Antioxidants

18 pages, 4820 KiB

Open AccessArticle

Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway

by Zhibin Liu, Ke Huang, Hai Huang, Eungyung Kim, Hyeonjin Kim, Chae Yeon Kim, Dong Joon Kim, Sang In Lee, Sangsik Kim, Do Yoon Kim, Kangdong Liu, Zae Young Ryoo, Mee-Hyun Lee, Lei Ma and Myoung Ok Kim

Antioxidants 2025, 14(6), 694; https://doi.org/10.3390/antiox14060694 (registering DOI) - 8 Jun 2025

Abstract

Esophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a [...] Read more.

Esophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a natural compound with potent antioxidant properties in cancer and cardiovascular diseases. However, its specific effects and mechanisms in ESCC remain largely unexplored. This study aims to investigate the effects of IQ in ESCC cells and elucidate the mechanisms underlying its therapeutic effects. Specifically, its impact on cell proliferation, colony formation, migration, and invasion was assessed using cell viability assay, morphology, transwell, and colony formation assays. The effects on apoptosis were evaluated by flow cytometry, while immunofluorescence (IF) staining and Western blotting were performed to confirm the underlying mechanisms. The in vivo anti-cancer effects of IQ were then evaluated using a xenograft tumor model. Our results demonstrate that IQ inhibits ESCC cell growth and colony formation while promoting its apoptosis by enhancing caspase activation and downregulating Bcl-2 expression. Furthermore, IQ suppresses cell migration by modulating the epithelial–mesenchymal transition-related proteins. Additionally, IQ induces excessive autophagy by promoting reactive oxygen species accumulation and inhibiting the AKT/mTOR signaling pathway. Importantly, IQ effectively reduces tumor growth in vivo, highlighting its potential as a therapeutic agent for ESCC. Full article

(This article belongs to the Special Issue Redox Signaling in Cancer: Mechanisms and Therapeutic Opportunities)

28 pages, 6586 KiB

Open AccessArticle

The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H₂S in Drosophila melanogaster

by Victoria Y. Shilova, David G. Garbuz, Lyubov N. Chuvakova, Alexander P. Rezvykh, Sergei Y. Funikov, Artem I. Davletshin, Svetlana Y. Sorokina, Ekaterina A. Nikitina, Olga Gorenskaya, Michael B. Evgen’ev and Olga G. Zatsepina

Antioxidants 2025, 14(6), 693; https://doi.org/10.3390/antiox14060693 - 6 Jun 2025

Abstract

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H₂S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of [...] Read more.

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H₂S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of H₂S production in flies showed minimal levels in the double- and triple-knockout strains. The double- (cbs-/-; cse-/-) and triple- (cbs-/-; cse-/-; dtst-/-) KO flies exhibited a shortened lifespan and reduced fecundity, and showed dramatic changes in Malpighian tubule morphology. The transcriptomic analysis revealed a profound increase in the expression levels of several genes involved in excretory system function in the double-KO and especially the triple-KO flies. Importantly, major groups of differentially expressed genes (DEGs) in the whole bodies of females and ovaries of KO strains included genes responsible for detoxification, reproduction, mitochondrial activity, excretion, cell migration, and muscle system function. The reduced fecundity observed in the double- and triple-KO flies correlated with pronounced changes in the ovarian transcriptome. At the same time, the single knockout of dtst1 increased the flies’ fecundity and lifespan. Our experiments exploring unique Drosophila strains with KO of major H₂S-related genes revealed several new pathways controlled by this ancient adaptogenic system that is involved in various human diseases and aging. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

23 pages, 6273 KiB

Open AccessArticle

Dynamic Transcriptomic and Cellular Remodeling Underlie Cuprizone-Induced Demyelination and Endogenous Repair in the CNS

by Yantuanjin Ma, Tianyi Liu, Zhipeng Li, Wei Wei, Qiting Zhao and Shufen Wang

Antioxidants 2025, 14(6), 692; https://doi.org/10.3390/antiox14060692 - 6 Jun 2025

Abstract

Demyelination in the central nervous system (CNS) disrupts neuronal communication and promotes neurodegeneration. Despite the widespread use of cuprizone-induced demyelination models to study myelin injury and repair, the mechanisms underlying oligodendrocyte apoptosis and regeneration are poorly understood. This study investigated the dynamic cellular [...] Read more.

Demyelination in the central nervous system (CNS) disrupts neuronal communication and promotes neurodegeneration. Despite the widespread use of cuprizone-induced demyelination models to study myelin injury and repair, the mechanisms underlying oligodendrocyte apoptosis and regeneration are poorly understood. This study investigated the dynamic cellular and molecular changes that occur during demyelination and remyelination, with a focus on glial cell responses, blood-brain barrier (BBB) integrity, and neuroimmune interactions. C57BL/6J mice exposed to cuprizone exhibited weight loss, sensorimotor deficits, and cognitive decline, which were reversed during remyelination. Histological and immunofluorescence analyses revealed reduced myelin protein levels, including myelin basic protein (MBP) and myelin-associated glycoprotein (MAG), and decreased oligodendrocyte populations during demyelination, with recovery during repair. The BBB permeability increases during demyelination, is associated with the decreased expression of tight junction proteins (ZO-1, Occludin), and normalizes during remyelination. Single-cell RNA sequencing revealed dynamic shifts in glial cell populations and upregulated Psap-Gpr37l1 signaling. Neuroimmune activation and oxidative stress peak during demyelination, characterized by elevated ROS, MDA, and immune cell infiltration, followed by recovery. Transcriptomic profiling revealed key inflammatory pathways (JAK-STAT, NF-κB) and hub genes associated with demyelination and repair. These findings provide insights into myelin repair mechanisms and highlight potential therapeutic targets for treating demyelinating diseases. Full article

