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Antioxidants
Special Issues
Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment
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Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 16774

Special Issue Editors

Dr. Marcello Chieppa

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Guest Editor
Department of Experimental Medicine, University of Salento, 73100 Lecce, Italy
Interests: inflammatory bowel disease; muocsal immunology; inflammation; nutrition; polyphenols
Dr. Angelo Santino

E-Mail Website
Guest Editor
Institute of Science of Food Production, C.N.R. Unit of Lecce, 73100 Lecce, Italy
Interests: biofortification; biotechnology; gut health; plant polyphenols; nutrition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a multifactorial disorder characterized by chronic inflammation and altered gut barrier function. IBD etiopathogenesis is still debated, with several possible triggers converging to similar pathological effects. During the last few decades, numerous discoveries have contributed to elucidating the role of the mucosal immune response, the importance of the gut barrier and the mucus layer integrity and the role of the intestinal microbiota. Despite this progress and the increasing number of pharmacological options, IBD patients still suffer from frequent disease relapse and an important percentage of patients do not respond to treatment, including biological drugs. Increased reactive oxygen species generation (oxidative stress) is a condition associated with IBD pathogenesis and disease relapse. Adjuvant therapies targeting oxidative stress remain limited, despite the numerous reports suggesting their potential beneficial effects in preclinical and clinical research.

The purpose of this Special Issue is to review the current state of the art regarding antioxidant development and clinical/pre-clinical translation in the context of inflammatory bowel disease onset, treatment and remission maintenance. Prevention of IBD-related complication, particularly colon rectal cancer, will also be taken into deep consideration.

Dr. Marcello Chieppa
Dr. Angelo Santino
Guest Editors

Manuscript Submission Information

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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. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • IBD
  • antioxidant
  • gut barrier
  • inflammation
  • natural compounds
  • microbiome
  • colon cancer
  • adjuvant
  • nutritional bioactive products
  • polyphenols

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Published Papers (7 papers)

