the mechanisms of antioxidant activity, novel antioxidant compounds, and their applications in human health. We welcome original research and review articles which address molecular pathways, bioavailability, therapeutic potential, and advancements in the analytical techniques used to assess antioxidant efficacy.

Prof. Dr. Demetrios Kouretas
Dr. Fotios Tekos
Guest Editors

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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.

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Keywords

xenobiotics
oxidative stress
free radicals
reactive oxygen species
reactive nitrogen species
antioxidants
glutathione
toxicology
redox metabolism
redox imbalance

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Published Papers (7 papers)

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Research

Jump to: Review

11 pages, 652 KB

Open AccessArticle

Spectroscopy-Based Evaluation of the Antioxidant Capacity of Hemp (Cannabis sativa)

by Mariola Bartoszek, Justyna Polak, Paweł Gała, Michał Zieliński, Krzysztof Nawrot and Mirosław Chorążewski

Int. J. Mol. Sci. 2025, 26(23), 11696; https://doi.org/10.3390/ijms262311696 - 3 Dec 2025

Viewed by 179

Abstract

In the present study, a comprehensive evaluation of the antioxidant properties of various parts of the hemp plant, specifically its leaves and flowers, in a new feminized variety of Cannabis sativa with an admixture of Cannabis ruderalis was investigated. Methods such as Electron Paramagnetic Resonance (EPR) and UV-visible (UV-vis) spectroscopy were used to assess trolox equivalent antioxidant capacity (TEAC) and total polyphenol content (TPC). TEAC values of the analyzed samples ranged from 29.5 μmol TE/g DW to 150.2 μmol TE/g DW, while TPC varied between 5.4 mg GAE/g DW and 20.3 mg GAE/g DW. The findings indicate that hemp exhibits significant antioxidant properties, especially in its leaves. This is attributed to a diverse range of antioxidants, including cannabinoids, flavonoids, and phenolic compounds, which offer notable health benefits. Furthermore, the method of drying hemp has been shown to influence its antioxidant properties significantly. Research indicates that freeze-dried and air-dried hemp retains higher levels of antioxidant compounds compared to other drying methods. This suggests that selecting an appropriate drying technique is essential for preserving the bioactive compounds responsible for hemp’s antioxidant activity. Full article

(This article belongs to the Special Issue Advanced Research in Antioxidant Activity)

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14 pages, 2278 KB

Open AccessArticle

The Phytochemical Potential of Viola Species, Melanium Subgenus, Subsection Bracteolatae

by Elida Rosenhech, Andrei Lobiuc, Irina Boz and Maria-Magdalena Zamfirache

Int. J. Mol. Sci. 2025, 26(23), 11614; https://doi.org/10.3390/ijms262311614 - 30 Nov 2025

Viewed by 243

Abstract

This study provides a comparative phytochemical evaluation of five Viola L. species belonging to the Melanium subgenus, subsection Bracteolatae: V. declinata, V. dacica, V. tricolor, V. arvensis, and V. kitaibeliana. Plant material was collected from natural populations in northeastern Romania, encompassing both alpine and agricultural habitats. We analyzed assimilatory pigments, anthocyanins, total phenolics, flavonoids, and antioxidant activity from aqueous and 50% ethanolic extracts (four plant-to-solvent ratios). Results showed that V. dacica and V. declinata, two Carpathian endemic taxa, had the highest contents of anthocyanins and phenolic compounds, which strongly correlated with their antioxidant activity. The quantitative analyses of total phenols for V. dacica were up to 94.81 ± 1.37 mg gallic acid equivalents/gram (GAE/g) (1% hydroalcoholic extract), and for anthocyanins were up to 113 ± 0.128 mg/g. Meanwhile, for V. declinate, total phenols were up to 95.53 ± 0.33 mg GAE/g (1% hydroalcoholic extract), and for anthocyanins, were up 0.909 ± 0.054 mg/g. V. kitaibeliana extracts, although obtained from lowland populations, were distinguished by elevated flavonoid concentrations, up to 56.61 ± 1.19 mg quercetin equivalents/gram (QE/g) dry biomass (0.5% hydroalcoholic extract). In contrast, V. arvensis and V. tricolor, cosmopolitan and widely used in traditional medicine, exhibited lower levels of bioactive compounds under the same extraction conditions. These findings highlight the pharmaceutical and ecological potential of less-studied Viola species and provide the first quantitative comparative data for V. dacica, V. declinata, and V. kitaibeliana. The results support the valorization of these taxa as valuable sources of bioactive secondary metabolites with antioxidant properties. Full article

(This article belongs to the Special Issue Advanced Research in Antioxidant Activity)

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19 pages, 2179 KB

Open AccessArticle

Unveiling the Skin Anti-Aging Potential of the Novel Spirulina platensis Extract Elixspir^®

by Chiara Donati, Giulia Nerina Nardone, Vera Mason, Emanuela Di Gregorio, Irene Ragusa, Emanuele Amadio, Eleonora Zampieri, Rebecca Bassetto, Valentina Gandin and Samuele Zanatta

