Antioxidants最新文献

{"title":"Mitochondrial DNA Haplogroups Influence Oxidative Stress Profiles and Susceptibility to Metabolic Syndrome in an Asian Population.","authors":"Shao-Wen Weng, Yu-Han Lin, Shih-Hsuan Chen, Tsu-Kung Lin, Pei-Wen Wang, Chia-Wei Liou","doi":"10.3390/antiox15091155","DOIUrl":"10.3390/antiox15091155","url":null,"abstract":"<p><p>Mitochondrial DNA (mtDNA) haplogroups influence mitochondrial function and reactive oxygen species (ROS) production, potentially modulating susceptibility to metabolic disorders. This study investigated the associations between mtDNA haplogroups, systemic oxidative stress, and metabolic syndrome in 2486 Taiwanese individuals. Serum thiobarbituric acid-reactive substances (TBARS) and free thiols were measured as markers of oxidative and antioxidative status, respectively, while mtDNA haplogroups were determined using multiplex PCR and Luminex genotyping. Macrohaplogroups N (51%) and M (49%) were predominant, with haplogroups B, F, D, and M7 most frequently observed. Although the overall haplogroup distribution is genetically similar to populations in Southern China, the distribution among the Taiwanese population shows distinct differences. Haplogroup B was significantly associated with higher TBARS levels, lower thiol concentrations, and an increased prevalence of diabetes and metabolic syndrome (OR 1.34, <i>p</i> = 0.004). Individuals with metabolic syndrome exhibited higher oxidative stress and lower antioxidative biomarker levels than those without the syndrome, while a progressive imbalance in oxidative-antioxidative status was observed with increasing numbers of metabolic syndrome components. These findings suggest that mtDNA haplogroups, particularly haplogroup B, may contribute to metabolic syndrome susceptibility through modulation of systemic oxidative stress.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057191","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":"Macrophage Immune-Redox Modulation by Phenylethanoid- and Flavonoid-Rich Botanical Extracts: NF-κB/iNOS-Nrf2 Crosstalk and the Proposed Role of <i>Buddleja globosa</i>.","authors":"Yilka Mena-Linares, Humberto Vélez-Slimani, Luis A Salazar","doi":"10.3390/antiox15091158","DOIUrl":"10.3390/antiox15091158","url":null,"abstract":"<p><p>Macrophage activation depends on the balance between pro-inflammatory signaling and cytoprotective antioxidant responses. Persistent nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) activity, together with insufficient nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, promotes oxidative and nitrosative stress and contributes to chronic inflammation. Phenylethanoid- and flavonoid-rich botanical extracts may modulate this immune-redox network, but the available evidence is dispersed across plant species, extraction procedures, isolated compounds, and experimental models. This review examines the phytochemical composition and biological effects of these preparations, with particular emphasis on <i>Buddleja globosa</i> Hope. Evidence concerning verbascoside, luteolin, apigenin, quercetin derivatives, and other constituents is integrated with findings related to toll-like receptor 4/NF-κB signaling, iNOS-derived nitric oxide, inflammatory cytokines, reactive oxygen species, and Keap1-Nrf2-dependent cytoprotective responses. Direct evidence obtained with <i>B. globosa</i> extracts is distinguished from mechanistic findings generated using isolated constituents or related botanical preparations. Current studies support antioxidant and inflammation-modulating activities, but interpretation is limited by phytochemical variability, inconsistent dosing, incomplete cytotoxicity assessment, and limited use of macrophage-specific models. Future work should prioritize chemically standardized extracts, direct extract-constituent comparisons, pathway-specific validation, and formulation strategies that improve stability, reproducibility, and biological performance.