► Show Figures

Figure 1

30 pages, 1408 KiB

Open AccessReview

Dynamic Interplay Between Autophagy and Oxidative Stress in Stem Cells: Implications for Regenerative Medicine

by Daniela Rossin, Maria-Giulia Perrelli, Marco Lo Iacono, Raffaella Rastaldo and Claudia Giachino

Antioxidants 2025, 14(6), 691; https://doi.org/10.3390/antiox14060691 - 6 Jun 2025

Abstract

The crosstalk between autophagy and oxidative stress is a cornerstone of stem cell biology. These processes are tightly interwoven, forming a regulatory network that impacts stem cell survival, self-renewal, and differentiation. Autophagy, a cellular recycling mechanism, ensures the removal of damaged organelles and [...] Read more.

The crosstalk between autophagy and oxidative stress is a cornerstone of stem cell biology. These processes are tightly interwoven, forming a regulatory network that impacts stem cell survival, self-renewal, and differentiation. Autophagy, a cellular recycling mechanism, ensures the removal of damaged organelles and proteins, thereby maintaining cellular integrity and metabolic balance. Oxidative stress, driven by the accumulation of reactive oxygen species (ROS), can act as both a signalling molecule and a source of cellular damage, depending on its levels and context. The interplay between autophagy and oxidative stress shapes stem cell fate by either promoting survival under stress conditions or triggering senescence and apoptosis when dysregulated. Recent evidence underscores the bidirectional relationship between these processes, where autophagy mitigates oxidative damage by degrading ROS-generating organelles, and oxidative stress can induce autophagy as a protective response. This crosstalk is critical not only for preserving stem cell function but also for addressing age-related decline and enhancing regenerative potential. Understanding the molecular mechanisms that govern this interplay offers novel insights into stem cell biology and therapeutic strategies. This review delves into the intricate molecular dynamics of autophagy and oxidative stress in stem cells, emphasizing their synergistic roles in health, disease, and regenerative medicine applications. Full article

(This article belongs to the Special Issue Crosstalk between Autophagy and Oxidative Stress)

► Show Figures

Figure 1

2 pages, 590 KiB

Open AccessCorrection

Correction: Kuo et al. Involvement of HO-1 and Autophagy in the Protective Effect of Magnolol in Hepatic Steatosis-Induced NLRP3 Inflammasome Activation In Vivo and In Vitro. Antioxidants 2020, 9, 924

by Ni-Chun Kuo, Shieh-Yang Huang, Chien-Yi Yang, Hsin-Hsueh Shen and Yen-Mei Lee

Antioxidants 2025, 14(6), 690; https://doi.org/10.3390/antiox14060690 - 5 Jun 2025

Abstract

In the original publication [...] Full article

► Show Figures

Figure 1

23 pages, 6844 KiB

Open AccessArticle

A Hydrolyzed Soybean Protein Enhances Oxidative Stress Resistance in C. elegans and Modulates Gut–Immune Axis in BALB/c Mice

by Jun Liu, Yansheng Zhao, Fei Leng, Xiang Xiao, Weibo Jiang and Shuntang Guo

Antioxidants 2025, 14(6), 689; https://doi.org/10.3390/antiox14060689 - 5 Jun 2025

Abstract

Soy protein isolate (SPI) is a high-purity protein from defatted soybeans, providing emulsifying and gelling functions for plant-based foods and supplements. Hydrolysis can facilitate the production of bioactive small-molecule proteins or peptides with potential functional applications. In this study, 20% hydrolyzed soy protein [...] Read more.

Soy protein isolate (SPI) is a high-purity protein from defatted soybeans, providing emulsifying and gelling functions for plant-based foods and supplements. Hydrolysis can facilitate the production of bioactive small-molecule proteins or peptides with potential functional applications. In this study, 20% hydrolyzed soy protein (20% HSP) was prepared from SPI, and the effects of 20% HSP and SPI on alleviating oxidative stress in Caenorhabditis elegans (C. elegans) and regulating immune–gut microbiota in cyclophosphamide (CTX)-induced immunocompromised BALB/c mice were investigated. In C. elegans, both SPI and 20% HSP (300 μg/mL) enhanced locomotive activities, including body bending and head thrashing, and improved oxidative stress resistance under high glucose conditions. This improvement was mediated by increased antioxidant enzyme activities (SOD, CAT, and GSH-Px), while malondialdehyde (MDA) content was reduced by 60.15% and 82.28%, respectively. Both of them can also significantly extend the lifespan of normal C. elegans and paraquat-induced oxidative stress models by inhibiting lipofuscin accumulation. This effect was mediated through upregulation of daf-16 and suppression of daf-2 and akt-1 expression. In immunocompromised mice, 20% HSP alleviated CTX-induced immune dysfunction by increasing peripheral white blood cells and lymphocytes, attenuating thymic atrophy, and reducing hepatic oxidative stress via MDA inhibition. Gut microbiota analysis revealed that 20% HSP restored microbial balance by suppressing Escherichia-Shigella and enriching beneficial genera, like Psychrobacter. These findings highlight 20% HSP and SPI’s conserved anti-aging mechanisms via daf-16 activation in C. elegans and immune–gut modulation in mice, positioning them as plant-derived nutraceuticals targeting oxidative stress and immune dysregulation. Full article

