AntioxidantsPub Date : 2025-06-20DOI: 10.3390/antiox14070758
Hsin Hsueh Shen, Stephen J Peterson, Lars Bellner, Abu Choudhary, Lior Levy, Leah Gancz, Ariel Sasson, Joseph Trainer, Rita Rezzani, Abraham Resnick, David E Stec, Nader G Abraham
{"title":"RETRACTED: Shen et al. Cold-Pressed <i>Nigella Sativa</i> Oil Standardized to 3% Thymoquinone Potentiates Omega-3 Protection against Obesity-Induced Oxidative Stress, Inflammation, and Markers of Insulin Resistance Accompanied with Conversion of White to Beige Fat in Mice. <i>Antioxidants</i> 2020, <i>9</i>, 489.","authors":"Hsin Hsueh Shen, Stephen J Peterson, Lars Bellner, Abu Choudhary, Lior Levy, Leah Gancz, Ariel Sasson, Joseph Trainer, Rita Rezzani, Abraham Resnick, David E Stec, Nader G Abraham","doi":"10.3390/antiox14070758","DOIUrl":"10.3390/antiox14070758","url":null,"abstract":"<p><p>The journal retracts the article \"Cold Press Nigella Sativa oil standardized to 3%, thymoquinone Potentiates Omega-3 Protection against Obesity-Induced Oxidative Stress, Inflammation and Insulin Resistance via Conversion of White to Beige Fat in Mice\" [...].</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Puerarin as a Phytochemical Modulator of Gastrointestinal Homeostasis in Livestock: Molecular Mechanisms and Translational Applications.","authors":"Jiehong Zhou, Jianyu Lv, Xin Chen, Tian Li, Jianzhong Shen, Zhanhui Wang, Chongshan Dai, Zhihui Hao","doi":"10.3390/antiox14060756","DOIUrl":"10.3390/antiox14060756","url":null,"abstract":"<p><p>The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body's largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of the intestine is paramount for ensuring animal health and productivity. Puerarin, a naturally derived isoflavonoid from the <i>Pueraria</i> species, exhibits multifaceted bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Emerging evidence highlights puerarin's capacity to enhance gut health in farm animals through four pivotal mechanisms: (1) optimization of intestinal morphology via crypt-villus architecture remodeling, (2) augmentation of systemic and mucosal antioxidant defenses through Nrf2/ARE pathway activation, and (3) reinforcement of intestinal barrier function by regulating tight junction proteins (e.g., ZO-1, occludin), mucin secretion, intestinal mucosal immune barrier, the composition of microbiota, and the derived beneficial metabolites; (4) regulating the function of the intestinal nervous system via reshaping the distribution of intestinal neurons and neurotransmitter secretion function. This review synthesizes current knowledge on puerarin's protective effects on intestinal physiology in farm animals, systematically elucidates its underlying molecular targets (including TLR4/NF-κB, MAPK, and PI3K/Akt signaling pathways), and critically evaluates its translational potential in mitigating enteric disorders such as post-weaning diarrhea and inflammatory bowel disease in agricultural practices.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-19DOI: 10.3390/antiox14060755
Marko D Prokić, Marcelo Hermes-Lima, Daniel C Moreira
{"title":"Redox Metabolism in Ecophysiology and Evolution, 2nd Edition.","authors":"Marko D Prokić, Marcelo Hermes-Lima, Daniel C Moreira","doi":"10.3390/antiox14060755","DOIUrl":"10.3390/antiox14060755","url":null,"abstract":"<p><p>The ability of organisms to regulate the production of reactive oxygen and nitrogen species (RONS), manage pro-oxidant activity, and make use of redox pathways has significantly influenced their evolution [...].</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemical Composition and Antioxidant Activity of Prokupac Grape Pomace Extract: Implications for Redox Modulation in Honey Bee Cells.","authors":"Uroš Glavinić, Đura Nakarada, Jevrosima Stevanović, Uroš Gašić, Marko Ristanić, Miloš Mojović, Zoran Stanimirović","doi":"10.3390/antiox14060751","DOIUrl":"10.3390/antiox14060751","url":null,"abstract":"<p><p>There is a growing interest in using agri-food by-products and a demand for natural substances that might help maintain healthy honey bee colonies. We investigated a by-product of the wine industry, a grape pomace (GP) of the autochthonous Prokupac grape cultivar from Serbia. A hydroethanolic extract (50% (<i>w</i>/<i>v</i>) ethanol) of GP (Prokupac GP extract) obtained by the pressurized liquid extraction (PLE) method was subjected to qualitative profiling of phenolic composition by liquid chromatography with OrbiTrap Exploris 120 mass spectrometer. Then, the