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Research

Jump to: Review

20 pages, 4202 KB  
Article
Activation of the Nrf2 Signaling Pathway by a Ginseng–Salvia Root–Notoginseng Composite Alleviates Ulcerative DSS-Induced Colitis via Restoring Gut Microbiota and the Intestinal Barrier
by Xinao Lyu, Liurong Zhang, Jia Si, Shasha Dai, Huaiyu Su, Shuhuan Lyu, Lin Chen, Jianwei Sun, Xiangqun Jin and Haiyan Li
Antioxidants 2026, 15(3), 320; https://doi.org/10.3390/antiox15030320 - 4 Mar 2026
Viewed by 931
Abstract
Current treatments for ulcerative colitis (UC) often fail to adequately address its multifactorial pathogenesis, which involves oxidative stress, barrier dysfunction, and gut microbiota dysbiosis. This study evaluated the therapeutic potential and multi-targeting mechanism of a ginseng, salvia root, and notoginseng oral solution (GSNS) [...] Read more.
Current treatments for ulcerative colitis (UC) often fail to adequately address its multifactorial pathogenesis, which involves oxidative stress, barrier dysfunction, and gut microbiota dysbiosis. This study evaluated the therapeutic potential and multi-targeting mechanism of a ginseng, salvia root, and notoginseng oral solution (GSNS) in a mouse model of colitis induced by dextran sulfate sodium (DSS). Based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology, 25 major bioactive components were identified. Following the induction of colitis with 3.5% DSS in C57BL/6J mice, the animals were treated with the GSNS (40, 80, or 160 mg/kg/day) or 5-Amino Salicylic Acid (5-ASA). The therapeutic efficacy was assessed via disease activity, histopathological staining, cytokines and oxidative stress analysis, and a barrier integrity test. Combined data from Western blot, qPCR, immunohistochemistry, electron microscopy, and 16S rRNA sequencing indicate that the therapeutic effect of the GSNS against colitis is attributable to its dual role in dampening pro-inflammatory cytokines and potentiating antioxidant defenses via the Nrf2/HO-1 signaling pathway. It also upregulated Occludin expression, repaired tight junctions, and was associated with beneficial alterations in the gut microbiota, as evidenced by increased Prevotellaceae and suppressing Escherichia-Shigella. These findings demonstrated that the GSNS exerts a multi-target effect against colitis by synergistically enhancing antioxidant defense, repairing the intestinal barrier, and modulating microbial ecology, supporting its potential as a promising natural compound-based candidate for DSS-induced colitis treatment. Full article
(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)
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24 pages, 8489 KB  
Article
DUOX2-Driven Oxidative Stress Alters the Gut Redox Niche and Promotes Microbial Dysbiosis in Crohn’s Disease
by Shu Xu, Xiaozhi Li, Xueting Wu, Kangrong Zheng, Youcai Yi, Yuqi Lin, Chunyang Tian, Yijun Zhu, Ce Tang, Shixian Hu, Shenghong Zhang, Yao He, Minhu Chen and Rui Feng
Antioxidants 2026, 15(3), 292; https://doi.org/10.3390/antiox15030292 - 26 Feb 2026
Viewed by 1658
Abstract
Crohn’s disease (CD) is characterized by chronic intestinal inflammation accompanied by gut dysbiosis and redox imbalance. We investigated the role of dual oxidase-2 (DUOX2), a major epithelial source of reactive oxygen species (ROS), in linking oxidative stress to microbe–host crosstalk. DUOX2 expression was [...] Read more.
Crohn’s disease (CD) is characterized by chronic intestinal inflammation accompanied by gut dysbiosis and redox imbalance. We investigated the role of dual oxidase-2 (DUOX2), a major epithelial source of reactive oxygen species (ROS), in linking oxidative stress to microbe–host crosstalk. DUOX2 expression was upregulated in human intestinal samples and was positively associated with inflammatory readouts, oxidative stress indices, and dysbiosis. Intestinal epithelial cell-specific Duox2 knockout (KO) mice exhibited reduced mucosal ROS, preserved barrier integrity, and attenuated dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Cohousing and fecal microbiota transplantation demonstrated that this protective phenotype was microbiota-dependent. Multi-omics profiling identified enrichment of Parabacteroides, particularly P. distasonis, in Duox2 KO mice, and oral supplementation with P. distasonis enhanced resistance to colitis. Mechanistically, DUOX2-derived oxidative stress constrained Parabacteroides growth, as P. distasonis displayed marked susceptibility to hydrogen peroxide, with excessive intracellular ROS accumulation and an absence of key antioxidant defenses—including peroxide reductase C (AhpC) and superoxide dismutase B (SodB)—indicating that epithelial DUOX2 shapes a hostile luminal redox niche unfavorable to these beneficial microbes. Pharmacological inhibition of DUOX2 with Compound 521 reduced oxidative stress, ameliorated colitis, and partially restored microbial balance. These findings establish a DUOX2–ROS–microbiota axis in which epithelial DUOX2 amplifies oxidative stress, remodels the gut ecosystem, and promotes inflammation, and highlights DUOX2 suppression or ROS-sensitive Parabacteroides as potential redox-centric therapeutic strategies for CD. Full article
(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)
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35 pages, 13715 KB  
Article
Engineered Sporopollenin Exine Capsules for Colon-Targeted Delivery and Antioxidant Therapy of Pogostemon Oil in Ulcerative Colitis
by Jia Si, Shasha Dai, Huaiyu Su, Zhongjuan Ji, Cong Dong, Xinao Lyu, Shuhuan Lyu, Lin Chen, Jianwei Sun, Xiangqun Jin and Haiyan Li
Antioxidants 2026, 15(1), 116; https://doi.org/10.3390/antiox15010116 - 16 Jan 2026
Viewed by 866
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease associated with oxidative stress. Pogostemon oil (PO) exhibits potent antioxidant and anti-inflammatory activities but is limited by high volatility and poor gastrointestinal stability. In this study, sporopollenin exine capsules (SECs) were engineered as natural micro-carriers [...] Read more.
Ulcerative colitis (UC) is an inflammatory bowel disease associated with oxidative stress. Pogostemon oil (PO) exhibits potent antioxidant and anti-inflammatory activities but is limited by high volatility and poor gastrointestinal stability. In this study, sporopollenin exine capsules (SECs) were engineered as natural micro-carriers for PO, achieving efficient encapsulation (η > 69%) and a high adsorption capacity (27.64 g/g). A pH-sensitive calcium alginate shell was subsequently applied to construct colon-targeted microspheres (Ca-Alg@PO-SECs). The resulting system improved the thermal and photostability of PO. In vitro dissolution assays confirmed the system’s pH-responsiveness, maintaining integrity under simulated gastric conditions while enabling localized release at intestinal pH. In a DSS-induced acute UC mouse model, Ca-Alg@PO-SECs effectively alleviated clinical symptoms, as evidenced by improved body weight, colon length, and disease activity index. At the inflammatory level, the formulation modulated key cytokines (IL-1β, IL-6, and IL-10). Overall, Ca-Alg@PO-SECs provides a biocompatible, colon-targeted delivery strategy that preserves the bioactivity of essential oils and offers a promising preclinical approach for localized UC therapy. Full article