(This article belongs to the Special Issue The Interaction Between Gut Microbiota and Host Oxidative Stress)

► Show Figures

Figure 1

23 pages, 3875 KiB

Open AccessArticle

Chemical Composition, Quality, and Bioactivity of Laurus nobilis L. Hydrosols from the Adriatic Regions of Croatia: Implications for Dermatological Applications

by Lea Juretić, Valerija Dunkić, Ivana Gobin, Suzana Inić, Dario Kremer, Marija Nazlić, Lea Pollak, Silvestar Mežnarić, Ana Barbarić and Renata Jurišić Grubešić

Antioxidants 2025, 14(6), 688; https://doi.org/10.3390/antiox14060688 - 5 Jun 2025

Abstract

Laurus nobilis L., Lauraceae, bay laurel, has been traditionally used for its various therapeutic properties, and in recent years has been gaining interest for its potential applications in skincare products. However, the biological effects of bay laurel, particularly its hydrosols, a water fraction [...] Read more.

Laurus nobilis L., Lauraceae, bay laurel, has been traditionally used for its various therapeutic properties, and in recent years has been gaining interest for its potential applications in skincare products. However, the biological effects of bay laurel, particularly its hydrosols, a water fraction obtained during essential oil production, remain unexplored. The objective of this study was to identify the volatile compounds in L. nobilis hydrosols (LnHYs) from different coastal regions of Croatia (north, middle, and south Adriatic) and to evaluate their potential safety and efficacy for dermatological applications. Upon isolating LnHYs using microwave-assisted extraction, LnHY volatiles were identified and quantified using gas chromatography and mass spectrometry. Oxygenated monoterpenes were the dominant compounds in all LnHYs (61.72–97.00%), with 1,8-cineole being the most abundant component (52.25–81.89%). The physical and chemical parameters of LnHYs were investigated to assess their purity and quality. Biological activity (cytotoxicity and wound-healing effect) was tested on the human keratinocyte cell line (HaCaT), selected as the experimental model due to its relevance to skin biology. Additionally, contents of polyphenolic substances, antioxidative effects using the Oxygen Radical Absorbance Capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods, and the antimicrobial activity of LnHYs toward five skin microorganisms were determined. All tested hydrosols showed similar biological activity, with only minor differences. Cytotoxicity studies indicated the safety of the dermatological application of LnHYs, and the results of the wound-healing assay showed their neutral to mildly positive effect. Considering the growing use of bay laurel preparations in pharmaceutical and cosmetic applications, extensive studies on their biological activity, quality, and safety are essential to either support or regulate their use in humans. Full article

► Show Figures

Figure 1

2 pages, 445 KiB

Open AccessCorrection

Correction: Longhitano et al. The Crosstalk between GPR81/IGFBP6 Promotes Breast Cancer Progression by Modulating Lactate Metabolism and Oxidative Stress. Antioxidants 2022, 11, 275

by Lucia Longhitano, Stefano Forte, Laura Orlando, Stephanie Grasso, Alessandro Barbato, Nunzio Vicario, Rosalba Parenti, Paolo Fontana, Angela M. Amorini, Giuseppe Lazzarino, Giovanni Li Volti, Michelino Di Rosa, Arcangelo Liso, Barbara Tavazzi, Giacomo Lazzarino and Daniele Tibullo

Antioxidants 2025, 14(6), 687; https://doi.org/10.3390/antiox14060687 - 5 Jun 2025

Abstract

In the original publication, there was a mistake in Figure 4C as published [...] Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

► Show Figures

Figure 4

19 pages, 5284 KiB

Open AccessArticle

Phosphorus Supplementation Enhances Growth and Antioxidant Defense Against Cadmium Stress in Cotton

by Asif Iqbal, Huiping Gui, Cangsong Zheng, Xiangru Wang, Xiling Zhang, Meizhen Song and Xiaoyan Ma

Antioxidants 2025, 14(6), 686; https://doi.org/10.3390/antiox14060686 - 5 Jun 2025

Abstract

Cadmium (Cd) contamination in agricultural soils is increasing due to anthropogenic activities, posing a significant threat to plant growth and productivity. Phosphorus (P) has been suggested as a potential mitigator of Cd toxicity, yet the role of cotton genotypes with contrasting low-P tolerance [...] Read more.

