搜索结果：Antioxidants & redox signaling

Exercise-induced reactive oxygen and nitrogen species (RONS) serve as crucial signaling molecules for training adaptation, mitochondrial biogenesis, and inflammatory resolution, rather than being mere markers of oxidative damage. Chronic or excessive high-dose antioxidant supplementation may suppress these vital redox-sensitive pathways. Consequently, this narrative review examines food-based antioxidant strategies as approaches for redox modulation, meaning support for recovery and redox homeostasis without indiscriminately suppressing exercise-induced redox signals that may contribute to training adaptation, while emphasizing the distinction between whole-food matrices and isolated supplements. A structured literature search was conducted across major electronic databases, including PubMed, Web of Science, Scopus, and SPORTDiscus. The search focused on intersecting themes of exercise physiology, redox biology, and sports nutrition. The reviewed evidence includes short-term human intervention studies, systematic reviews, meta-analyses, and mechanistic studies examining tart cherry, berries, pomegranate, cocoa, green tea, beetroot, extra virgin olive oil, and Mediterranean-style dietary patterns. Overall, the evidence suggests that these food-based strategies may influence recovery-related outcomes through mechanisms extending beyond direct radical scavenging, including inflammatory regulation, vascular function, and gut-derived metabolism; however, the strength and consistency of findings vary by food source, outcome, dose, timing, study population, dietary matrix, and bioavailability. Current literature does not support universal, fixed daily antioxidant use. Food-based strategies appear most appropriate during periods of elevated recovery demands, such as heavy training blocks, congested competition, muscle damage, or environmental stress. Food-based antioxidant nutrition should therefore be interpreted as a conceptual, evidence-informed approach to periodized and context-specific recovery support, rather than as a universal or evidence-graded guideline, because much of the available evidence derives from short-term and heterogeneous intervention studies. These strategies should complement foundational sports nutrition practices (energy availability, macronutrient distribution, hydration, and sleep) when balancing the preservation of long-term training adaptations with the need for acute recovery.

Ischemic stroke induces oxidative stress, neuroinflammation, neuronal death, and synaptic dysfunction, leading to persistent motor and cognitive deficits. The human dental pulp stem cell (hDPSC) secretome is a promising cell-free therapeutic candidate containing neurotrophic, antioxidant, and immunomodulatory factors. Here, we investigated its therapeutic effects in a photothrombotic mouse model of ischemic stroke and CoCl2-induced hypoxic BV2 microglial cells. Proteomic profiling identified antioxidant-associated proteins, including SOD2, GSR, and GSTP1, and microglial phenotype-related candidates, including GRN, CSF1, and LRP1. hDPSC secretome treatment reduced stroke-induced infarct volume and attenuated stroke-increased neuronal apoptosis, neuronal ROS accumulation, and NF-κB-associated inflammatory signaling in the cortex and hippocampus. It also shifted microglial marker expression toward an M2-associated profile and improved stroke-impaired hippocampal neurogenesis, vascular remodeling, and synaptic organization. Proteomic analyses further identified coordinated changes in pathways related to oxidative phosphorylation, inflammatory responses, calcium signaling, SNARE-associated vesicular transport, and ROBO-Rho-associated cytoskeletal remodeling. These molecular and cellular changes were associated with improved motor coordination, spatial learning and memory, contextual memory, and anxiety-like behavior. These findings support the hDPSC secretome as a cell-free therapeutic candidate for post-stroke functional recovery linked to redox, inflammatory, neurovascular, and synaptic remodeling.