extracts' antioxidant and redox-modulatory activities were evaluated through Electron Paramagnetic Resonance (EPR) spectroscopy. Finally, the extract's potential to modulate cellular redox status was evaluated using cultured AmE-711 honey bee cells. The results show that the Prokupac GP extract contains a wide array of flavonoids, anthocyanins, stilbenes, and their various conjugated derivatives and that anthocyanins, particularly malvidin-based compounds, dominate. EPR measurements showed strong scavenging activity against superoxide anion (O<sub>2</sub><sup>•-</sup>) and hydroxyl radicals (<sup>•</sup>OH), with inhibition efficiencies of 84.37% and 81.81%, respectively, while activity against the DPPH radical was lower (17.75%). In the cell-based assay, the Prokupac GP extract consistently provided strong antioxidant protection and modulated the cellular response to oxidative stress by over 14%. In conclusion, while the Prokupac GP extract demonstrated antioxidant properties and the ability to modulate cellular responses to oxidative stress, in vivo studies on honey bees are required to confirm its efficacy and safety for potential use in beekeeping practice.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-18DOI: 10.3390/antiox14060753
Maria D'Elia, Carmen Marino, Rita Celano, Enza Napolitano, Chiara Colarusso, Rosalinda Sorrentino, Anna Maria D'Ursi, Luca Rastrelli
{"title":"Impact of a Formulation Containing Chaga Extract, Coenzyme Q10, and Alpha-Lipoic Acid on Mitochondrial Dysfunction and Oxidative Stress: NMR Metabolomic Insights into Cellular Energy.","authors":"Maria D'Elia, Carmen Marino, Rita Celano, Enza Napolitano, Chiara Colarusso, Rosalinda Sorrentino, Anna Maria D'Ursi, Luca Rastrelli","doi":"10.3390/antiox14060753","DOIUrl":"10.3390/antiox14060753","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored cell metabolism and its activity as an antioxidant, using a combination of NMR-based metabolomics and UHPLC-HRMS analytical techniques.</p><p><strong>Methods: </strong>SH-SY5Y neuroblastoma cells were treated with RP-25, and cell viability was assessed via CCK-8 assay. Metabolomic profiles of the treated and untreated cells were analyzed by 1D-NMR, providing insights into both intracellular metabolites (endometabolome) and excreted metabolites (exometabolome). Additionally, a UHPLC-HRMS method was developed for quality control and analysis of the RP-25 formulation. Multivariate statistical approaches, including PLS-DA and volcano plot analyses, were used to identify key metabolic changes. Changes in mitochondrial membrane potential were assessed by means of TMRE assay, while radical oxygen species (ROS) were measured by means of the DCHF assay.</p><p><strong>Results: </strong>RP-25 treatment did not affect cell viability but significantly increased metabolic pathways, including amino acid biosynthesis, oxidative phosphorylation, and glycolysis. Higher levels of ATP, glutamate, tyrosine, and proline were observed in treated cells than in control cells, indicating enhanced cellular energy production, as also proved by the increased stability of the mitochondrial membrane after RP-25 treatment, an index of preserved mitochondrial functions. In support, the formulation RP-25 showed antioxidant activity when cells underwent peroxide oxygen stimulation. This effect was mainly due to the combination of Chaga, CoQ10, and ALA, main components of the RP25 formulation. Moreover, the analysis of enriched pathways highlighted that RP formulation influenced mitochondrial energy and oxidative stress response.</p><p><strong>Conclusions: </strong>RP-25 demonstrated biological activity in that it mitigated mitochondrial dysfunction and oxidative stress in neuronal cells, with potential implications in neuronal diseases associated with dysfunctional mitochondria.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-18DOI: 10.3390/antiox14060754
Meijun Zeng, Yang Li, Jie Cheng, Jingyu Wang, Qiyu Liu
{"title":"Prebiotic Oligosaccharides in Skin Health: Benefits, Mechanisms, and Cosmetic Applications.","authors":"Meijun Zeng, Yang Li, Jie Cheng, Jingyu Wang, Qiyu Liu","doi":"10.3390/antiox14060754","DOIUrl":"10.3390/antiox14060754","url":null,"abstract":"<p><p>Prebiotic oligosaccharides have attracted significant interest in dermatology and skin health due to their ability to modulate the skin microbiome and microbiota-host interactions. This review offers a novel dual perspective, systematically examining the benefits of both oral intake and topical application of prebiotic oligosaccharides, including well-established prebiotics (e.g., human milk oligosaccharides, galacto- and fructo-oligosaccharides) and emerging prebiotic candidates (e.g., gluco-oligosaccharides, chitosan-oligosaccharides, agaro-oligosaccharides). First, cutting-edge synthetic processes for producing diverse oligosaccharides and their structural chemistry are introduced. Then, we discuss in vitro studies demonstrating their efficacy in promoting skin commensals, inhibiting pathogens, and conferring protective effects, such as antioxidant, anti-inflammatory, anti-melanogenic, and wound-healing properties. Furthermore, we emphasize in vivo animal studies and clinical trials revealing that prebiotic oligosaccharides, administered orally or topically, alleviate atopic dermatitis, enhance skin hydration, attenuate acne, and protect against photo-aging by modulating skin-gut microbiota and immune responses. Mechanistically, we integrate genetic and molecular insights to elucidate how oligosaccharides mediate these benefits, including gut-skin axis crosstalk, immune regulation, and microbial metabolite signaling. Finally, we highlight current commercial applications of oligosaccharides in cosmetic formulations while addressing scientific and practical challenges, such as structure-function relationships, clinical scalability, and regulatory considerations. This review bridges mechanistic understanding with practical applications, offering a comprehensive resource for advancing prebiotic oligosaccharides-based skincare therapies.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-18DOI: 10.3390/antiox14060752
Aleksandar Ž Kostić, Aleksandra Sknepnek, Danijel D Milinčić, Uroš Gašić, Sofija Kilibarda, Mirjana B Pešić
{"title":"Influence of Kombucha Fermentation on Antioxidant and Antimicrobial Activity of Monofloral Rapeseed Bee-Collected Pollen.","authors":"Aleksandar Ž Kostić, Aleksandra Sknepnek, Danijel D Milinčić, Uroš Gašić, Sofija Kilibarda, Mirjana B Pešić","doi":"10.3390/antiox14060752","DOIUrl":"10.3390/antiox14060752","url":null,"abstract":"<p><p>Bee-collected pollen (BCP) can serve as an excellent enhancer of functional food bioactivity, particularly when it is fermented. The aim of this study was to prepare a novel kombucha-based beverage (KPE) enriched with fermented monofloral rapeseed (<i>Brassica napus</i> L.) BCP. To characterize the obtained samples, a proximate phytochemical composition analysis (including total phenolic and flavonoid content) was performed, as well as a detailed untargeted UHPLC-Q-ToF-MS profiling of phenolics and phenylamides. To biologically characterize KPE, antioxidant and antimicrobial activities were monitored. The total phenolic and flavonoid content, enhanced by the addition of BCP to the kombucha green tea beverage, was dose-dependent. The control sample showed a strong predominance of flavan-3-ols, distinguishing it from the KPE samples, where flavonol predominance and an increased content of phenolic acids were observed. Notably, the most significant markers of BCP were phenylamides, which were completely absent in the control. Although antioxidant activity was proximately highest in the control sample, KPE samples exhibited significantly improved antimicrobial activity.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-18DOI: 10.3390/antiox14060750
Tao Liu, Chang-Chun Song, Fu-Xuan Duan, Chong-Chao Zhong, Sheng-Zan Liu, Jia-Cheng Guo, An-Gen Yu, Zhi Luo
{"title":"SENP1 Senses Oxidative Stress to Regulate the SUMOylation Modification of ZIP8 and Maintain Zinc Transport Functions.","authors":"Tao Liu, Chang-Chun Song, Fu-Xuan Duan, Chong-Chao Zhong, Sheng-Zan Liu, Jia-Cheng Guo, An-Gen Yu, Zhi Luo","doi":"10.3390/antiox14060750","DOIUrl":"10.3390/antiox14060750","url":null,"abstract":"<p><p>Zinc (Zn) is a crucial trace element in vertebrates, fulfilling a range of physiological functions, whose metabolism and homeostasis are manipulated by Zn transporter proteins. SUMOylation, a reversible post-translational modification (PTM), extensively participates in various biological processes in the body, yet its underlying mechanism in regulating Zn transporters remains unexplored. Our findings indicate that high dietary Zn substantially elevated intestinal Zn content and modulated the expression profiles of Zn transporter-related genes and proteins, including ZIP8 transporter. In addition, high Zn diet tended to inhibit the SUMOylation modification and upregulate deSUMOylation modification in the intestine and intestinal epithelial cells. Furthermore, we found that the ZIP8 protein undergoes SUMOylation modification; UBC9 upregulated but SENP1 and Zn downregulated the SUMOylation level of ZIP8, and the K24 and K222 positions are the primary SUMOylation modification sites of ZIP8 protein in yellow catfish. Mechanistically, SENP1 modulates the deSUMOylation modification of ZIP8 by sensing Zn-induced oxidative stress. In summary, for the first time, we have uncovered a unique regulatory mechanism of ZIP8 mediated by SUMOylation modification in vertebrates and demonstrate that SENP1 is capable of sensing oxidative stress to reduce the SUMOylation modification of ZIP8 at K24 and K222 sites.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-17DOI: 10.3390/antiox14060744
Serena Silvestro, Marco Calabrò, Alessandra Trainito, Stefano Salamone, Federica Pollastro, Emanuela Mazzon, Aurelio Minuti
{"title":"Cannabinol's Modulation of Genes Involved in Oxidative Stress Response and Neuronal Plasticity: A Transcriptomic Analysis.","authors":"Serena Silvestro, Marco Calabrò, Alessandra Trainito, Stefano Salamone, Federica Pollastro, Emanuela Mazzon, Aurelio Minuti","doi":"10.3390/antiox14060744","DOIUrl":"10.3390/antiox14060744","url":null,"abstract":"<p><p><i>Cannabis sativa</i> is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases. Previous research showed that cannabinol (CBN), a minor cannabinoid derived from Δ<sup>9</sup>-tetrahydrocannabinol, exhibits antioxidant, anti-inflammatory, analgesic, and anti-bacterial effects. The objective of this study was to assess the protective potential of 24 h CBN pre-treatment, applied at different concentrations (5 µM, 10 µM, 20 µM, 50 µM, and 100 µM), in differentiated neuroblastoma × spinal cord (NSC-34) cells. Transcriptomic analysis was performed using next-generation sequencing techniques. Our results reveal that CBN had no negative impact on cell viability at the tested concentrations. Instead, it showed a significant effect on stress response and neuroplasticity-related processes. Specifically, based on the Reactome database, the biological pathways mainly perturbed by CBN pre-treatment were investigated. This analysis highlighted a significant enrichment in the Reactome pathway's cellular response to stress, cellular response to stimuli, and axon guidance. Overall, our results suggest that CBN holds promise as an adjuvant agent for neurodegenerative diseases by modulating genes involved in neuronal cell survival and axon guidance.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-17DOI: 10.3390/antiox14060749
Yang Yu, Yali Shan, Jiani Lu, Yexing Xian, Zhengshan Tang, Xinyu Guo, Yan Huang, Xin Ni
{"title":"Ferroptosis and Sterol Biosynthesis Dysregulation in Granulosa Cells of Patients with Diminished Ovarian Reserve.","authors":"Yang Yu, Yali Shan, Jiani Lu, Yexing Xian, Zhengshan Tang, Xinyu Guo, Yan Huang, Xin Ni","doi":"10.3390/antiox14060749","DOIUrl":"10.3390/antiox14060749","url":null,"abstract":"<p><p>Granulosa cell (GC) dysfunction contributes to diminished ovarian reserve (DOR). We collected GC and follicular fluid samples from the patients of normal ovarian reserve (NOR) and DOR. RNA-seq of GCs showed that cholesterol/sterol metabolism and biosynthesis and extracellular matrix organization were enriched in the DOR group. Metabolomics of follicular fluid revealed enrichment in steroid hormone biosynthesis, tryptophan metabolism, and fatty acid β-oxidation in DOR. The apoptosis rate was increased, whereas the proliferative rate was decreased in GCs of DOR. The Prussian blue staining rate was increased whilst GPX4 and SLC7A11 expression were downregulated in GCs of DOR. Mitochondrial morphology displayed the features of ferroptosis in GCs of DOR. FSHR, CYP19A1, NR5A1, and phosphorylated CREB levels were substantially downregulated in GCs, accompanied by increased androgen levels in follicular fluids in DOR. The key factors linked to the mevalonate pathway, HMGCR, SQLE, and SREBF2, were robustly increased in DOR. FSHR and NR5A1 levels were correlated with CYP19A1 levels, whilst CYP19A1 levels were positively correlated with GPX4 and SLC7A11 levels. Our findings indicate ferroptosis and dysregulation of cholesterol/sterol metabolism and biosynthesis occurrence in GCs of DOR, which might be associated with reduced FSHR signaling and decreased conversion of androgen to estrogen.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}