Cadmium (Cd) contamination in agricultural soils is increasing due to anthropogenic activities, posing a significant threat to plant growth and productivity. Phosphorus (P) has been suggested as a potential mitigator of Cd toxicity, yet the role of cotton genotypes with contrasting low-P tolerance in contaminated soils remains largely unexplored. A hydroponic experiment was conducted to assess the effects of Cd stress (5 μM) on Jimian169 (strong-low-P tolerant) and DES926 (weak-low-P tolerant) cotton genotypes under low-P (0.01 mM KH₂PO₄) and normal P (1 mM KH₂PO₄) conditions. The results revealed that Cd stress, especially under low-P, significantly reduced plant growth, dry matter, photosynthetic rate, and P use efficiency (PUE), while increasing oxidative damage through increased malonaldehyde levels and reactive oxygen species accumulation. These adverse impacts were very much evident in DES926 compared to Jimian169. In contrast, Jimian169 demonstrated greater resilience to Cd stress by mitigating oxidative damage through enhanced antioxidant enzyme activity, improved photosynthetic performance, and increased accumulation of osmoprotectants. These findings indicate that Jimian169 can better withstand Cd toxicity by enhancing photosynthesis, antioxidant defense mechanisms, and osmotic adjustment. This makes them a promising candidate for cultivation in Cd-contaminated, P-deficient soils. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants, 2nd Edition)

► Show Figures

Figure 1

21 pages, 1000 KiB

Open AccessArticle

Selenium and Coenzyme Q₁₀ Supplementation and Sex Differences in Cardiovascular Mortality Results from a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly People Low in Selenium

by Urban Alehagen, Jan Olav Aaseth, Lutz Schomburg, Trine B. Opstad, Anders Larsson and Jan Alexander

Antioxidants 2025, 14(6), 685; https://doi.org/10.3390/antiox14060685 - 5 Jun 2025

Abstract

Background: Low selenium intake and age-related decline of coenzyme Q₁₀ (CoQ₁₀) have been associated with an increased risk of cardiovascular disease (CVD) and oxidative stress. In a randomised placebo-controlled trial (RTC) in elderly people with low selenium levels, the supplementation [...] Read more.

Background: Low selenium intake and age-related decline of coenzyme Q₁₀ (CoQ₁₀) have been associated with an increased risk of cardiovascular disease (CVD) and oxidative stress. In a randomised placebo-controlled trial (RTC) in elderly people with low selenium levels, the supplementation with selenium and CoQ₁₀ reduced CVD and mortality. However, whether the supplementation elicited sex-specific benefits remained to be explored. Methods: Elderly Swedish persons (n = 443; balanced sex ratio) receiving selenium yeast (200 µg/day) and CoQ₁₀ (200 mg/day) combined or a placebo for four years were followed for additional six years. The response to supplementation, cardiovascular (CV) mortality, and risk factors were determined at four and ten years. Kaplan–Meier analyses, ANCOVA, repeated measurements of variance, and Cox proportional hazard regression analyses were performed. Results: The measured 10-year CV mortality rate was lower in females, and supplementation reduced this risk to a greater extent compared to in males. The improved survival rate apparently kicked in later in females than in males. At baseline, males had a higher smoking rate, increased inflammation and oxidative stress, and a higher prevalence of more advanced ischaemic heart disease (IHD) and signs of heart failure. When stratified by sex, in individuals with IHD, the intervention improved CV survival in both sexes, whereas supplementation had a more pronounced effect in females without IHD at inclusion. Supplementation diminished inflammation and oxidative stress, impaired the increase of NT-proBNP, and improved renal function in both sexes. Conclusions: The supplementation improved CV survival, especially in women. The higher prevalence of structural CVD and smoking in males may have contributed to the observed greater supplementation benefits in females. The preventive impact of selenium and CoQ₁₀ supplementation in elderly males and females may be particularly strong and meaningful in the early stages of CVD development. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

► Show Figures

Figure 1

14 pages, 1129 KiB

Open AccessArticle

Culture Medium Enriched with Ultrafine Carbon Monoxide Bubbles Enhances In Vitro Blastocyst Formation of In Vivo-Fertilized Mouse Zygotes

by Toyofumi Hirakawa, Kazuhiko Nakabayashi, Noriko Ito, Keisuke Ishiwata, Daichi Urushiyama, Kohei Miyata, Tsukasa Baba, Kenichiro Hata, Shin’ichiro Yasunaga, Fusanori Yotsumoto, Katsuro Tachibana and Shingo Miyamoto

Antioxidants 2025, 14(6), 684; https://doi.org/10.3390/antiox14060684 - 4 Jun 2025

Abstract

Oxidative stress induced by in vitro culture conditions impedes the differentiation of fertilized zygotes. Gasotransmitters containing carbon monoxide (CO) exhibit antioxidant properties when exogenously administered at appropriate concentrations. In this study, CO was incorporated into ultrafine bubbles (UFBs) to devise an innovative method [...] Read more.