Background: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition associated with high morbidity and mortality, characterized by severe inflammation, oxidative stress, impaired gas exchange, and progressive lung injury. Disruption of cellular redox homeostasis plays a central role in ARDS pathogenesis, making redox-regulatory mechanisms attractive therapeutic targets. Methods: This review evaluates experimental evidence on protein-mediated regulation of oxidative stress pathways in ARDS, focusing on proteins involved in antioxidant defense, reactive oxygen species (ROS) generation, mitochondrial signaling, and maintenance of cellular redox homeostasis. Results: Current evidence indicates that key regulatory proteins modulate oxidative stress by activating endogenous antioxidant defense systems, regulating ROS production, and influencing mitochondrial signaling pathways. These mechanisms reduce oxidative damage and pulmonary inflammation while preserving cellular redox balance. Experimental studies further demonstrate that modulation of specific protein regulators enhances cellular resilience under hypoxic and inflammatory conditions characteristic of ARDS. Conclusions: Protein-mediated regulation of redox signaling represents a promising therapeutic strategy for ARDS. Targeting redox-regulatory proteins may attenuate oxidative stress, reduce lung inflammation, and improve cellular survival, supporting their potential as novel therapeutic targets. Further preclinical and clinical studies are needed to validate these findings and facilitate their translation into clinical practice.

Nitric oxide (NO) improves postharvest jujube resistance, yet the specific molecular targets remain elusive. Here, we identify the endoplasmic reticulum chaperone ZjPDI1 as a functional target of NO-mediated immunity. Exogenous NO restricted lesion expansion by inducing the expression of ZjPDI1, antioxidant, and defense-related genes. Biochemical assays confirmed that ZjPDI1 is specifically S-nitrosylated at Cys123 and Cys126 within its CGHC catalytic motif. Molecular dynamics simulations demonstrated that this modification increases the structural flexibility of ZjPDI1. In vivo transient overexpression of ZjPDI1 enhanced disease resistance, resulting in H2O2 accumulation and the transcriptional activation of downstream defense genes. Yeast two-hybrid and pull-down assays confirmed a physical interaction between ZjPDI1 and ZjERO1, coupling the ER protein folding complex to the defense-associated redox signaling. These findings indicate that S-nitrosylation alters the conformation of ZjPDI1, and its interaction with ZjERO1 likely serves as a mechanistic basis for the H2O2 accumulation to activate postharvest disease resistance.

Oxidative stress has been recognized as a repeatedly validated pathophysiological factor in schizophrenia, but its mechanistic role and translational relevance remain incompletely defined. Prior work has advanced redox dysregulation, neuroinflammation, and NMDA receptor hypofunction as a putative central hub in schizophrenia. This narrative review proposes an evidence-weighted redox-mitochondria-immune framework that integrates peripheral biomarkers, magnetic resonance spectroscopy, postmortem findings, and preclinical mechanisms while explicitly distinguishing established observations from candidate pathways. Existing studies support increased oxidative damage and altered antioxidant buffering in schizophrenia, particularly involving the glutathione system. However, these abnormalities are neither uniform across disease stages nor equally represented across patient subgroups, and may be markedly prominent only in certain biological subgroups. Mechanistically, redox imbalance may interact with mitochondrial bioenergetic deficits and innate immune signaling; however, pathway-specific links such as cGAS-STING activation, nitrosative/peroxynitrite stress, and GPx4-ferroptosis should currently be treated as testable extensions rather than validated human mechanisms in schizophrenia. Importantly, the pathological consequences of oxidative stress are unlikely to be cell-type neutral. Parvalbumin-positive interneurons and oligodendrocyte lineage cells are more vulnerable because of their high metabolic load, limited antioxidant buffering capacity, and lipid/iron-related susceptibility, thereby providing a mechanistic bridge to excitation-inhibition imbalance, myelin abnormalities, and reduced circuit synchrony. Microglial redox-inflammatory signaling may further exacerbate these processes. On the basis of this framework, we argue that the key for future research is not to continue demonstrating the universality of oxidative stress, but to improve the translational efficiency. Biomarker-guided stratification, stage-sensitive study designs, and cell-type-informed therapeutic strategies may therefore provide a more productive path toward redox-targeted interventions in schizophrenia.

