AntioxidantsPub Date : 2026-09-17DOI: 10.3390/antiox15091189
Julia Jaromirska, Piotr Białasiewicz, Dominik Strzelecki, Agata Gabryelska
{"title":"Molecular Drivers of Cognitive Decline and Neuroprotection in Obstructive Sleep Apnea: A Narrative Review.","authors":"Julia Jaromirska, Piotr Białasiewicz, Dominik Strzelecki, Agata Gabryelska","doi":"10.3390/antiox15091189","DOIUrl":"10.3390/antiox15091189","url":null,"abstract":"<p><p>Obstructive sleep apnea is a common sleep disorder characterized by chronic intermittent hypoxia (CIH), sleep fragmentation, and upper-airway collapse. Beyond respiratory issues, OSA significantly impacts the central nervous system, increasing the risk for mild cognitive impairment and dementia. This review synthesizes the dual nature of CIH-induced molecular cascades, describing pathways driving neurodegeneration, such as SUMOylation dysregulation, toll-like receptor signaling, and inflammasome overactivation (largely characterized in experimental and animal CIH models), and those activating endogenous neuroprotective adaptations. Physiological defense mechanisms, such as the upregulation of erythropoietin, shifts toward anaerobic glycolysis, and the activation of neurotrophic factors, may act to mitigate neuronal injury. Rather than acting as independent processes, these molecular responses form a dynamic balance between neuronal injury and endogenous neuroprotection. Here, we introduce the concept of 'neuroprotective reserve' as a novel, hypothesis-generating framework to describe this intrinsic buffering capacity against hypoxic stress. Understanding and clinically validating these pathways is critical for developing early diagnostic biomarkers and targeted adjunctive interventions that complement standard therapy to prevent irreversible neurocognitive decline.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057276","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 : 2026-09-17DOI: 10.3390/antiox15091188
Jingxian Zheng, Yijia Tang, Shu Xing, Weiwei Han
{"title":"Proteome-Scale Discovery and Multilevel Validation of Antioxidant Short Peptides from <i>Apostichopus japonicus</i>: Keap1 Interactions and Cellular Antioxidant Responses.","authors":"Jingxian Zheng, Yijia Tang, Shu Xing, Weiwei Han","doi":"10.3390/antiox15091188","DOIUrl":"10.3390/antiox15091188","url":null,"abstract":"<p><p>Antioxidant peptides from marine proteins are promising bioactive compounds, yet efficient discovery and multilevel validation remain challenging. Here, we established a proteome-scale workflow integrating virtual enzymatic hydrolysis, dual-model antioxidant prediction, consensus ranking, toxicity screening, sequence-diversity-informed selection, experimental validation, and molecular simulation to identify antioxidant short peptides from <i>Apostichopus japonicus</i>. Five newly identified antioxidant short peptides (DHE, HDHE, DDHN, EHED, and QHDE) were synthesized for experimental validation. All showed DPPH and ABTS radical-scavenging activity, good cytocompatibility, and protection against D-galactose-induced loss of HepG2 cell viability. HDHE showed the highest DPPH activity and QHDE showed the highest ABTS activity at higher concentrations, whereas EHED produced the greatest recovery of cell viability. Molecular docking and 100 ns molecular dynamics simulations indicated sequence-dependent Keap1 interaction patterns and preserved global receptor stability, but these computational features did not parallel cytoprotection. Western blotting further showed differential regulation of Keap1, Nrf2, and HO-1, with DDHN, EHED, and QHDE significantly increasing HO-1 expression. Across the workflow, predicted activity, chemical radical scavenging, Keap1 interaction characteristics, and cellular protection did not converge on the same peptide. These findings establish a proteome-scale discovery strategy and show that multilevel validation is essential because computational, chemical, molecular-interaction, and cellular readouts represent complementary rather than interchangeable dimensions of antioxidant peptide performance.