Antioxidants最新文献

Allergic rhinitis (AR) is characterized by persistent epithelial remodeling, yet the upstream drivers and molecular mechanisms remain poorly defined. Analysis of nasal mucosa from AR patients revealed marked epithelial remodeling, oxidative stress, and Th2 inflammation. Transcriptome analysis of nasal mucosa revealed RhoA as one of the most upregulated genes, with expression positively correlating with disease severity. Using epithelial-specific RhoA-deficient mice (RhoA^cKO) and fasudil, a RhoA/ROCK inhibitor, we found that loss of RhoA/ROCK signaling markedly attenuated nasal Th2 inflammation, oxidative stress, and epithelial remodeling following allergen challenge. Further transcriptome analysis demonstrated that elevated RhoA activation was associated with increased epithelial cellular senescence. Both in vitro and in vivo studies confirmed that epithelial RhoA activation promotes allergen- or Th2 cytokine-induced cellular senescence, whereas genetic or pharmacologic elimination of senescent cells alleviated allergic inflammation and tissue remodeling. Pathway analysis identified PRKN (parkin) as a central node within RhoA-regulated, senescence-associated networks in AR. Functional studies showed that PRKN overexpression mitigated IL-13-induced mitochondrial dysfunction, oxidative stress, and epithelial senescence in human nasal epithelial cells. Together, these findings reveal that RhoA-driven epithelial senescence contributes to allergic inflammation and epithelial remodeling in AR and identify PRKN as a potential therapeutic target to restore epithelial homeostasis.

Chronic sleep deprivation (CSD) disrupts redox homeostasis and enhances neuroinflammatory activation, contributing to progressive cognitive impairment. Propyl gallate (PG), a lipophilic ester of gallic acid with established antioxidant activity, has not been investigated in the context of prolonged sleep deprivation. The current study examined whether PG alleviates CSD-induced oxidative imbalance, inflammatory activation, and associated behavioral deficits. Male ICR mice were subjected to 14 days of CSD using a rolling-drum apparatus and received oral PG (50, 100, or 200 mg/kg) or Ginkgo biloba extract (GBE, 40 mg/kg). Behavioral outcomes were assessed through a battery of tests, including the open-field, novel-object recognition, step-through, and Morris water maze paradigms. Oxidative and inflammatory biomarkers were assessed in serum and hippocampus, and Western blotting quantified the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2). PG improved CSD-induced impairments in exploration, recognition memory, and spatial learning; restored antioxidant capacity; reduced lipid peroxidation; enhanced Nrf2-associated antioxidant signaling; and suppressed NF-κB-mediated inflammatory activation. These findings indicate that PG alleviates cognitive deficits induced by CSD through the modulation of redox homeostasis and neuroinflammatory responses, supporting its potential as an antioxidant derivative under chronic sleep-deprivation conditions.

Mitochondrial dysfunction and oxidative stress are crucial contributors to the pathogenesis of Alzheimer's disease (AD) and dementia exhibiting cognitive decline at the early stage of neurodegeneration. Natural vitamin antioxidants (NVAs) and novel mitochondria-targeted antioxidants (MTAs) are proposed as potential therapeutics though conclusive evidence is lacking. Objectives were to examine in vivo evidence on NVAs and MTAs for preventing and/or treating cognitive decline leading to dementia, to identify the most promising antioxidants, and highlight translational gaps. Methods followed PRISMA-ScR guidelines. MEDLINE, EMBASE and Scopus were searched for English language in vivo experiments assessing NVAs or MTAs in AD and dementia. A total of 25 studies (13 NVAs; 12 MTAs) met inclusion criteria. NVAs (Vitamin A, B, C, E) demonstrated mixed efficacy in reducing oxidative stress and improving cognitive outcomes, with Vitamin E showing the most consistent neuroprotective effects. MTAs (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics and cognitive performance and reduced dementia-related pathology. Both NVAs and MTAs improved biomarker profiles and cognitive outcomes in vivo animal models of AD and dementia, but MTAs showed more robust and consistent efficacy by directly targeting mitochondrial pathways. Given the favourable safety profiles of MTAs in other clinical conditions, early-phase human trials in dementia and AD are warranted to evaluate their long-term cognitive benefits.