(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)
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20 pages, 23873 KB  
Article
Engeletin Targets Mitochondrial Dysfunction to Attenuate Oxidative Stress and Experimental Colitis in Intestinal Epithelial Cells Through AMPK/SIRT1/PGC-1α Signaling
by Jing Li, Zhijun Geng, Lixia Yin, Ju Huang, Minzhu Niu, Keni Zhang, Xue Song, Yueyue Wang, Lugen Zuo and Jianguo Hu
Antioxidants 2025, 14(5), 524; https://doi.org/10.3390/antiox14050524 - 27 Apr 2025
Cited by 10 | Viewed by 2550
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired mitochondrial homeostasis in intestinal epithelial cells (IECs) disrupts redox [...] Read more.
Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired mitochondrial homeostasis in intestinal epithelial cells (IECs) disrupts redox balance, exacerbates oxidative stress, and triggers apoptosis, further compromising barrier integrity. This study investigated the therapeutic effects of Engeletin (Eng), a dihydroflavonoid from Smilax glabra Roxb., in dextran sulfate sodium (DSS)-induced colitis mice and colonic organoid models. Eng administration (10, 20, 40 mg/kg) significantly alleviated colitis symptoms, including weight loss, disease activity index (DAI) scores, and colon shortening, while restoring intestinal barrier integrity through the upregulation of tight junction proteins (ZO-1, claudin-1) and goblet cell preservation. Eng suppressed NF-κB-mediated inflammation and activated the Nrf2 antioxidant pathway, as well as reduced oxidative stress markers (MDA, CAT, GSH, and SOD). It attenuated epithelial apoptosis by balancing pro- and anti-apoptotic proteins (Bax/Bcl2, c-caspase3) and ameliorated mitochondrial dysfunction via enhanced ATP production, mtDNA levels, and complex I/IV activity. Mechanistically, Eng activated the AMPK/SIRT1/PGC-1α axis, and pharmacological inhibition of PGC-1α abolished its mitochondrial protective and anti-apoptotic effects. These findings demonstrate that Eng alleviates colitis by targeting mitochondrial homeostasis and oxidative stress through AMPK/SIRT1/PGC-1α signaling, offering a multitargeted strategy for IBD therapy. Full article
(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)
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22 pages, 2019 KB  
Article
A Diet Fortified with Anthocyanin-Rich Extract (RED) Reduces Ileal Inflammation in a Senescence-Prone Mice Model of Crohn’s-Disease-like Ileitis
by Giulio Verna, Vicky Caponigro, Stefania De Santis, Emanuela Salviati, Fabrizio Merciai, Fabiano De Almeida Celio, Pietro Campiglia, Katia Petroni, Chiara Tonelli, Aurelia Scarano, Angelo Santino, Manuela Giovanna Basilicata, Marcello Chieppa and Fabio Cominelli
Antioxidants 2025, 14(4), 473; https://doi.org/10.3390/antiox14040473 - 15 Apr 2025
Cited by 2 | Viewed by 1843
Abstract
SAMP mice develop progressive Crohn’s disease (CD)-like ileitis without spontaneous colitis that worsens over time without chemical, genetic, or immunological manipulation. Even growing in an identical vivarium and fed with the same diet, SAMP mice reveal a distinct fecal microbiome, metabolome, and lipidome [...] Read more.
SAMP mice develop progressive Crohn’s disease (CD)-like ileitis without spontaneous colitis that worsens over time without chemical, genetic, or immunological manipulation. Even growing in an identical vivarium and fed with the same diet, SAMP mice reveal a distinct fecal microbiome, metabolome, and lipidome profile compared to AKR mice, their non-inflamed parental control strain. Differences are already present in 5-week-old mice, with a tendency to increase in 15-week-old mice. SAMP and AKR mice metabolome and lipidome profiles were substantially different, belonging to two clusters in line with the progression of intestinal disease. Similarly, the 16S analysis confirmed differences between 15-week-old AKR and SAMP mice. The protective role of dietary polyphenols has been documented in inflammatory bowel diseases (IBD); thus, we supplemented the chow diet with an anthocyanin-rich extract (RED) to evaluate disease reduction in SAMP mice and changes in fecal microbiota/metabolome. Our data reveal that 10-week supplementation with anthocyanin-rich extract ameliorated disease severity in SAMP mice despite limited fecal microbiota/metabolome differences. Full article
(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)
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19 pages, 3857 KB  
Article
Biological Response of Treatment with Saffron Petal Extract on Cytokine-Induced Oxidative Stress and Inflammation in the Caco-2/Human Leukemia Monocytic Co-Culture Model
by Federica De Cecco, Sara Franceschelli, Valeria Panella, Maria Anna Maggi, Silvia Bisti, Arturo Bravo Nuevo, Damiano D’Ardes, Francesco Cipollone and Lorenza Speranza
Antioxidants 2024, 13(10), 1257; https://doi.org/10.3390/antiox13101257 - 17 Oct 2024
Cited by 7 | Viewed by 3119
Abstract
The pathogenesis of Inflammatory Bowel Disease (IBD) involves complex mechanisms, including immune dysregulation, gut microbiota imbalances, oxidative stress, and defects in the gastrointestinal mucosal barrier. Current treatments for IBD often have significant limitations and adverse side effects, prompting a search for alternative therapeutic [...] Read more.
The pathogenesis of Inflammatory Bowel Disease (IBD) involves complex mechanisms, including immune dysregulation, gut microbiota imbalances, oxidative stress, and defects in the gastrointestinal mucosal barrier. Current treatments for IBD often have significant limitations and adverse side effects, prompting a search for alternative therapeutic strategies. Natural products with anti-inflammatory and antioxidant properties have demonstrated potential for IBD management. There is increasing interest in exploring food industry waste as a source of bioactive molecules with healthcare applications. In this study, a co-culture system of Caco-2 cells and PMA-differentiated THP-1 macrophages was used to simulate the human intestinal microenvironment. Inflammation was induced using TNF-α and IFN-γ, followed by treatment with Saffron Petal Extract (SPE). The results demonstrated that SPE significantly attenuated oxidative stress and inflammation by downregulating the expression of pro-inflammatory mediators such as iNOS, COX-2, IL-1β, and IL-6 via modulation of the NF-κB pathway. Given that NF-κB is a key regulator of macrophage-driven inflammation, our findings support further investigation of SPE as a potential complementary therapeutic agent for IBD treatment. Full article
(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)
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Review

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31 pages, 1124 KB  
Review
Selenium: A Key Element in Inflammatory Bowel Disease
by Francesca Gorini and Alessandro Tonacci
Antioxidants 2025, 14(11), 1299; https://doi.org/10.3390/antiox14111299 - 29 Oct 2025
Cited by 4 | Viewed by 4304
Abstract
Inflammatory bowel disease (IBD) is a multifactorial and complex condition of the gastrointestinal tract shaped by host genetics, immune dysregulation, gut microbiota and environmental determinants, with a steadily rising global prevalence. Although the etiology of IBD remains incompletely understood, chronic inflammation accompanied by [...] Read more.
Inflammatory bowel disease (IBD) is a multifactorial and complex condition of the gastrointestinal tract shaped by host genetics, immune dysregulation, gut microbiota and environmental determinants, with a steadily rising global prevalence. Although the etiology of IBD remains incompletely understood, chronic inflammation accompanied by oxidative stress, immune dysregulation, and gut dysbiosis is widely recognized as a hallmark of the condition. Given the frequent occurrence of undernutrition in IBD patients, the role of vitamins and micronutrients in modulating disease activity has been recently explored. Selenium (Se) is universally recognized as an essential trace element due to its diverse physiological functions, including potent antioxidant activity, anti-inflammatory effects, immunomodulatory properties, and the ability to influence gut microbial composition and diversity. This comprehensive review examines current evidence on the relationship between Se status and IBD, integrating epidemiological and experimental findings, elucidating the underlying biological mechanisms, and introducing Se nanoparticles, a viable therapeutic option using Se in IBD management. Full article
(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)
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