Aluminum toxicity severely limits crop productivity by disrupting nutrient balance, photosynthesis, and cellular redox homeostasis. Gamma aminobutyric acid (GABA) is an important signaling molecule involved in plant stress adaptation, but its role in regulating sulfur metabolism and antioxidant defense under aluminum stress remains poorly understood. This study investigated the impact of foliar application of GABA (100 μmol L-1) on aluminum tolerance in Camelina sativa exposed to Al stress (50 mg kg-1 soil Al) using controlled experiments and naturally aluminum-contaminated mining soil. GABA application significantly improved plant performance by increasing plant height, biomass, root growth, photosynthetic pigments, and gas exchange parameters compared with Al-stressed plants. In addition, GABA enhanced antioxidant protection by increasing the activities of ascorbate peroxidase, catalase, peroxidase, and superoxide dismutase, while reducing reactive oxygen species accumulation and the malondialdehyde content by improving the redox balance. GABA treatment increased glutathione levels and the GSH/GSSG ratio, whereas the accumulation of oxidized glutathione and dehydroascorbic acid induced by aluminum stress decreased, indicating improved antioxidant recycling capacity. Furthermore, GABA restored sulfur metabolism by regulating cysteine, glucosinolate, glutathione S-transferase activity, and the expression of sulfur-related genes, including ST5a b c, CYP83A1, and BCAT4. Functional inhibitor experiments demonstrated that the protective role of GABA depends on calcium signaling and reactive oxygen species signaling pathways. Transcriptome analysis further revealed extensive regulation of genes involved in antioxidant defense and sulfur metabolism. These findings demonstrate that GABA enhances aluminum tolerance through coordinated regulation of sulfur metabolism, redox homeostasis, and stress signaling, providing new insights into sustainable strategies for improving crop resilience in aluminum-affected soils.

Yemen has long employed the ethnomedical plant Desmidorchis adenensis (Deflers) Meve & Liede (syn. Caralluma. adenensis (Deflers) A.Berger) for its anti-diabetic, anti-ulcer, anti-inflammatory, anti-parasitic, and anti-pyretic properties. Its aerial parts are rich in pregnane glycosides. The purpose of this study was to assess the wound-healing potential of the total methanolic extract (DAd-TM) and mother liquor fraction (DAd-MR) from D. adenensis (Deflers) Meve & Liede in vitro and in a murine full-thickness excision wound model, focusing on oxidative stress, inflammation, and FOXO1/MIP-2 signaling pathway. In vitro, DAd-MR showed the lowest cytotoxicity (IC50&#x202f;=&#x202f;232.63&#x202f;&#xb1;&#x202f;7.88&#x202f;&#x3bc;g/mL) and the highest wound closure rate (85.19&#x202f;&#xb1;&#x202f;2.82%) in the scratch assay. In vivo, topical application of 5% DAd-TM and 5% DAd-MR for 10 days in male Swiss mice significantly accelerated wound closure to 91% and 97% (P&#x202f;<&#x202f;0.05), and compared to Mebo&#xae; (a commercial reference &#x3b2;-sitosterol-based preparation) by 41% and 52% (P&#x202f;<&#x202f;0.05). Both fractions markedly reduced malondialdehyde (MDA) levels while increasing glutathione (GSH), collagen type I, MIP-2 (a key chemokine involved in inflammatory cell recruitment), and FOXO1 (a transcription factor that regulates oxidative stress response and keratinocyte migration/re-epithelialization). Histopathological examination with semi-quantitative scoring confirmed enhanced re-epithelialization, collagen deposition, and reduced inflammation, particularly with 5% DAd-MR. The study provides the first comprehensive scientific evidence that total extract, more effectively, mother liquor of D. adenensis has skin healing potential via antioxidant, anti-inflammatory, and pro-regenerative mechanisms involving FOXO1 and MIP-2 pathways, as well as stimulating skin extracellular matrix components synthesis and reepithelialization. These findings were confirmed by histological testing. The latter was specifically investigated to enrich polar pregnane glycosides while reducing cytotoxicity associated with non-polar constituents. These findings provide scientific validation for its traditional use and highlight DAd-MR as a promising natural wound-healing agent.