Oxidative stress induced by in vitro culture conditions impedes the differentiation of fertilized zygotes. Gasotransmitters containing carbon monoxide (CO) exhibit antioxidant properties when exogenously administered at appropriate concentrations. In this study, CO was incorporated into ultrafine bubbles (UFBs) to devise an innovative method for promoting the efficient differentiation of fertilized mouse zygotes into blastocysts within an in vitro culture environment. While CO typically dissipates rapidly in culture media, its encapsulation into UFBs enabled its prolonged retention within the medium. Fertilized mouse zygotes cultured in the UFB medium exhibited a significantly higher rate of blastocyst hatching compared to those cultured in conventional media. Furthermore, Gene Ontology analysis revealed elevated expression of mitochondrial-related genes and genes essential for blastocyst maturation in the UFB culture medium. These findings underscore the potential of CO-UFB as a potent agent for improving in vitro blastocyst formation and hatching by mitigating oxidative stress, thereby offering a promising strategy for enhancing assisted reproductive technologies. Full article

► Show Figures

Figure 1

27 pages, 2941 KiB

Open AccessArticle

Multivariate Evaluation of Biofunctional Metabolites in Korean Soybean Cultivars by Use Categories: Assessment of Antioxidant and Enzyme Inhibition Activities

by Kye Man Cho, Se Hyeon Jeon, Eun Jeong Ko, Dong Hyun Park, Ye Ri Jeong, Du Yong Cho, Jeong Ho Kim and Jin Hwan Lee

Antioxidants 2025, 14(6), 683; https://doi.org/10.3390/antiox14060683 - 4 Jun 2025

Abstract

This research investigates the metabolite composition and biofunctional activiteies of 41 Korean soybeans, categorized by application: bean sprout, bean paste, vegetable, and cooked-with-rice. Isoflavones were identified via UPLC-Q-TOF-MS/MS and quantified using HPLC, revealing malonylgenistin as the predominant composition (average 743.4 μg/g, 42.3% of [...] Read more.

This research investigates the metabolite composition and biofunctional activiteies of 41 Korean soybeans, categorized by application: bean sprout, bean paste, vegetable, and cooked-with-rice. Isoflavones were identified via UPLC-Q-TOF-MS/MS and quantified using HPLC, revealing malonylgenistin as the predominant composition (average 743.4 μg/g, 42.3% of total isoflavones). Bean sprout showed the highest average isoflavone (2780.6 μg/g), followed by bean paste (1837.8 μg/g), cooked-with-rice (1448.2 μg/g), and vegetable (883.2 μg/g), with significant differences in individual cultivars. Protein ranged from 36.8 to 46.6% and oil from 17.0 to 22.3%, with vegetable soybeans exhibiting the highest average protein (44.9%) and lowest average oil (18.6%). Moreover, PLS-DA and hierarchical clustering revealed distinct metabolic patterns in usage groups. Antioxidant activities (radical scavenging; DNA protection) and enzyme inhibition (tyrosinase; α-glucosidase) also varied significantly, correlating with isoflavone distributions. Particularly, Sorog exhibited the highest isoflavone (3722.7 μg/g) and strong antioxidant activity (DPPH: 72.2%; ABTS: 93.8%, 500 μg/mL), DNA protection (92.8%, 200 μg/mL), and inhibition of tyrosinase and α-glucosidase by 78.4% and 84.2% (500 μg/mL). These findings suggest that isoflavone-rich bean sprout soybeans, especially Sorog, are promising candidates for health-promoting foods and functional cultivar development. This is the first systematic study comparing the metabolites and health-related properties of soybeans based on Korean usage categories. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Natural Products—2nd Edition)

► Show Figures

Graphical abstract

15 pages, 996 KiB

Open AccessReview

The Impact of the Skin Microbiome and Oxidative Stress on the Initiation and Development of Cutaneous Chronic Wounds

by Manuela Martins-Green, Jane Kim and Klara Aziz

Antioxidants 2025, 14(6), 682; https://doi.org/10.3390/antiox14060682 - 4 Jun 2025

Abstract

Wound healing is a very complex process composed of several phases in which precise events occur, both temporally and specially. However, when these processes go awry, biofilm-forming bacteria become installed in the healing tissue, and the patient has comorbidities, so the wounds do [...] Read more.

Wound healing is a very complex process composed of several phases in which precise events occur, both temporally and specially. However, when these processes go awry, biofilm-forming bacteria become installed in the healing tissue, and the patient has comorbidities, so the wounds do not heal and become chronic. In this review, we describe the importance of high levels of oxidative stress (OS) and bacteria from the skin microbiome in the initiation and development of chronic wounds. The skin microbiome is diverse in humans, and its composition is dependent on the environment in the specific areas of the body. OS is critical for wound healing as it stimulates the immune system to destroy pathogens and secrete cytokines and growth factors that stimulate healing. When OS levels become high in the wound and the bacteria of the skin install themselves in the wound, chronicity ensues. However, neither OS nor the bacteria of the skin alone can initiate chronicity. However, when present together, chronic wounds develop. Given the complexity of chronic wound initiation, developing treatment for these wounds has been difficult. Here, we also discuss the challenges of treating chronic wounds and offer a potential sequence of approaches to treating these wounds after debridement. Full article

(This article belongs to the Special Issue Antioxidant Delivery Strategies for Prevention and Treatment of Skin Pathologies)

► Show Figures

Figure 1

29 pages, 9043 KiB

Open AccessArticle

Arginine-Mediated Liver Immune Regulation and Antioxidant Defense in Largemouth Bass (Micropterus salmoides): Multi-Omics Insights into Metabolic Remodeling During Nocardia seriolae Infection

by Yu-Long Sun, Shuai-Liang Zhang, Feng-Feng Zhou, Yuan-Xin Qian, Yang He, Run-Zhe Zhang, Fen Dong, Qiang Chen, Han-Ying Xu, Ji-Teng Wang, Yu-Ting Deng and Tao Han

Antioxidants 2025, 14(6), 681; https://doi.org/10.3390/antiox14060681 - 3 Jun 2025

Abstract

The liver of fish is an essential metabolic organ that also serves an immune regulatory role. In this study, we constructed a model of largemouth bass (Micropterus salmoides) infected with Nocardia seriolae by injection to explore the immune and antioxidant functions [...] Read more.