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057183","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":"Dietary (Poly)phenol Intake, Inflammatory Biomarkers, and Mild Cognitive Impairment in Italian Adults.","authors":"Margherita Grasso, Francesca L'Episcopo, Giuseppe Toscano, Evelyn Frias-Toral, Stefano Muratore, Maria Angela Tripodi, Sabrina Musso, Veronica Bentivegna, Lucrezia Costanzo, Giusi Fatati, Chiara Mascali, Giorgia Serena Gullotta, Raynier Zambrano-Villacres, Lisandra León Brizuela, Fabio Galvano, Giuseppe Grosso, Justyna Godos, Raffaele Ferri, Giuseppe Lanza, Filippo Caraci","doi":"10.3390/antiox15091181","DOIUrl":"10.3390/antiox15091181","url":null,"abstract":"<p><strong>Background: </strong>Dietary (poly)phenols have been proposed to protect against age-related cognitive decline through antioxidant, anti-inflammatory, and neuroprotective mechanisms. However, evidence specifically addressing mild cognitive impairment (MCI) remains limited. This study investigated the association between habitual dietary (poly)phenol intake, cognitive status, and circulating inflammatory biomarkers in older adults.</p><p><strong>Methods: </strong>In this cross-sectional study, Italian adults aged ≥65 years attending a memory clinic underwent standardized neuropsychological assessment for MCI diagnosis. Habitual dietary intake was assessed using a validated food frequency questionnaire, and dietary (poly)phenol intake was estimated using the Phenol-Explorer database. Plasma transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) concentrations were measured by ELISA. Logistic regression analyses were performed to evaluate associations between quartiles of (poly)phenol intake and MCI after adjustment for energy intake, age, sex, education, and smoking status.</p><p><strong>Results: </strong>Participants without MCI reported significantly higher intakes of total (poly)phenols and several subclasses, including flavonoids, anthocyanins, flavanones, flavones, hydroxycinnamic acids, and lignans. Higher intakes of flavanones, flavones, lignans, hesperetin, naringenin, lariciresinol, matairesinol, and pinoresinol were positively associated with cognitive performance. Individuals in the highest quartile of total (poly)phenol intake had substantially lower odds of MCI (adjusted OR = 0.08; 95% CI: 0.01-0.62), with similar inverse associations observed for flavonoids (OR = 0.16; 95% CI: 0.02-0.92), lignans (OR = 0.18; 95% CI: 0.04-0.89), flavones (OR = 0.18; 95% CI: 0.04-0.87), naringenin (OR = 0.19; 95% CI: 0.04-0.92), lariciresinol (OR = 0.18; 95% CI: 0.04-0.89), matairesinol (OR = 0.19; 95% CI: 0.04-0.93), and pinoresinol (OR = 0.16; 95% CI: 0.03-0.82), when compared to the lowest quartile. Total (poly)phenol intake was not associated with circulating inflammatory biomarkers, although biochanin A and caffeic acid were inversely associated with TNF-α concentrations.</p><p><strong>Conclusions: </strong>Higher habitual intake of selected dietary (poly)phenols, particularly flavonoids and lignans, was associated with a lower likelihood of MCI and better cognitive performance in older adults. However, the absence of consistent associations with inflammatory biomarkers does not support inference regarding an anti-inflammatory mechanism. Given the observational design, small sample size, and multiple statistical comparisons, these findings should be considered exploratory and hypothesis-generating. Prospective studies and randomized controlled trials are needed to confirm these associations and clarify the underlying biological pathways.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056931","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 : 2026-09-17DOI: 10.3390/antiox15091184
Ana Luísa Rebelo, Luís F Baião, Marta Monteiro, Sofia A Costa Lima