Colorectal cancer (CRC) is driven by oxidative stress, chronic inflammation, and disruption of cytoprotective signaling pathways. This study aimed to evaluate whether poly(lactic-co-glycolic acid) (PLGA)-based nanoparticle delivery enhances the chemoprotective efficacy of paeonol against 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis, with a focus on modulation of the NRF2/HO-1 pathway. Sixty male Wistar rats were randomly assigned to six groups: control, paeonol (PNL), PNL-PLGA, DMH, DMH + PNL, and DMH + PNL-PLGA. CRC was induced using DMH over 10 weeks. Serum tumor biomarkers (AFP, CEA, CA19-9, CA125, CA15-3), oxidative stress markers (ROS, MDA, antioxidant enzymes), inflammatory cytokines, DNA damage, apoptosis- and autophagy-related gene expression, and hepatic and renal function were assessed. Histopathological and ultrastructural analyses of colonic tissues were performed. DMH exposure was markedly associated with increased tumor biomarkers, oxidative stress, and inflammatory mediators, DNA damage, and impaired liver and kidney function. It was also associated with the restoration of NRF2/HO-1 signaling, improved redox balance, suppression of inflammation, reduction in DNA damage, and preservation of regulated NRF2/HO-1 signaling, antioxidant defenses, autophagy markers, and apoptotic proteins, as well as severe histological and ultrastructural alterations. Free paeonol partially attenuated these changes. In contrast, PNL-PLGA was significantly associated with restoring NRF2/HO-1 signaling, improving redox balance, suppressing inflammation, reducing DNA damage, and preserving colonic architecture and ultrastructure. These findings demonstrate that a PLGA-based nanoformulation of paeonol markedly improves its chemopreventive efficacy against DMH-induced CRC, primarily by activating NRF2/HO-1 signaling and modulating oxidative stress, inflammation, apoptosis, and autophagy, highlighting its potential as a promising nanotherapeutic strategy for colorectal cancer.

Thioredoxin (Trx) is a conserved redox regulatory protein that plays critical roles in maintaining cellular redox homeostasis and immune defense. However, its molecular characteristics and antiviral functions in grass carp (Ctenopharyngodon idella) remain largely unknown. In this study, thioredoxin 1 (trx1) was cloned and functionally characterized. The full-length trx1 cDNA was 834 bp, containing a 324 bp open reading frame encoding a 107-amino-acid protein with the conserved Cys-Gly-Pro-Cys (CGPC) redox-active motif. Phylogenetic and structural analyses demonstrated that Trx1 was highly conserved among vertebrates. The trx1 transcripts were ubiquitously expressed in all tested tissues, with relatively high levels in the spleen and liver, and were significantly induced by lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (poly I:C), and grass carp reovirus (GCRV) infection. Recombinant Trx1 was successfully expressed in Escherichia coli and enhanced bacterial resistance to H2O2-induced oxidative stress. Subcellular localization analysis detected Trx1-GFP signals in the cytoplasm and nucleus of C. idella kidney (CIK) cells, with obvious nuclear enrichment after H2O2 treatment and GCRV infection. Functional analyses demonstrated that trx1 overexpression alleviated oxidative stress, inflammation, and apoptosis, accompanied by reduced GCRV replication, whereas trx1 silencing produced the opposite effects. Collectively, these findings suggest that trx1 acts as an important antiviral regulator that maintains intracellular redox homeostasis and contributes to host protection against GCRV infection by limiting oxidative stress, apoptosis, and excessive inflammatory responses.