Int. J. Mol. Sci. 2025, 26(23), 11372; https://doi.org/10.3390/ijms262311372 - 25 Nov 2025

Viewed by 393

Abstract

Arthrospira platensis (commonly known as Spirulina platensis) is a blue-green microalga increasingly used in skincare due to its antioxidant and dermo-protective properties, primarily attributed to components such as phycocyanin and carotenoids. However, the intense blue color of phycocyanin can limit its cosmetic appeal. In this study, we investigated the antioxidant, anti-inflammatory, skin lightening and photoprotective activity of Elixspir^®, a novel light-colored aqueous extract of Spirulina, using both 2D and 3D skin cell models. We demonstrated that Elixspir^® exerts strong antioxidant and cytoprotective effects by reducing intracellular ROS levels and modulating cellular thiol redox state. Its anti-pigmentation potential was supported by tyrosinase inhibition, while anti-inflammatory activity was principally due to ability to reduce PGE2 levels. Finally, we demonstrated an unprecedented photoprotective effect of Elixspir^®, highlighting its potential as a novel active ingredient for skin defense against environmental stressors. Overall, these results provide a molecular-level understanding of Elixspir^® multifunctional bioactivity and support its application as a skin-lightening, anti-inflammatory, antioxidant, and photoprotective ingredient in the formulation of innovative skin anti-aging treatments. Full article

(This article belongs to the Special Issue Advanced Research in Antioxidant Activity)

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28 pages, 5358 KB

Open AccessArticle

Exploring the Effects of Palm Tocotrienol-Rich Fraction in Diabetic Peripheral Neuropathy Rat’s Model: An Untargeted Metabolomic Profiling and Correlation Study

by Noradliyanti Rusli, Jen Kit Tan, Suzana Makpol, Isma Liza Mohd Isa, Nur Haleeda Hakimi, Nazirah Ab Rani and Rabani Remli

Int. J. Mol. Sci. 2025, 26(23), 11247; https://doi.org/10.3390/ijms262311247 - 21 Nov 2025

Viewed by 277

Abstract

Persistent and chronic hyperglycaemia in Type II diabetic mellitus (DM) is known to cause oxidative stress, which exacerbates underlying metabolic disorders, contributing to the progression of complications such as diabetic peripheral neuropathy (DPN). Palm tocotrienol-rich fraction (TRF) is renowned for its potent antioxidative and neuroprotective properties and might have the potential to halt or mitigate the severity of DPN. This study aimed to investigate the effects of palm TRF on diabetic rats with peripheral neuropathy and to identify the correlation between plasma metabolomic alterations and DPN parameters. Male Sprague Dawley (SD) rats were randomly divided into normal control and DM groups in which Type II DM was induced using a high-fat diet and a low-dose streptozotocin (STZ) (35 mg/kg). Successful diabetic rats were randomly divided and received daily oral treatments of palm olein (vehicle), metformin (70 mg/kg), TRF (60 mg/kg), or a combination of TRF and metformin for 12 weeks. Behavioural parameters, serum biomarkers, and plasma metabolomic profiling were assessed at 0 (baseline) and 12 weeks of intervention. From the behavioural parameters, improvement in the symptoms of thermal hyperalgesia and mechanical allodynia was seen with TRF interventions, either alone or in combination with metformin. A significant reduction in the neurofilament light (NEFL) chain, accompanied by a notable increase in nerve growth factor (NGF) levels in the serum of treatment groups, was also observed. From the plasma samples, findings reveal that TRF increases metabolites related to neurotransmitter pathways (acetylcholine, choline, phenylalanine, tryptophan) and decreases inflammatory metabolites (kynurenine, prostaglandin) compared to untreated diabetic rats. These metabolites, except for prostaglandin, showed positive correlations with pain sensitivity. In contrast, prostaglandin showed opposite correlations with pain and nerve damage markers, suggesting its potential role in inflammation and axonal injury. Full article

(This article belongs to the Special Issue Advanced Research in Antioxidant Activity)

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20 pages, 5023 KB

Open AccessArticle

Protective Effects of Methanolic Extract of Micromeria frivaldszkyana (Degen) Velen Against Acetaminophen-Induced Liver Toxicity in Male Wistar Rats

by Elisaveta Apostolova, Kristina Stavrakeva, Vesela Kokova, Ivica Dimov, Mariya Choneva, Delyan Delev, Ilia Kostadinov, Ilia Bivolarski, Maria Koleva, Rumen Mladenov, Plamen Stoyanov and Anelia Bivolarska

Int. J. Mol. Sci. 2025, 26(18), 9112; https://doi.org/10.3390/ijms26189112 - 18 Sep 2025