{"title":"Oxidative Stability and Nanoencapsulation of Marine Omega-3 LC-PUFAs for Sustainable Aquaculture and Human Health.","authors":"Ana Luísa Rebelo, Luís F Baião, Marta Monteiro, Sofia A Costa Lima","doi":"10.3390/antiox15091184","DOIUrl":"10.3390/antiox15091184","url":null,"abstract":"<p><p>Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) that make farmed fish valuable to human health, given their bioactivity and highly unsaturated structure that also renders them exceptionally prone to oxidation during feed manufacture and storage, within the fish, and along the supply chain to the consumer. Preserving the oxidative stability, and hence the biological value, of these fatty acids is therefore a central challenge for sustainable aquaculture, made more acute by the replacement of omega-3-rich, oxidatively buffered fish oil with terrestrial oils that lower LC-PUFA content and shift the pro-/antioxidant balance of aquafeeds. Adopting an integrative feed-to-fish-to-consumer perspective, this review examines the strategies proposed to retain and protect EPA and DHA in farmed fish, distinguishing the physiological requirements of fish from the nutritional targets relevant to humans. We first appraise, comparatively, fish oil replacement, finishing diets and nutritional programming, showing that recovery of EPA and DHA is species-, tissue- and context-dependent and seldom complete, with EPA, a key eicosanoid precursor, preferentially catabolised. Through a focused, reproducible literature search, we then evaluate antioxidant-oriented nanoencapsulation as a means of shielding marine LC-PUFAs from oxidation and improving their stability and bioavailability. Although nanoencapsulation consistently enhances oxidative stability and, in the few in vivo studies available, fish performance, the evidence is constrained by heterogeneous and frequently incomplete physicochemical characterisation, scarce storage stability and in vivo data, and largely unaddressed safety, environmental-fate, regulatory, scalability and consumer-acceptance concerns. We conclude that protecting omega-3 oxidative stability will require combining well-characterised delivery systems with species-appropriate nutrition, and we set out the standardised characterisation, required in vivo validation, and integrated safety and life-cycle assessment needed to realise antioxidant-protective, nanotechnology-enabled aquafeeds.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057228","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 : 2026-09-17DOI: 10.3390/antiox15091183
Junying Jiao, Ning Xu, Zhixuan Hong, Lei Chang, Derong Huang, Yang Yu, Zhendi Wang, Yibai Li, Jiaxin Yu, Juntao Guo, You Wang, Lirun Kuang, Yong Wang, Bei Yang, Rui Zhao, Yongyong Hou, Huihui Wang, Qiang Zhang, Ping Xu, Yuanyuan Xu, Jingbo Pi, Jingqi Fu
{"title":"Hepatocyte-Specific <i>Nrf2</i> Deficiency Alters Cholesterol Metabolism, Leading to Mitigated Atherosclerosis in <i>ApoE</i>-Knockout Mice.","authors":"Junying Jiao, Ning Xu, Zhixuan Hong, Lei Chang, Derong Huang, Yang Yu, Zhendi Wang, Yibai Li, Jiaxin Yu, Juntao Guo, You Wang, Lirun Kuang, Yong Wang, Bei Yang, Rui Zhao, Yongyong Hou, Huihui Wang, Qiang Zhang, Ping Xu, Yuanyuan Xu, Jingbo Pi, Jingqi Fu","doi":"10.3390/antiox15091183","DOIUrl":"10.3390/antiox15091183","url":null,"abstract":"<p><p>Hypercholesterolemia and hyperlipidemia are major contributors to the pathogenesis and progression of atherosclerosis and cardiovascular diseases (CVDs). Nuclear factor erythroid-derived 2-like 2 (NRF2) exerts antioxidant and anti-inflammatory effects while regulating glucose and lipid metabolism. However, the precise role and molecular mechanisms of NRF2 in hepatic cholesterol metabolism remain incompletely understood. Approach and Results: <i>ApoE</i>-knockout (<i>ApoE</i>-KO) mice were crossed with hepatocyte-specific <i>Nrf2</i>-knockout (<i>Nrf2</i>(H)-KO) mice to explore how NRF2 modulated cholesterol metabolism and the progression of atherosclerosis in vivo. Atherosclerotic lesion areas in <i>Nrf2</i>(H)-KO;<i>ApoE</i>-KO mice were significantly reduced compared with control counterparts (<i>Nrf2</i>-LoxP;<i>ApoE</i>-KO). Total cholesterol and LDL-cholesterol levels in plasma of <i>Nrf2</i>(H)-KO;<i>ApoE</i>-KO mice were significantly decreased, consistent with atherosclerotic phenotypes. Furthermore, hepatic triglyceride levels and cholesterol contents were increased in <i>Nrf2</i>(H)-KO;<i>ApoE</i>-KO mice. The hepatic transcriptomic analysis highlighted lipid metabolism pathway alterations in <i>Nrf2</i>(H)-KO;<i>ApoE</i>-KO mice, and carboxylesterase 1 (<i>Ces1s</i>) and lipocalin gene family member major urinary proteins (<i>Mups</i>) clusters markedly reduced expression in <i>Nrf2</i>(H)-KO;<i>ApoE</i>-KO livers. Liver proteomics analysis corroborated the transcriptomic findings. The current findings suggest that NRF2-modulated CES1s and MUPs may regulate cholesterol metabolism in the <i>ApoE</i>-KO model. Conclusions: Hepatocyte-specific <i>Nrf2</i> deficiency significantly reduced plasma cholesterol levels, thereby attenuating atherosclerotic plaque formation and progression in the <i>ApoE</i>-KO background. This study established NRF2 in hepatocytes as a potential therapeutic target for controlling hypercholesterolemia and preventing atherosclerosis development.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057187","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":"Melatonin Attenuates Cadmium-Induced Oxidative Stress in Potato by Remodeling Redox Homeostasis and Activating Multi-Pathway Antioxidant Networks.","authors":"Panfeng Yao, Junmei Cui, Wenlin Li, Jianguo Wei, Ying Wang, Chao Sun, Zhenzhen Bi, Zhen Liu, Han Wang, Yuhui Liu, Jiangping Bai","doi":"10.3390/antiox15091180","DOIUrl":"10.3390/antiox15091180","url":null,"abstract":"<p><p>Cadmium pollution severely suppresses potato growth, impairs photosynthesis, and disrupts cellular redox balance, threatening crop yield and food safety. Exogenous small-molecule regulators represent low-cost strategies to alleviate heavy-metal phytotoxicity, yet systematic comparisons of N-acetyl-L-cysteine (NAC), L-tryptophan (Trp), and melatonin (MT) on Cd-stressed potatoes remain insufficient. In this study, two rounds of concentration-gradient screening using morphological and physiological assays identified 5 μM of melatonin as the optimal treatment to alleviate cadmium-induced damage in potato seedlings. This concentration significantly restored shoot height, root length, fresh weight, and chlorophyll content. Relative to the Cd-only control, 5 μM of MT reduced MDA and cadmium accumulation by 51.88% and 49.26%, respectively, while increasing proline content by 40.99%. Transcriptomic analysis revealed that MT reversed Cd-induced suppression of photosynthesis and carbon fixation pathways and activated carbohydrate metabolism. Weighted gene co-expression network analysis identified four key modules significantly correlated with Cd tolerance and MT-mediated recovery. Eight hub genes, including <i>StANNAT1</i> (Ca<sup>2+</sup>-ROS homeostasis), <i>StNRT1.1</i> (nitrogen transport), <i>StSWEET10</i> (carbon allocation), and <i>StHMG1</i> (MVA pathway), were validated by qPCR, confirming their involvement in Ca<sup>2+</sup>-ROS signaling, membrane integrity, and photosynthetic recovery. Mechanistically, MT rebalanced cellular redox status, promoted Cd sequestration, optimized carbon-nitrogen distribution, and enhanced antioxidant defense. These findings demonstrate that exogenous MT alleviates Cd toxicity through coordinated regulation of multiple pathways, providing a practical strategy for safe potato cultivation in Cd-contaminated soils and establishing a molecular framework for understanding MT-mediated heavy-metal tolerance in crops.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057185","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 : 2026-09-17DOI: 10.3390/antiox15091187
Yike Huang, Hujie Lyu, Ren-You Gan
{"title":"Discovery and Characterization of Antioxidant Compounds in the Pericarp and Seed Byproducts of Different Litchi (<i>Litchi chinensis</i> Sonn.) Fruits.","authors":"Yike Huang, Hujie Lyu, Ren-You Gan","doi":"10.3390/antiox15091187","DOIUrl":"10.3390/antiox15091187","url":null,"abstract":"<p><p>The processing of litchi (<i>Litchi chinensis</i> Sonn.) fruits generates substantial amounts of pericarp and seed by-products, which are candidate sources of antioxidant compounds but are underutilized. This study systematically investigated the total phenolic content (TPC) and in vitro antioxidant capacities (FRAP, ABTS, and DPPH values) of pericarp and seed extracts across eight commercial litchi cultivars. Qualitative LC-MS-based phytochemical profiling was further performed on the representative 'Bingli' cultivar. The results indicated that litchi seeds consistently exhibited significantly higher TPC and antioxidant activities compared to pericarps. Among the tested pericarps, the 'Nuomici' cultivar showed the highest TPC (10.29 ± 0.10 mg GAE/g dw) and antioxidant capacities. The 'Bingli' cultivar demonstrated the highest overall antioxidant activity among seeds (e.g., TPC of 33.92 ± 1.75 mg GAE/g dw and FRAP of 373.06 ± 4.64 μmol Fe(II)/g dw). LC-MS-based qualitative screening tentatively annotated several hydroxycinnamic acids and A-type procyanidins as putative phenolic constituents of the 'Bingli' litchi pericarp and seed extracts. Subsequent targeted HPLC analysis determined the concentrations of Procyanidin A2, revealing that it had a high concentration in the 'Xianjinfeng' and 'Bingli' seeds (1298.73 ± 54.87 and 1127.81 ± 67.22 μg/g dw, respectively). These findings indicate cultivar- and tissue-specific variations in litchi fruit by-products and suggest that the seeds of 'Bingli' and 'Xianjinfeng' are candidate sources of antioxidant phenolics for further investigation, pending validation in food models or biological systems.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057014","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 : 2026-09-17DOI: 10.3390/antiox15091179
Rahul S Patil, Shweta R Patil, Joyce N Gonzales, Alexander D Verin
{"title":"Emerging Role, Molecular Mechanisms, and Therapeutic Potential of 2-O, 3-O Desulfated Heparin (ODSH) Across Inflammatory and Vascular Diseases.","authors":"Rahul S Patil, Shweta R Patil, Joyce N Gonzales, Alexander D Verin","doi":"10.3390/antiox15091179","DOIUrl":"10.3390/antiox15091179","url":null,"abstract":"<p><p>Glycosaminoglycans (GAGs) are structurally diverse polysaccharides that regulate inflammation, coagulation, and cellular homeostasis through highly specific sulfation patterns and interactions with cationic proteins. Among GAG derivatives, 2-O, 3-O desulfated heparin (ODSH) is a chemically modified heparin derivative characterized by markedly reduced anticoagulant activity yet preserved affinity for key inflammatory mediators. This review summarizes current knowledge on ODSH structure-function relationships, molecular mechanisms, and therapeutic applications across inflammatory, vascular, and immune-mediated diseases. ODSH modulates several convergent pathogenic processes, including HMGB1-RAGE/TLR4 signaling, neutrophil elastase-mediated tissue injury, PF4-dependent platelet activation, selectin-mediated adhesion, and thrombin-induced endothelial permeability. These actions arise from both direct molecular interactions and indirect sequestration of extracellular mediators, collectively associated with reduced cytokine release, enhanced endothelial barrier stability, and attenuation of inflammation-coagulation crosstalk. Preclinical studies report protective effects in acute lung injury, cystic fibrosis, ischemia-reperfusion injury, traumatic brain injury, thrombocytopenia, and metastatic cancer. Some pilot clinical observations in acute myeloid leukemia and septic peritonitis have reported favorable biological effects. Despite multimodal activity, limitations include incomplete pharmacokinetic characterization, limited comparative studies with other desulfated heparins, and the need for dose-response and safety evaluation in human trials. Overall, available evidence suggests that ODSH may have therapeutic relevance in diseases characterized by excessive inflammation, endothelial dysfunction, and dysregulated host responses. This review integrates current evidence to guide future mechanistic and translational investigation into ODSH and related low-anticoagulant heparin derivatives.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056994","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 : 2026-09-17DOI: 10.3390/antiox15091185
Suhyeon Lee, Yumin Sim, Minkyeong Lee, Eunju Kim