Melatonin (Mel) exerts antioxidant and anti-ferroptosis effects not only via the canonical receptors Mt1/Mt2 but also via metabotropic glutamate receptor 1 (mGluR1)/glutamate-mediated signaling. Nevertheless, the regulatory mechanism by which Mel modulates mGluR1/glutamate signaling in retinal ischemia-reperfusion (I/R) injury and its downstream effects on ferroptosis and oxidative stress remain poorly understood. Here, bulk RNA sequencing identified that the Mel receptors Mt1/Mt2 and ferroptosis/iron-redox regulators (Gpx4, Fth1, and xCT) were significantly downregulated after retinal I/R. Mel improved retinal structural and visual function, visual-guidance behavior, and electrophysiological responses following I/R while concurrently reducing ferroptotic and inflammatory injury markers. These benefits were largely abolished by Mel membrane receptor antagonists. Mechanistically, Mel upregulated Homer1a in vivo and in vitro in a receptor-dependent manner. Conditional deletion of Homer1a in transgenic mice, as well as Homer1a knockdown in retinal ganglion cells (RGCs), abolished the protective effects of Mel on visual function, along with its anti-ferroptotic and anti-inflammatory activities. Molecular docking and immunoprecipitation assays demonstrated that Mel restored the interaction between Homer1a and mGluR1 and activated the xCT/GSH/Gpx4 antioxidant axis. Pharmacologic inhibition of xCT with the buthionine sulfoximine (BSO) simulation pr genetic interference with xCT expression counteracted the protective effects of Mel. Mel also enhanced Nrf2-mediated transcriptional expression of cCT in a Homer1a/mGluR1-dependent manner. Collectively, our results define a Mel-Homer1a/mGluR1-Nrf2/xCT signaling cascade that promotes RGCs survival after I/R by suppressing ferroptosis/iron-redox reactions, thereby providing a potential translatable strategy for receptor-targeted intervention in I/R-related retinal damage.

Lead exposure remains a pervasive environmental and public health threat, imposing a substantial burden of neurodevelopmental and cognitive dysfunction, yet safe mechanism-oriented interventions remain limited. Genistein, a soybean-derived isoflavone with antioxidant and neuroprotective potential, may counter heavy metal-induced neural injury; however, whether its efficacy is associated with redox-metabolic remodeling is unclear. Here, we evaluated genistein in lead-exposed C57BL/6J mice and lead-challenged HT22 hippocampal neurons. Genistein improved novel-arm exploration and spatial memory without altering locomotor or swimming performance, and attenuated neuronal disorganization and apoptosis in hippocampal CA1, CA3 and dentate gyrus regions. These protective effects were accompanied by reduced blood and hippocampal lead accumulation, restored glutathione redox balance, enhanced antioxidant capacity, preserved mitochondrial integrity, and suppressed Bax/Caspase-3-associated apoptotic signaling. Importantly, because genistein also reduced hippocampal lead accumulation, the in vivo neuroprotection may reflect both reduced target-tissue lead burden and improved glutathione-related redox homeostasis. Untargeted metabolomics identified 59 genistein-responsive metabolites enriched mainly in glutathione metabolism, oxidative phosphorylation, and ascorbate/aldarate metabolism, linking metabolic remodeling to behavioral recovery and reduced oxidative-apoptotic injury. In HT22 cells, blockade of glutathione synthesis by buthionine sulfoximine markedly weakened genistein-mediated cytoprotection, mitochondrial membrane potential recovery, and apoptosis inhibition. Collectively, genistein mitigates lead-induced hippocampal neurotoxicity and cognitive impairment by restoring glutathione-centered redox-mitochondrial homeostasis, supporting its further development as a mechanistically defined dietary candidate for environmental pollutant-associated neural injury.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis, are distinguished by progressive neuronal dysfunction caused primarily by oxidative stress, mitochondrial impairment, neuroinflammation, and redox imbalance. Growing evidence suggests that indole-derived compounds have significant neuroprotective potential due to their antioxidant, anti-inflammatory, and redox-modulating properties. This review summarizes the structural and biological significance of indole scaffolds, focusing on the mechanisms by which natural, endogenous, microbiota-derived, and synthetic indole compounds protect neuronal networks. Indole-3-carbinol, 3,3'-diindolylmethane, indole-3-propionic acid, and melatonin are major indole derivatives that control important neuroprotective pathways like Nrf2/ARE signaling, mitochondrial bioenergetics, neurotrophic factor expression, apoptotic regulation, and suppression of proinflammatory mediators. These compounds also maintain synaptic plasticity, reduce reactive oxygen species production, and improve neuronal survival in neurodegenerative disease models. Additionally, updated information from translational and clinical research indicates that indole-based compounds may have promising therapeutic applications; however, obstacles like low bioavailability, metabolic instability, and blood-brain barrier penetration continue to be major obstacles to clinical application. Development in nanoparticle delivery systems, microbiome-targeted interventions, and rational structural optimization may improve therapeutic efficacy and translational potential. Overall, indole-derived compounds are a versatile class of redox modulators with potential applications in the prevention and treatment of neurodegenerative diseases via integrated antioxidant and neuroprotective mechanisms.