The liver of fish is an essential metabolic organ that also serves an immune regulatory role. In this study, we constructed a model of largemouth bass (Micropterus salmoides) infected with Nocardia seriolae by injection to explore the immune and antioxidant functions of the liver. The results showed that N. seriolae infection caused severe pathological changes in the liver, including cell necrosis, granuloma formation, and leukocyte infiltration. The level of mRNA expression of immune-related genes in the liver was significantly increased 2 days post-infection. Moreover, the combined analysis of transcriptome and metabolome showed that N. seriolae infection markedly affected liver metabolism, including glutathione metabolism, arginine and proline metabolism, arachidonic acid metabolism, as well as starch and sucrose metabolism. Additionally, multiple key biomarkers were identified as involved in regulating responses to N. seriolae infection, including arginine, glutathione, gpx, GST, PLA2G, GAA, and PYG. To further elucidate the regulatory effects of arginine on the immune and antioxidant processes in the liver, primary hepatocytes were isolated and cultured. The results demonstrated that arginine supplementation significantly reduced the expression of LPS-induced apoptosis-related genes (bax, cas3, cas8, and cas9) by up to 50% while increasing the expression of antioxidant genes (gpx, GST) by up to 700% at 24 h. Through the analysis of metabolic changes and immune responses in the liver following N. seriolae infection, combined with in-vitro experiments, this study elucidated the anti-apoptotic and antioxidant effects of arginine, revealing the immune response mechanisms in fish liver and laying the groundwork for using nutritional strategies to improve fish health. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)

► Show Figures

Figure 1

19 pages, 2137 KiB

Open AccessArticle

Optimization of Ultrasound-Assisted Extraction of Phenolic Compounds from Romanian Blackthorn (Prunus spinosa L.) Fruits

by Ana-Maria Drăghici-Popa, Oana Cristina Pârvulescu, Raluca Stan and Ana-Maria Brezoiu

Antioxidants 2025, 14(6), 680; https://doi.org/10.3390/antiox14060680 - 3 Jun 2025

Abstract

Selecting factors that significantly affect the extraction process and optimizing them are essential to obtain high extraction efficiency. This study aimed at optimizing the ultrasonic-assisted extraction (UAE) of polyphenols from Romanian blackthorn fruits using aqueous solutions of ethanol as green extraction solvents. Six [...] Read more.

Selecting factors that significantly affect the extraction process and optimizing them are essential to obtain high extraction efficiency. This study aimed at optimizing the ultrasonic-assisted extraction (UAE) of polyphenols from Romanian blackthorn fruits using aqueous solutions of ethanol as green extraction solvents. Six process factors, including solvent/plant material ratio (R_LS = 4.95–15.1 cm³/g), ethanol concentration in the extraction solvent (c_et = 16.4–83.6%), extraction temperature (t = 30–70 °C), pH of the solvent (pH = 2–7), amplitude of the ultrasonic probe (A = 30–70%), and extraction time (τ = 5–15 min), were screened and optimized based on a Plackett–Burman design (PBD) and a central composite design (CCD). Statistical analysis indicated that R_LS, c_et, and t significantly affected the process response variables in terms of total phenolic content (TPC), total anthocyanins content (TAC), and antioxidant capacity (AC). Under optimal conditions (R_LS_,opt = 15.1 cm³/g, c_et_,opt = 33.2%, t_opt = 66.8 °C, pH_opt = 7, A_opt = 50%, and τ_opt = 10 min), the following levels of response variables were experimentally determined: TPC_opt = 14.45 ± 0.718 mg GAE/g DM, TAC_opt = 0.405 ± 0.057 mg C3GE/g DM, and AC_opt = 16.75 ± 1.144 mg TE/g DM. Six phenolic compounds were identified in the extract obtained at optimal levels of process factors, i.e., rutin (7.12 ± 0.06 mg/100 g DM), protocatechuic acid (6.83 ± 0.01 mg/100 g DM), neochlorogenic acid (4.88 ± 0.01 mg/100 g DM), vanillic acid (3.70 ± 0.01 mg/100 g DM), chlorogenic acid (1.93 ± 0.02 mg/100 g DM), and caffeic acid (1.51 ± 0.01 mg/100 g DM). Full article

(This article belongs to the Special Issue Green Extraction of Antioxidant from Natural Source)

► Show Figures

Figure 1

18 pages, 2421 KiB

Open AccessArticle

ELONGATED HYPOCOTYL5 Regulates Resistance to Root-Knot Nematode by Modulating Antioxidant System and Jasmonic Acid in Cucumis sativus

by Fusheng Ma, Juanqi Li, Mengwei Huang, Mengyan E, Dandan Cui, Guoxiu Wu, Shengli Li and Yang Li

Antioxidants 2025, 14(6), 679; https://doi.org/10.3390/antiox14060679 - 3 Jun 2025

Abstract

Root-knot nematodes (RKNs), specifically Meloidogyne incognita, are notoriously difficult to eliminate as endophytic nematodes, and cause severe damage to various plants. Cucumber (Cucumis sativus), which is a cash crop widely grown across the world, is often infected by RKNs. ELONGATED [...] Read more.