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057226","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":"Plasma-Derived Extracellular Vesicles as Systemic Mediators of Radiation Response and Radiation Mitigation by Activated Protein C in a Rat Model.","authors":"Shivani Bansal, Sunain Deol, Meth Jayatilake, Yaoxiang Li, Brian L Fish, Xiao Xu, Jose A Fernandez, John H Griffin, Tracy Gasperetti, Meetha Medhora, Marjan Boerma, Heather A Himburg, Amrita K Cheema","doi":"10.3390/antiox15091160","DOIUrl":"10.3390/antiox15091160","url":null,"abstract":"<p><p>Radiological emergencies necessitate biomarkers that not only estimate absorbed ionizing radiation (IR) dose but also guide timely interventions to prevent or delay multi-organ injury. Conventional LC-MS-based metabolomics of bulk plasma is constrained by matrix effects that mask low-abundance species. Extracellular vesicles (EVs) constitute a metabolically enriched, underexplored compartment that can provide complementary insight into systemic metabolic and redox responses to IR. Female WAG/RijCmcr rats were exposed to 13.0 Gy leg-out partial-body X-rays and treated with one of three activated protein C (APC) variants-rat wild-type (WT), rat 3K3A-APC, or human WT APC-administered 24- and 48 h post-irradiation. Longitudinal plasma collections (days 1, 14, 30, and 90) were subjected to metabolomic and lipidomic profiling of whole plasma and matched EV-enriched fractions to define signatures of acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and their modulation by APC. ARS was marked by early dyslipidemia and widespread metabolic disruption, evolving into DEARE with persistent alterations in energy metabolism, and nucleotide biosynthesis, consistent with sustained oxidative and inflammatory stress. EV profiles showed matrix-specific, time-dependent trajectories distinct from plasma, with prominent lipid dysregulation and enrichment of fatty acid β-oxidation, sphingolipid, and cholesterol pathway metabolites at day 90. Rat 3K3A-APC promoted early EV metabolic normalization, whereas rat WT APC more effectively mitigated late DEARE-associated changes. Elevated sphingomyelins in plasma EVs at day 90 may suggest a compensatory or anti-inflammatory lipid response. These findings suggest that plasma-derived EVs may provide a sensitive matrix for radiation biomarker discovery and may help elucidate APC-mediated modulation of IR-induced metabolic and redox disturbances.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057202","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":"Ultrasound-Assisted Recovery and Biological Evaluation of an Astaxanthin-Containing Extract from <i>Chara corallina</i>.","authors":"Natthrit Roekngam, Wanninee Chankaew, Suwichak Chaisit, Sonsawan Kongpuckdee, Sunisa Khongthong","doi":"10.3390/antiox15091159","DOIUrl":"10.3390/antiox15091159","url":null,"abstract":"<p><p>Oxidative stress and chronic inflammation are major contributors to skin photoaging, highlighting the need for natural antioxidants with multifunctional bioactivities. This study developed an ultrasound-assisted extraction (UAE) strategy to recover an astaxanthin-rich extract from the underutilized freshwater macroalga <i>Chara corallina</i> and evaluated its antioxidant, anti-inflammatory, and anti-photoaging properties. Different solvent systems were evaluated for extraction efficiency, and astaxanthin-equivalent recovery was quantified by high-performance liquid chromatography with photodiode array detection (HPLC-PDA). Antioxidant activity was evaluated using the DPPH radical scavenging assay, whereas biological activities were assessed in human dermal fibroblasts and RAW264.7 macrophages using cell viability assays, quantitative real-time PCR, and extracellular matrix-related enzyme inhibition assays. The selected solvent system (48% ethanol in ethyl acetate) provided the highest astaxanthin-equivalent recovery (0.2598 ± 0.0086% <i>w</i>/<i>w</i>). The selected CCE exhibited DPPH radical-scavenging activity, modulated antioxidant- and inflammation-associated gene expression, increased <i>COL1A2</i> mRNA expression, and inhibited collagenase, elastase, and hyaluronidase within the evaluated concentration range. HPLC-PDA analysis revealed a chromatographic component with retention-time and UV-visible spectral characteristics corresponding to those of an authentic astaxanthin reference standard; however, comprehensive structural and phytochemical characterization was not performed. Because CCE is a chemically complex extract, the observed biological responses cannot be attributed exclusively to astaxanthin. Overall, these findings provide an initial basis for further investigation of <i>C. corallina</i> as an underexplored freshwater source of carotenoid-containing bioactive extracts rather than establishing it as a commercially competitive source of natural astaxanthin.