Chronic hyperglycemia and excessive reactive oxygen species (ROS) production are defining features of endothelial dysfunction, a key driver of diabetic vascular complications such as diabetic nephropathy. Microvesicles (MV-enriched fraction), a subtype of extracellular vesicles, and the stress-responsive antioxidant protein Sestrin2 (SESN2) have emerged as important contributors to these processes. This study investigated the role of the MV-enriched fraction in endothelial cell communication under diabetic conditions, with a particular focus on oxidative stress signaling. To model diabetic injury, EA.hy926 endothelial cells were treated with methylglyoxal (MGO), and the resulting MV-enriched fraction was isolated and then applied to two recipient models: na&#xef;ve endothelial cells and SESN2 knockdown (KD) cells. Protein expression of key antioxidant markers, including endothelial nitric oxide synthase (eNOS), was assessed by Western blot. Nitric oxide (NO) bioavailability was quantified via nitrite measurement using 2,3-diaminonaphthalene (DAN), while mitochondrial and cytosolic ROS levels were evaluated using MitoSOX and dihydroethidium (DHE), respectively. Results demonstrated that the MV-enriched fraction derived from diabetic conditions triggers a complex antioxidant response in healthy endothelial cells, characterized by upregulation of SESN2, superoxide dismutase 1 (SOD1), and heme oxygenase-1 (HO-1). This suggests a compensatory mechanism that mitigates oxidative stress. Notably, SESN2 KD cells exhibited increased ROS production and reduced NO levels upon MV treatment, underscoring the essential role of SESN2 in maintaining redox homeostasis. Overall, this study highlights the dual role of the MV-enriched fraction as a mediator of both protective and detrimental redox signaling in diabetic endothelial dysfunction and suggests potential therapeutic targets for managing diabetic vascular complications.

6-Phosphogluconate dehydrogenase (6PGDH) functions in the oxidative phase of the pentose phosphate pathway (oxiPPP), together with glucose-6-phosphate dehydrogenase (G6PDH). These two enzymes play central roles in cellular NADPH generation. In pepper fruit, two genes were identified in the transcriptome, designated Ca6PGDH1 and Ca6PGDH2, which appear to encode a peroxisomal and a plastidial putative isozyme, respectively. During ripening, Ca6PGDH1 exhibited only minor changes in its expression, whereas Ca6PGDH2 was markedly downregulated. The expression patterns of both genes diverged in response to exposure to a nitric oxide (NO)-enriched atmosphere and melatonin, while both NO and melatonin treatments partially mitigated the downregulation of Ca6PGDH2 but not that of Ca6PGDH1. At the enzymatic level, the total 6PGDH activity exhibited a modest decline during ripening. Isoenzymatic analysis using non-denaturing polyacrylamide gel electrophoresis revealed three distinct isozymes, designated 6PGDH I to III, in order of increasing electrophoretic mobility. In vitro assays examining the effects of various reducing agents, including glutathione (GSH) and L-cysteine (L-Cys), as well as signaling molecules such as NO, peroxynitrite (ONOO-), hydrogen sulfide (H2S), and cyanide, showed that the NO donors and H2S exerted inhibitory effects on some isozymes, with the strongest inhibition observed for Ca6PGDH III whereas reducing compounds (GSH and Cys) protected against these inhibitory effects. Together, these results highlight Ca6PGDH as a redox-sensitive enzyme that may contribute to metabolic and signaling homeostasis during pepper fruit ripening.

Drug repurposing has emerged as a promising strategy for identifying novel anticancer agents among clinically established drugs. Fexofenadine, a second-generation H1 antihistamine, has been proposed as a candidate for repurposing in oncology; however, the molecular mechanisms underlying its biological activity remain insufficiently characterized. This study investigated the effects of fexofenadine on oxidative stress, mitochondrial function, apoptosis, and pro-survival signaling pathways in cervical and lung cancer cells. HeLa and A549 cancer cells, as well as non-tumorigenic Beas-2B epithelial cells, were exposed to fexofenadine under in vitro conditions. Cell viability, apoptosis, reactive oxygen species generation, mitochondrial membrane potential, DNA damage, autophagy-associated responses, and PI3K/AKT and MAPK/ERK pathway activation were assessed using flow cytometry, fluorescence microscopy, electron microscopy, and biochemical assays. Three-dimensional spheroid cultures and N-acetyl-L-cysteine rescue experiments were additionally employed to evaluate biological relevance and the contribution of oxidative stress. Fexofenadine induced concentration-dependent accumulation of reactive oxygen species, mitochondrial membrane depolarization, Bcl-2 inactivation, caspase-3/7 activation, DNA damage, and apoptotic cell death in HeLa and A549 cells. Antioxidant pretreatment with N-acetyl-L-cysteine significantly reduced oxidative stress, attenuated mitochondrial dysfunction, and partially suppressed apoptosis. Fexofenadine was associated with reduced PI3K/AKT and MAPK/ERK pathway activation and promoted autophagy-associated responses. In three-dimensional spheroid cultures, treatment disrupted spheroid integrity and increased apoptotic cell death. Non-tumorigenic Beas-2B cells exhibited lower sensitivity to treatment than malignant cells. Fexofenadine disrupts redox homeostasis and is associated with reduced activation of pro-survival signaling pathways, resulting in oxidative stress-associated mitochondrial dysfunction and apoptosis in cancer cells. These findings provide mechanistic support for further evaluation of fexofenadine as a candidate for anticancer drug repurposing, while additional pharmacokinetic and in vivo studies are required to determine its translational relevance.

Effective pharmaceutical interventions for treating the secondary damage associated with traumatic brain injury (TBI) are limited due to poor delivery into the brain, insufficient target engagement, and an incomplete understanding of the pathophysiological changes that occur post-impact. Thus, nanoparticles (NP), which have an enhanced permeation and retention-like effect within the perturbed blood-brain barrier, have grown as a potential candidate for treating TBI. We have investigated the antioxidant capacity of thiol-based NP, termed neuroprotective copolymers (NPC3), and their ability to neutralize reactive oxygen species (ROS) and lipid peroxidation products (LPOx). Here, we assessed the efficacy of NPC3 for alleviating the secondary injury cascade in TBI with a specific focus on ameliorating molecular and structural deficits in a mouse controlled cortical impact (CCI) model. NPC3 delivered post-CCI alleviated oxidant burden, reducing both antioxidant enzyme expression and Nrf2 activation. These changes in redox signaling resulted in a shift in metabolic function, with increased AMPK activation with NPC3 treatment. T2-weighted and diffusion magnetic resonance imaging revealed vasogenic edema formation at 30 days post-CCI and alterations in mean diffusivity, which were moderated by NPC3. Furthermore, NPC3 reduced GFAP and Iba1 at multiple impact severities, which positively correlated with urinary 8-isoprostane. Overall, this work shows NPC3 reduced glial reactivity, affected redox metabolism, and ultimately contributed to improvements in structural deficits post-CCI.

Colorimetric assays in complex food matrices are often affected by background color, turbidity and light scattering, which can mask target-induced absorbance changes and lead to false-negative results. Herein, a dual-route gold nanorod (AuNR) cascade-etching platform was developed for matrix-tolerant detection of reducing antioxidants or nitrite (NO&#x2082;&#x207b;) through different reaction pathways. In the AuNR&#x2081;-TMB-AuNR&#x2082; system, bilayer-structured AuNR&#x2081; served as an oxidase-like catalyst for TMB oxidation, while AuNR&#x2082; acted as a morphology-dependent localized surface plasmon resonance (LSPR) and photothermal transducer. Reducing antioxidants, represented by ascorbic acid (Vc), reduced oxTMB and inhibited the formation of etching-active TMB-derived species, thereby suppressing AuNR&#x2082; etching. By contrast, NO&#x2082;&#x207b; participated in an oxTMB-involved reaction pathway and promoted AuNR&#x2082; etching under acidic conditions. The two routes produced opposite signal trends. Increasing antioxidant concentration increased residual AuNR&#x2082; absorption and photothermal heating while attenuating the LSPR blue shift. Increasing NO&#x2082;&#x207b; concentration decreased AuNR&#x2082; absorption, enlarged the blue shift and reduced photothermal output. Using Vc as the reference antioxidant, the platform achieved LODs of 0.23-0.27 &#xb5;M, while NO&#x2082;&#x207b; was detected with LODs of 0.15-0.28 &#xb5;M. In milk powder matrices, direct oxTMB colorimetry was strongly affected by positive optical background, whereas AuNR&#x2082; LSPR-shift and photothermal readouts provided reliable physical signals after simple dilution. This work offers a dual-route sensing strategy that enables selective antioxidant or nitrite detection in complex food samples via pathway-specific assay conditions.

Trace metal ions regulate enzymatic catalysis, redox homeostasis, and xenobiotic metabolism across biological systems. This article examines the role of metal ions in governing sesquiterpene biosynthesis and redox signalling in Santalum album from a bioinorganic perspective. Current evidence in this review indicates that the formation of &#x3b1;- and &#x3b2;-santalol depends on magnesium-coordinated terpene synthases and iron-containing cytochrome P450 monooxygenases. In these systems, Mg2&#x207a; stabilizes diphosphate leaving groups during carbocation formation, while heme-bound Fe mediates oxygen activation and regioselective hydroxylation. Variations in Mg2&#x207a; and Fe availability may influence metabolic flux through the mevalonate pathway and alter essential oil composition. In addition, trace metals including Fe, Zn, Cu, Se, and Mg regulate antioxidant defence systems, mitochondrial respiration, apoptosis signalling, and inflammatory pathways that intersect with reported biological effects of santalol. Toxic elements such as Pb and Cd can disrupt metalloprotein function and are subject to regulatory limits under ICH Q3D guidelines. Analytical approaches including ICP-MS and laser ablation ICP-MS provide quantitative and spatial insight into elemental distribution in plant tissues. Integration of metallomic data with biochemical and molecular evidence offers a framework for understanding metal-dependent regulation of plant secondary metabolism.

Allicin, an organosulfur compound derived from garlic (Allium sativum), has been extensively studied for its cardiovascular benefits. Numerous reports highlight its lipid-lowering, antioxidant, and anti-atherogenic properties. The lipid-modulating effects reported for allicin-containing preparations are evidenced by reductions in plasma cholesterol and atherosclerotic lesion development. However, because intact allicin is highly unstable and rapidly degraded under physiological conditions, these effects should be interpreted as potentially reflecting the activity of allicin-derived organosulfur metabolites as well as allicin itself. Herein, we present a comprehensive summary of the reported anti-atherogenic effects of allicin. The impact of allicin on lipid metabolism, antioxidant defenses, and inflammatory processes is thoroughly evaluated. Studies demonstrating the ability of allicin to scavenge reactive oxygen species, prevent LDL oxidation, modulate thiol-dependent redox enzymes, and enhance endogenous antioxidant systems are outlined. Additionally, the molecular pathways underlying these effects, including NF-&#x3ba;B, NLRP3, MAPK, Nrf2, and PPAR&#x3b3;/LXR&#x3b1; signaling, are presented. Experimental evidence suggests that allicin and/or allicin-derived organosulfur metabolites may influence atherosclerosis-related processes through coordinated regulation of lipid metabolism, oxidative stress, and inflammatory responses. Nevertheless, the interpretation of these findings remains limited by poor allicin stability, uncertain systemic exposure to intact allicin, heterogeneity among garlic formulations, and inconsistent clinical outcomes. A deeper understanding of the relative contribution of intact allicin, allicin-generating formulations, and downstream metabolites is essential to evaluate their potential as natural or adjunctive therapeutic agents. Further research into its stability, bioavailability, and optimal dosage, particularly in humans, is warranted to ensure maximal therapeutic benefit towards the prevention and/or treatment of atherosclerosis.