Root-knot nematodes (RKNs), specifically Meloidogyne incognita, are notoriously difficult to eliminate as endophytic nematodes, and cause severe damage to various plants. Cucumber (Cucumis sativus), which is a cash crop widely grown across the world, is often infected by RKNs. ELONGATED HYPOCOTYL5 (HY5), a member of the bZIP transcription factor family, plays a vital role in hormone, nutrient, abiotic stress, biotic stress, and oxygen species (ROS) signaling pathways. However, the involvement of HY5 in the defense against RKNs has rarely been reported. The present study initially explored the response of CsHY5 to RKNs. The results indicated that the hy5 mutant had a higher number of nematodes and galls in the root system and exhibited a higher susceptibility to RKNs compared with the wild type (WT). Particularly, the root-knot nematodes in hy5 plants completed their life cycle more quickly and produced more eggs. The activities of defense-related hormones and antioxidant enzymes were measured, and the results indicated that JA, jasmonoyl-isoleucine (JA-Ile), abscisic acid (ABA), peroxidase (POD), and ascorbate peroxidase (APX) were significantly elevated in the wild type, but were not induced or decreased in the mutant. Through transcriptome sequencing analysis and quantitative real-time PCR (qRT-PCR), it was found that when RKNs infect plants, the key genes of jasmonic acid (JA) synthesis, CsAOC and CsAOS, as well as the key gene of the antioxidant system, CsPOD, were all significantly induced. Nevertheless, this induction effect disappeared in the hy5 mutant. Generally, CsHY5 plays a role in the response of cucumber to RKNs, and its deletion increases the sensitivity of cucumber to RKNs. These results suggest that CsHY5 may affect the resistance of cucumber to RKNs by affecting antioxidant enzyme activities and hormone content. Full article

► Show Figures

Figure 1

18 pages, 4846 KiB

Open AccessArticle

The Nrf2 Activator CDDO-Imidazole Suppresses Inflammation-Induced Red Blood Cell Alloimmunization

by Che-Yu Chang, Rosario Hernández-Armengol, Kausik Paul, June Young Lee, Karina Nance, Tomohiro Shibata, Peibin Yue, Christian Stehlik and David R. Gibb

Antioxidants 2025, 14(6), 678; https://doi.org/10.3390/antiox14060678 - 3 Jun 2025

Abstract

Experimental Objective: During red blood cell (RBC) transfusion, inflammation promotes the production of anti-RBC alloantibodies that can cause significant hemolytic events. Avoiding RBC antigen exposure is the only strategy to prevent RBC alloimmunization in transfusion recipients. Identifying mechanisms that inhibit alloimmunization may lead [...] Read more.

Experimental Objective: During red blood cell (RBC) transfusion, inflammation promotes the production of anti-RBC alloantibodies that can cause significant hemolytic events. Avoiding RBC antigen exposure is the only strategy to prevent RBC alloimmunization in transfusion recipients. Identifying mechanisms that inhibit alloimmunization may lead to novel prophylactic interventions. One potential regulatory mechanism is the activation of the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), a master regulator of antioxidant pathways. Pharmacologic Nrf2 activators induce antioxidant production and improve the sequelae of inflammatory diseases. Thus, we tested the hypothesis that a Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]-imidazole (CDDO-Im), regulates inflammation-induced RBC alloimmunization. Methods: WT and Nrf2-deficient mice were treated with inflammatory stimuli and CDDO-Im prior to transfusion with RBCs expressing the KEL antigen (KEL+ RBCs). Anti-KEL IgM and IgG were measured in the serum of transfused mice. Nrf2-activated gene expression and interferon activity were measured in mice and human macrophages pre-treated with CDDO-Im and interferon stimuli. Results: Here, we report that CDDO-Im induces Nrf2-activated gene expression and inhibits type 1 interferon activity, which promotes RBC alloimmunization in transfusion models. In mice transfused with KEL+ RBCs, pre-treatment with CDDO-Im inhibited inflammation-induced anti-KEL antibody production and increased the post-transfusion recovery of KEL+ RBCs in a Nrf2-dependent manner. CDDO-Im also inhibited RBC alloimmunization in mice with pre-existing inflammation. Conclusions: These results indicate that the activation of the Nrf2 antioxidant pathway regulates RBC alloimmunization to the KEL antigen in a pre-clinical model. If these findings translate to other models and human studies, Nrf2 activators may represent a potential prophylactic intervention to inhibit alloimmunization. Full article