Viewed by 703

Abstract

Acetaminophen (APAP) overdose can result in potentially fatal acute liver failure, with free radical formation identified as a major mechanism of liver tissue damage. Micromeria frivaldszkyana (M. frivaldszkyana), a rare species endemic to Bulgaria, has demonstrated significant antioxidant activity. Male Wistar rats were treated orally for 7 days with saline; 250, 400, or 500 mg/kg of a water solution of dried methanolic extract of M. frivaldszkyana; 100 mg/kg rosmarinic acid (RA); or 125 mg/kg silymarin. Liver toxicity was induced by oral application of 2000 mg/kg APAP on the last day of treatment. Forty-eight hours later, blood and livers were collected for histological and biochemical analysis. The results revealed that treatment with 500 mg/kg of the dried methanolic extract significantly reduced the elevated levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and tumor necrosis factor-alpha in APAP overdose. The present results clearly demonstrate, for the first time, that pre-treatment with methanolic extract of M. frivaldszkyana results in significant hepatoprotective effects in the APAP-induced rat model of liver injury. The mechanism of this effect may involve cell membrane protection, decreased lipid peroxidation and DNA damage, and attenuation of aseptic inflammation. These effects can be attributed to the main compounds identified in the extract (linarin, chlorogenic acid, rutin, eupatorin, apigenin, RA). Full article

(This article belongs to the Special Issue Advanced Research in Antioxidant Activity)

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20 pages, 3567 KB

Open AccessArticle

In Vivo Neuroprotective Effects of Alpinetin Against Experimental Ischemic Stroke Damage Through Antioxidant and Anti-Inflammatory Mechanisms

by Ratchaniporn Kongsui, Sitthisak Thongrong and Jinatta Jittiwat

Int. J. Mol. Sci. 2025, 26(11), 5093; https://doi.org/10.3390/ijms26115093 - 26 May 2025

Cited by 5 | Viewed by 2185

Abstract

Ischemic stroke is the most common type of stroke and poses a major global health challenge due to its high mortality and lasting disability impact. The onset and progression of ischemic stroke are largely linked to oxidative stress and inflammatory responses. Alpinetin, a natural flavonoid found in the ginger family, exhibits various pharmacological properties, including antioxidant and anti-inflammatory activities. In this study, the neuroprotective potential of alpinetin in attenuating oxidative stress and inflammation against cerebral ischemic stroke was evaluated. Ninety male Wistar rats were randomly assigned to the sham operation group, the Rt.MCAO group, the Rt.MCAO+piracetam group, and the Rt.MCAO+alpinetin groups (25, 50, and 100 mg/kg BW). Cerebral infarction size, neuronal density, and antioxidant and anti-inflammatory activities were measured. Three days of treatment with alpinetin markedly reduced the infarct volume by 30% compared to the Rt.MCAO+vehicle-treated group. Additionally, rats treated with alpinetin exhibited a significant increase in neuronal density in the cortex, as well as in the CA1 and CA3 regions of the hippocampus. Furthermore, treatment with alpinetin ameliorated both the Rt.MCAO-induced increase in malondialdehyde (MDA) activity and the Rt.MCAO-induced decrease in catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in the cortex and hippocampus. Moreover, COX-2 and IL-6 protein levels were assessed using western blotting. The results showed that treatment with alpinetin (100 mg/kg BW) significantly reduced the expression levels of COX-2 and IL-6 in both the cortex and hippocampus. Our findings suggest that alpinetin significantly mitigates the effects of cerebral ischemia-induced brain damage through its antioxidant and anti-inflammatory properties and could potentially be developed as a therapeutic agent for stroke treatment. Full article

(This article belongs to the Special Issue Advanced Research in Antioxidant Activity)

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Review

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23 pages, 633 KB

Open AccessReview

Exogenous Pyruvate in Defense Against Human-Exposure Toxicants: A Review of In Vitro and In Vivo Evidence

by Iwona Zwolak

Int. J. Mol. Sci. 2025, 26(17), 8316; https://doi.org/10.3390/ijms26178316 - 27 Aug 2025

Viewed by 2019

Abstract

Pyruvate is an alpha-keto acid that occurs naturally in living cells. It is a key metabolite in cellular respiration and a substrate for the synthesis of glucose (in gluconeogenesis) and certain amino acids. Exogenous pyruvate, for example in the form of sodium pyruvate or ethyl pyruvate, has potential therapeutic applications due to its antioxidant and anti-inflammatory properties. This review summarises cell culture and animal studies that report the cytoprotective effects of exogenous pyruvate compounds during exposure to environmental pollutants, drugs, UV radiation, and burns. These reports show that the main mechanisms through which exogenous pyruvate exerts its beneficial effects are the neutralisation of reactive oxygen species, protection and stabilisation of mitochondria, maintenance of ATP levels, and inhibition of inflammatory signalling pathways, including the nuclear factor-kappa B (NF-κB) pathway. The article also outlines potential challenges associated with the therapeutic use of exogenous pyruvate. These include the instability of inorganic pyruvate (sodium pyruvate) and the fact that the metabolism of ethyl pyruvate differs between humans and animals. Full article

(This article belongs to the Special Issue Advanced Research in Antioxidant Activity)

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