{"title":"Hesperetin Attenuates Experimentally Induced Skeletal Muscle Dysfunction by Modulating Time-of-Day-Dependent Gene Expression and Mitochondrial Redox-Related Markers.","authors":"Suhyeon Lee, Yumin Sim, Minkyeong Lee, Eunju Kim","doi":"10.3390/antiox15091185","DOIUrl":"10.3390/antiox15091185","url":null,"abstract":"<p><p>Skeletal muscle aging is characterized by impaired myogenic differentiation, mitochondrial dysfunction, oxidative stress, and circadian rhythm disruption, contributing to sarcopenia and muscle atrophy. Hesperetin, a natural flavonoid, has antioxidant and mitochondrial protective effects; however, its role in skeletal muscle circadian regulation during aging remains unclear. This study investigated the effects of hesperetin (20 µM or 100 mg/kg b.w.) using D-galactose (D-gal, 20 g/L)-induced senescent C2C12 myotubes, a D-gal (150 mg/kg b.w., i.p.)-induced aging mouse model, and a dexamethasone (Dex, 20 mg/kg b.w., i.p.)-induced muscle atrophy model. In D-gal-treated mice, hesperetin improved hanging test performance and increased SDH-positive area, particularly during the active phase. Hesperetin also partially modulated core clock gene expression and mitochondrial function-related gene expression. In D-gal-induced senescent C2C12 myotubes, hesperetin improved myotube formation, reduced SA-β-gal-positive cells, DCF-DA fluorescence, and MDA levels, enhanced antioxidant enzyme activities, and improved mitochondrial-associated functional indicators, including ATP levels, mitochondrial membrane potential-related fluorescence, <i>pMitoTimer</i>-based mitochondrial oxidation-associated signals, and <i>Ppargc1a</i> expression patterns. These findings suggest that hesperetin may protect against experimentally induced skeletal muscle dysfunction by modulating time-dependent gene expression, mitochondrial-related activities, and muscle-related functional markers.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057212","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 : 2026-09-17DOI: 10.3390/antiox15091186
Cristian Ioan Iuhas, Andreea Stănilă, Carmen Socaciu, Vlad N Dudric, Corina Danciu, Melania Florina Munteanu, Răzvan Ciortea, Cristina Mihaela Ormindean, Andrei Măluțan, Zorița Diaconeasa, Dan Mihu, Liora Colobatiu
{"title":"Polyphenols as Modulators of Oxidative Stress and Inflammation in Endometriosis: Molecular Mechanisms and Clinical Perspectives.","authors":"Cristian Ioan Iuhas, Andreea Stănilă, Carmen Socaciu, Vlad N Dudric, Corina Danciu, Melania Florina Munteanu, Răzvan Ciortea, Cristina Mihaela Ormindean, Andrei Măluțan, Zorița Diaconeasa, Dan Mihu, Liora Colobatiu","doi":"10.3390/antiox15091186","DOIUrl":"10.3390/antiox15091186","url":null,"abstract":"<p><p>Endometriosis, a chronic inflammatory condition affecting up to 10% of reproductive-age individuals, is characterized by the presence of endometrial-like tissue outside the uterine cavity. Current treatments are based primarily on hormonal therapy, analgesia, and surgery, while additional biologically targeted approaches remain under investigation. This review examines polyphenols in relation to endometriosis-associated redox dysregulation and inflammation. Rather than acting simply as antioxidants, individual polyphenols may function as context-dependent redox and signaling modulators. Preclinical studies suggest effects on NF-κB and MAPK signaling, Nrf2-related stress responses, angiogenesis, apoptosis, immune-cell activity, and hormone-related pathways, but the direction and magnitude of these effects differ substantially among compounds, doses, metabolites, and experimental models. Resveratrol and quercetin have generated the greatest clinical interest; however, human evidence remains sparse and heterogeneous, quercetin has been evaluated mainly in multicomponent formulations, and the only double-blind placebo-controlled randomized trial of resveratrol did not demonstrate superiority over placebo for pain reduction. Low and variable bioavailability, compound-specific metabolism, phytoestrogenic and pro-oxidant effects at some exposures, heterogeneous formulations, and limited long-term safety data remain major translational barriers. Polyphenols should therefore be regarded as potential adjunctive approaches whose clinical efficacy in endometriosis remains to be established.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057238","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}