(This article belongs to the Special Issue Blood Cells and Redox Homeostasis in Health and Disease, 2nd Edition)

► Show Figures

Figure 1

19 pages, 2165 KiB

Open AccessArticle

Phytochemical Profile and Antioxidant Properties of Invasive Plants Ailanthus altissima (Mill.) Swingle and Helianthus tuberosus L. in Istria Region, Croatia

by Mirela Uzelac Božac, Danijela Poljuha, Slavica Dudaš, Josipa Bilić, Ivana Šola, Maja Mikulič-Petkovšek and Barbara Sladonja

Antioxidants 2025, 14(6), 677; https://doi.org/10.3390/antiox14060677 - 3 Jun 2025

Abstract

Invasive alien plant species, while ecologically and economically problematic, represent an underutilized source of bioactive phytochemicals with promising phytopharmaceutical applications. This study investigates the LC-DAD-MS phenolic profiles of 70% ethanol and 80% methanol leaf and flower extracts of Ailanthus altissima (Mill.) Swingle and [...] Read more.

Invasive alien plant species, while ecologically and economically problematic, represent an underutilized source of bioactive phytochemicals with promising phytopharmaceutical applications. This study investigates the LC-DAD-MS phenolic profiles of 70% ethanol and 80% methanol leaf and flower extracts of Ailanthus altissima (Mill.) Swingle and Helianthus tuberosus L., collected in the Istria region of Croatia, alongside their antioxidant capacities using ABTS, DPPH, and FRAP assays. Both species exhibited high levels of flavonoids and phenolic acids, with consistently higher concentrations in leaf versus flower tissues and in ethanolic versus methanolic extracts. Strong correlations (r > 0.9) between total phenolics and antioxidant activity confirmed the functional significance of these compounds. With a targeted metabolomics approach, in A. altissima, 51 phenolics were identified in leaves and 47 in flowers, with ellagitannins predominating; vescalagin isomers reached 94 mg/g DW in leaves and 82 mg/g DW in flowers. H. tuberosus extracts contained 34 phenolics in leaves and 33 in flowers, with hydroxycinnamic acids and flavonols dominating; 5-caffeoylquinic acid was the principal compound (25 mg/g DW in leaves, 2 mg/g DW in flowers). The identified phytochemicals are known for their potent antioxidant, anti-inflammatory, anticancer, antimicrobial, and metabolic-regulating properties. Additionally, four leaf-specific compounds were identified in each species, indicating potential for targeted extraction. These findings advance the phytochemical characterization of invasive taxa and highlight their potential as sources of natural antioxidants for functional food and pharmaceutical development. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

► Show Figures

Figure 1

19 pages, 1032 KiB

Open AccessArticle

Red Beetroot Skin Powder Addition as a Multifunctional Ingredient in Nougat

by Oana Emilia Constantin, Silvia Lazăr (Mistrianu), Florina Stoica, Roxana Nicoleta Rațu, Doina Georgeta Andronoiu, Nicoleta Stănciuc, Marija Banožić, Nada Ćujić Nikolić, Zorana Mutavski and Gabriela Râpeanu

Antioxidants 2025, 14(6), 676; https://doi.org/10.3390/antiox14060676 - 1 Jun 2025

Abstract

Beetroot (Beta vulgaris L.) is a plant grown for its roots, which are used to obtain sugar, feed animals, and for human use. Beetroot skin, a by-product of food processing, is a significant source of bioactive compounds, including dietary fiber and antioxidants. [...] Read more.

Beetroot (Beta vulgaris L.) is a plant grown for its roots, which are used to obtain sugar, feed animals, and for human use. Beetroot skin, a by-product of food processing, is a significant source of bioactive compounds, including dietary fiber and antioxidants. The primary objective of this work was to utilize beetroot skin powder to produce value-added nougat. Analytical methods, like antioxidant activity tests, proximate analysis, and sensory assessments, are used to determine the impact of beetroot skin powder on the final product. The beetroot skin powder extract had a remarkable content of phytochemicals and antioxidant activity. The inhibitory effect of the extract was tested on enzymes linked to metabolic syndrome, oxidative stress, and inflammation. The beetroot skin powder extract inhibited α-glucosidase, α-amylase, lipase, and lipoxygenase enzymes. The characterization of value-added nougat illustrates the multifunctionality of beetroot peel powder within its composition, serving as a significant source of natural compounds with antioxidant, coloring, and flavoring properties. This enhances sensory attributes, including color, aroma, and texture, augmenting product diversity and consumer appeal. This is evidenced by the increase in the total content of betalains (3.77 ± 0.09 mg/g DW.) and polyphenols (69.48 ± 2.88 mg GAE/100 g DW.), which lead to high antioxidant activity (73.89 ± 3.65 mM Trolox/100 g DW.) for the nougat sample with 6% added beetroot powder. Thus, beetroot skin powder replaced chemically synthesized additives with antioxidants and natural pigments, improving life quality and implicitly capitalizing on beetroot processing by-products, supporting circular economy principles at the global level. Full article

(This article belongs to the Special Issue Valorization of the Antioxidant Power of Natural Compounds)

► Show Figures

Figure 1

Journal Description

Antioxidants

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI