Studies on Antioxidants and Anti-Aging Substances Using Model Organisms and Cell Cultures

A Special Issue of Antioxidants (ISSN 2076-3921) belonging to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 1266

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Guest Editor
Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-0962, Japan
Interests: drosophila; antioxidants; oxidative stress response; Nrf2; autophagy; hemocytes; tumors; innate immunity; cell division
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Special Issue Information

Dear Colleagues,

Some anti-aging substances, which extend the lifespan of organisms or delay the onset of age-related phenomena, have shown the ability to prevent oxidative damage to biomaterials within cells. Other health-promoting substances and natural products have been demonstrated to enhance the removal of damaged proteins and organelles, thereby preventing their accumulation in the cells. These substances are expected to prevent the decline of biological functions and could ultimately delay the progression of aging. Although cultured cells have primarily been used to search for compounds and natural products with such effects and to analyze their mechanisms of action, many identified substances are not digested or absorbed when administered to organisms. For this reason, screenings are also conducted using experimental animals to identify substances with antioxidant and anti-aging effects. However, it is time-consuming and expensive to use mammalian models. In contrast, utilizing nematode and Drosophila models facilitate efficient research and analysis in mechanisms of action in a shorter time frame. More recently, studies have begun to use 3D models of cultured cells and organoids, which mimic tissues. For this Special Issue, we welcome research papers that explore substances and natural products with antioxidant and anti-aging effects, as well as works that elucidate the mechanisms of these effects, using living organisms and organoids. High-quality papers dealing with the screening and analysis of action mechanisms using cultured cells are also acceptable.

Prof. Dr. Yosihhiro H. Inoue
Guest Editor

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Keywords

  • antioxidants
  • anti-aging substances and natural products
  • experimental animals
  • 3D cell culture models
  • organoids
  • acting mechanisms
  • antioxidant genes
  • autophagy
  • proteasome

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Published Papers (1 paper)

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Research

28 pages, 13369 KB  
Article
Metabolic Reprogramming Associated with Ferroptosis Protection by an Indole-Based Antioxidant in Aβ(25–35)-Treated SH-SY5Y Cells
by Mariapia Vietri, Enza Napolitano, Maria Rosaria Miranda, Carmen Marino, Simona Musella, Veronica Di Sarno, Carmine Ostacolo, Michele Manfra, Pietro Campiglia, Mario Felice Tecce, Anna Maria D’Ursi, Ornella Moltedo, Alessia Bertamino, Tania Ciaglia and Vincenzo Vestuto
Antioxidants 2026, 15(7), 798; https://doi.org/10.3390/antiox15070798 - 26 Jun 2026
Viewed by 639
Abstract
Ferroptosis has emerged as a critical mechanism linking iron dysregulation, oxidative stress, and neurodegeneration in amyloid-associated pathologies. Building on our previous work, which identified compound 20 as a promising antioxidant and neuroprotective agent, the present study investigates the molecular mechanisms underlying its protective [...] Read more.
Ferroptosis has emerged as a critical mechanism linking iron dysregulation, oxidative stress, and neurodegeneration in amyloid-associated pathologies. Building on our previous work, which identified compound 20 as a promising antioxidant and neuroprotective agent, the present study investigates the molecular mechanisms underlying its protective activity against amyloid-induced ferroptosis in human neuroblastoma SH-SY5Y cells exposed to Aβ(25–35). Compound 20 (3-(((4-hydroxybenzyl)(methyl)amino)methyl)-1-methyl-N-(2-(piperazin-1-yl)ethyl)-1H-indole-5-carboxamide) markedly counteracted Aβ(25–35)-induced ferroptotic damage by restoring intracellular glutathione levels, depleting the labile iron pool, and suppressing lipid peroxidation. In parallel, the compound significantly rescued mitochondrial membrane potential and attenuated endoplasmic reticulum (ER) expansion associated with ER stress, thereby preserving cellular homeostasis under oxidative challenge. These protective effects were further corroborated by real-time PCR analysis, which revealed the modulation of key genes involved in the oxidative stress response, endoplasmic reticulum stress, and inflammatory pathways. To gain a systems-level insight into these mechanisms, untargeted 1H-NMR metabolomic profiling was performed. This analysis confirmed the activation of antioxidant pathways and disclosed a significant modulation of energy metabolism and GABA-related pathways, both of which are closely linked to redox balance and neuronal resilience. Overall, these findings demonstrate that compound 20 drives metabolic reprogramming that orchestrates its multifactorial protective effect against Aβ(25–35)-induced ferroptosis by coordinating antioxidant defense, iron homeostasis, and ER stress mitigation. Full article
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