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: 22 December 2025 | Viewed by 2687

Special Issue Editors


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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

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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
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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

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Keywords

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

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Published Papers (3 papers)

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Research

20 pages, 23873 KiB  
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
Viewed by 190
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 KiB  
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
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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 KiB  
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 1 | Viewed by 1445
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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