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057352","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":"Fungal-Derived Decahydrofluorene Alkaloids Promote Mitochondrial Resilience and Neuroprotection in Cellular and Animal Models of Parkinson's Disease.","authors":"Alberto Vázquez-Jiménez, Margarita M Marques, José M Sánchez, Jesús Agulla, Rebeca Lapresa, Mónica Trigal-Martínez, Rosalía Fernández-Alonso, Gracia Merino, Antonio Fernández, Antonella Consiglio, Juan P Bolaños, Ángeles Almeida, María C Marín, Lorena López-Ferreras","doi":"10.3390/antiox15091151","DOIUrl":"10.3390/antiox15091151","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by oxidative stress, mitochondrial dysfunction, and dopaminergic neuron loss, for which effective treatments remain unavailable. Here, we report CL0179, a fungal-derived decahydrofluorene alkaloid with antioxidant-associated neuroprotective properties, and evaluate its effects across cellular and animal PD models. CL0179 exhibited a favorable safety profile and protected SHSY5Y against 6-hydroxydopamine- (6-OHDA), rotenone-, and 1-Methyl-4-phenylpyridinium-iodide (MPP⁺)-induced neurotoxicity by preserving mitochondrial membrane potential and network integrity. Transcriptomic analyses revealed selective restoration of gene-expression programs associated with oxidative phosphorylation, mitochondrial bioenergetics, and stress adaptation disrupted by MPP⁺. CL0179 also enhanced SIRT1 activity under MPP⁺ stress, whereas pharmacological SIRT1 inhibition partially attenuated protection of mitochondrial membrane potential and cell viability. In <i>LRRK2</i>-G2019S astrocytes, CL0179 reduced ROS and α-synuclein accumulation and restored mitochondrial organization, while in human dopaminergic neurons, it attenuated toxin-induced mitochondrial depolarization and preserved neuronal architecture. To overcome the low production of CL0179, we generated the structurally related analogue CL0670. Both compounds crossed the blood-brain barrier and protected mouse primary cortical neurons, while CL0670 improved motor deficits in a 6-OHDA mouse model. Collectively, these compounds promote mitochondrial resilience and stress-adaptive neuroprotection, supporting their potential for PD and related neurodegenerative disorders.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057162","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":"Urinary Extracellular Vesicle-Derived miRNAs Reveal a Coordinated Stress-Response Network Linked to Advanced Glycation End-Products in Children and Adolescents.","authors":"Fabio Lauria, Paola Russo, Alfonso Siani, Ivana Sirangelo, Ilenia D'Orsi, Pasquale Marena, Antje Hebestreit, Ronja Foraita, Giuseppe Iacomino","doi":"10.3390/antiox15091150","DOIUrl":"10.3390/antiox15091150","url":null,"abstract":"<p><p>The widespread consumption of ultra-processed foods increases exposure to advanced glycation end-products (AGEs), key mediators of oxidative stress and chronic low-grade inflammation. Although AGEs contribute to adult metabolic dysfunction, their early molecular correlates in pediatric populations remain insufficiently defined. Extracellular vesicle (EV)-associated miRNAs represent stable, non-invasive indicators of systemic stress responses. This study evaluated the association between urinary AGEs and urinary EV-associated miRNAs in 94 Italian children and adolescents from the I.Family cohort. Fluorescent AGEs were quantified via spectrofluorimetry, and EV-enriched urinary miRNAs were profiled using next-generation sequencing. Differential expression and multivariable generalised linear models (adjusted for age, sex, BMI z-score, and hs-CRP) were performed. Differential expression analysis revealed a significant upregulation of hsa-miR-4516 in participants with high versus low urinary AGE levels (fold change = 2.31; FDR = 0.024). In multivariable continuous models, hsa-miR-4516 remained the primary AGE-associated miRNA, though the association attenuated following adjustment for BMI z-score and hs-CRP. Functional enrichment and network analyses highlighted pathways governing oxidative stress responses, proteostasis, and cellular survival. Overall, urinary EV-associated miRNAs may reflect coordinated biological responses to dietary AGE burden rather than serving as direct exposure biomarkers, offering integrated, non-invasive insights into early metabolic and inflammatory adaptations in children.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057316","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":"CYP2D6 as an Emerging Endogenous Oxidative Stress Modulator in Cardiovascular Disease: Genetic, Pharmacological, and Redox Perspectives.","authors":"Cheng-Wu Yang, Wen-Hua Chen, Tzong-Shyuan Lee","doi":"10.3390/antiox15091154","DOIUrl":"10.3390/antiox15091154","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Oxidative stress is a central and well-established driver of cardiovascular disease, contributing to mitochondrial dysfunction, endothelial injury, inflammatory activation, and progressive myocardial and vascular remodeling. Although the major endogenous sources of cardiovascular reactive oxygen species (ROS), including NADPH oxidases, mitochondrial electron transport chain leakage, and uncoupled nitric oxide synthase, are well characterized, an additional and underappreciated contributor has recently emerged: cytochrome P450 2D6 (CYP2D6), an enzyme classically regarded as a hepatic drug-metabolizing protein. Accumulating evidence indicates that CYP2D6 is expressed extrahepatically in cardiac, vascular, and neural tissue, where uncoupled catalytic cycling is proposed to generate ROS independently of its canonical xenobiotic-metabolizing role, although direct experimental evidence for this pathway in human cardiac and vascular tissue remains limited. CYP2D6-derived oxidative processes may interact with mitochondrial respiratory function, endothelial nitric oxide bioavailability, and redox-sensitive inflammatory pathways, potentially contributing to cardiovascular vulnerability under specific genetic or pathological conditions. Critically, the magnitude of this oxidative contribution is not fixed: it is dynamically shaped by inherited CYP2D6 genetic variation, with poor and ultra-rapid metabolizer phenotypes exhibiting divergent oxidative burden and pharmacokinetic vulnerability, and is further amplified by polypharmacy, multimorbidity, and inflammation-driven phenoconversion, whereby clinically expressed CYP2D6 activity diverges from inherited genotype in ways that intensify redox imbalance. These dynamics are particularly relevant in East Asian populations, where the decreased-function CYP2D6*10 allele is highly prevalent. In this narrative, hypothesis-generating review, we integrate evidence from pharmacogenomics, redox biology, and cardiovascular pharmacology to propose a conceptual framework that reframes CYP2D6 as a genetically and pharmacologically tunable node within cardiovascular redox biology. We further examine emerging redox biomarkers, multi-omics platforms, and AI-assisted modeling as translational strategies for capturing this dynamic oxidative risk in real time. This framework supports a shift from static genotype-guided prescribing toward oxidative-risk-informed, adaptive cardiovascular precision medicine. Importantly, our focus on CYP2D6 should not be interpreted as evidence that it is a major cardiovascular CYP isozyme or an established driver of cardiovascular pathology. Rather, CYP2D6 is examined here as a deliberately hypothesis-generating candidate whose unusually strong pharmacogenetic variability, clinically important cardiovascular drug substrates, dynamic susceptibility to phenoconversion, extrahepatic expression, and mechanistically plausible links to endogenous substrate metabolism and CYP-associated ROS generati","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056937","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":"Cunermuspir, a Copper(I)-Niacin Complex, Modulates Mitochondrial Respiration and Cellular Oxidant Handling in Fibroblasts from Children with Autism Spectrum Disorder.","authors":"Sophie Wallace, Spencer Lawes, Adrienne C Scheck, Richard E Frye","doi":"10.3390/antiox15091147","DOIUrl":"10.3390/antiox15091147","url":null,"abstract":"<p><p>Copper is a redox-active transition metal that is essential for the assembly and catalytic function of cytochrome c oxidase (Complex IV), the terminal enzyme of the mitochondrial electron transport chain and a principal site of physiological oxygen reduction. Elevated Complex IV activity and respiratory chain uncoupling are among the most consistently replicated biological findings in autism spectrum disorder (ASD), yet the interaction between mitochondrial copper delivery, respiration, and cellular oxidant handling in ASD has not been systematically defined. We treated dermal fibroblasts from 9 children with ASD and 10 typically developing controls with the copper(I)-niacin complex Cunermuspir (0, 50, or 100 µM for 1 or 24 h exposure) and challenged them with graded concentrations (0-5.0 µM) of the redox-cycling agent 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). Mitochondrial respiration was profiled by Seahorse XF respirometry (2133 observations across 28 experiments), and cellular reactive oxygen species (CellROX™ Green) and mitochondrial mass/polarization (MitoTracker™ Deep Red) were quantified by fluorescence imaging. ASD fibroblasts displayed a hypermetabolic, uncoupled respiratory phenotype (~73% higher baseline respiration; ~109% higher proton leak; reduced coupling efficiency). Linear mixed models with polynomial dose terms revealed significant ASD × Cunermuspir complex interactions (ASD × Cunermuspir and/or their higher-order interactions with DMNQ and treatment) for four respiratory parameters. ASD cells exhibited lower steady-state oxidation-dependent CellROX™ Green fluorescence than controls despite greater respiratory uncoupling, as well as lower steady-state MitoTracker™ Deep Red fluorescence; Cunermuspir reshaped the MitoTracker™ DMNQ dose-response in an ASD-selective manner. These findings identify the Cunermuspir-associated modulation of the ASD mitochondrial and oxidant handling phenotype and motivate further mechanistic and translational evaluation.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056871","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":"Oxidative Stress in Vascular Aging: Therapeutic Potential of the Antioxidant Paradox. A State-of-the-Art Review.","authors":"Aleyma Veliz Perez, Mihaela Badea, Sehrish Bilal","doi":"10.3390/antiox15091152","DOIUrl":"10.3390/antiox15091152","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with aging as one of its main risk factors. Cellular senescence and oxidative stress form a bidirectional vicious cycle that drives vascular aging, endothelial dysfunction, and atherosclerotic progression. This state-of-the-art review synthesizes current evidence on the interplay between oxidative stress and senescence in cardiovascular aging and critically assesses whether antioxidant strategies can benefit vascular health. A targeted literature search was conducted in PubMed/MEDLINE, Web of Science, and Scopus (2016-2026). While endogenous antioxidant defenses decline with age, exogenous antioxidants, including resveratrol, vitamins C and E, omega-3 fatty acids, carotenoids, and coenzyme Q10,demonstrate promising preclinical effects, yet large-scale clinical trials have yielded inconsistent results. The VITAL and STRENGTH trials failed to demonstrate significant cardiovascular benefit with omega-3 supplementation, and elevated serum β-carotene was found paradoxically associated with increased cardiovascular mortality. Emerging mitochondria-targeted antioxidants (MitoQ, MitoTEMPO) show preclinical promise but require further clinical validation. Current evidence does not support antioxidant supplementation for cardiovascular prevention. Lifestyle interventions, particularly antioxidant-rich dietary patterns such as the Mediterranean diet, remain the safest strategy. Future research should develop personalized approaches guided by oxidative stress biomarkers and long-term trials.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057247","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":"Valorization of Sardinian Grapevine Leaves as a Sustainable Source of Flavonols with Anticancer Potential.","authors":"Ylenia Spissu, Maria Lauda Tomasi, Carla Cossu, Andrea Floris, Emanuela Azara, Gavina Rita Serra, Irene Marchesi, Francesco Paolo Fiorentino, Gaia Rocchitta, Riccarda Zappino, Antonio Barberis","doi":"10.3390/antiox15091153","DOIUrl":"10.3390/antiox15091153","url":null,"abstract":"<p><p>Grapevine (<i>Vitis vinifera</i> L.) leaves are an abundant agricultural by-product and an underexploited source of bioactive polyphenols. This study characterized hydroalcoholic leaf extracts from autochthonous Sardinian cultivars and evaluated their effects in RKO human colorectal carcinoma cells. LC-HRMS revealed flavonol-rich profiles dominated by glycosylated derivatives of quercetin, kaempferol, and isorhamnetin, with marked cultivar-dependent differences and higher total flavonol abundance in Cannonau and Nieddera. Cyclic voltammetry showed distinct redox reactivity among extracts, with Vermentino and Martellada Bianca displaying the strongest electrochemical responses, consistent with their modulation of intracellular reactive oxygen species. In RKO cells, the extracts reduced metabolic activity in a dose-dependent manner, with IC50 values ranging from 100.3 to 251.8 µg/mL. At the molecular level, treatments modulated c-myb expression and shifted the bax/bcl2 balance toward a pro-apoptotic profile. These effects were supported by DAPI staining, showing chromatin condensation and nuclear fragmentation, and by moderate activation of caspase-3/7. Overall, Sardinian grapevine leaf extracts showed cultivar-specific phenolic composition, redox activity, and pro-apoptotic effects in an in vitro colorectal cancer model, supporting their potential valorization as sustainable sources of bioactive compounds. Further studies addressing bioavailability, metabolism, and in vivo effects are required to assess their physiological relevance and translational potential.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057300","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}