Current pharmacotherapies against atherosclerotic cardiovascular disease are associated with considerable residual risk, together with various adverse side effects. Nutraceuticals, such as resveratrol (RSV), with excellent safety profile, represent promising alternatives and potential treatment. However, the full spectrum of anti-atherogenic actions regulated by RSV and the underlying molecular mechanisms remain poorly understood. The objective of this study therefore was to investigate the impact of RSV on key atherosclerosis-associated processes in monocytes, macrophages, endothelial cells, and smooth muscle cells in vitro, as well as in LDL receptor-deficient mice fed a high-fat diet in vivo. RSV produced beneficial changes in the plasma lipid profile and peripheral blood lymphoid cells in vivo. RSV also attenuated plaque inflammation by decreasing macrophage and T cell content and enhanced markers of plaque stability, with increased levels of smooth muscle cells and collagen content. In vitro, RSV inhibited chemokine-driven monocyte migration, inflammasome activation, matrix metalloproteinase activity, pro-inflammatory gene expression, reactive oxygen species production, and smooth muscle cell invasion. RNA-sequencing of the thoracic aorta revealed key genes and pathways mediating the antioxidant, anti-inflammatory and plaque-stabilising activities of RSV. These studies provide novel mechanistic insights on the anti-atherogenic actions of RSV and support further evaluation in human clinical trials.

Neurodegenerative diseases (NDDs), defined by the progressive loss of neurons, present a major challenge to global health. Oxidative stress and lysosomal dysfunction are both key pathogenic factors in NDDs, and they do not operate in isolation; instead, the vicious cycle they form, often mediated through organellar crosstalk, serves as the core driver of the pathological progression of NDDs, collectively worsening disease outcomes. Specifically, excessive reactive oxygen species (ROS) can disrupt lysosomal membrane integrity through lipid peroxidation and inhibit the activity of vacuolar ATPase (V-ATPase), ultimately leading to impaired lysosomal acidification. Meanwhile, lysosomal dysfunction hinders the clearance of damaged mitochondria (the primary endogenous source of ROS), toxic protein aggregates, and free iron ions. This further exacerbates ROS accumulation and accelerates neuronal degeneration. Conventional therapeutic approaches have limited efficacy, primarily due to the challenges in crossing the blood-brain barrier (BBB), insufficient targeting ability, and an inability to effectively intervene in this pathological loop. Nanotherapeutics, leveraging their tunable physicochemical properties and modular functional design, represent a transformative strategy to address these limitations. This review systematically elaborates on the reciprocal interplay between oxidative stress and lysosomal dysfunction in NDDs, with a particular focus on the central role of lysosome-mitochondria axis dysfunction, critically appraises recent advances in nanotechnology-based targeted therapies, and thereby provides a comprehensive theoretical framework to guide the development of novel NDD therapeutics.

In vitro manipulation of human spermatozoa during Assisted Reproductive Technology (ART) can induce several damages to sperm structure and functions. This study investigated the protective effects of Raphanus sativus seed extract and its active compounds on several sperm parameters during in vitro incubation and cryopreservation. Extracts from five seed-batches were characterized by HPLC-DAD-MS and ¹H-NMR, identifying sinapine and sinipic glycosides as the main characteristic compounds. Sperm DNA fragmentation (sDF) was detected by the Sperm Chromatin Dispersion test and LiveTUNEL. Excessive reactive oxygen species (ROS) production was detected by MitoSOX Red in viable spermatozoa. Caspase activity was detected by FLICA. Cryopreservation was conducted with two alternative freezing media. In vitro incubation with the extract protected against the loss of motility and reduced the induction of sDF, sperm ROS production, and caspase activity. Similarly, during cryopreservation, it allowed much better recoveries of sperm viability, motility, and DNA integrity by decreasing sperm ROS production with both freezing media. Sinapine and sinapic acid completely mimicked the protective effects of the whole extract during both in vitro incubation and cryopreservation, suggesting that they are included among the active principles. These findings support Raphanus sativus seed extract and its active compounds as candidates for inclusion in handling and freezing media for human spermatozoa in ART.

Periodontitis is a chronic non-communicable inflammatory disease in which oxidative stress plays an important role in tissue destruction and alveolar bone loss. Excessive production of reactive oxygen species disrupts redox homeostasis, activates inflammatory signaling pathways, and promotes regulated cell death processes such as pyroptosis and ferroptosis. The Nrf2/Keap1 pathway is a key regulator of antioxidant defense and cellular adaptation to redox imbalance. Impaired Nrf2 signaling has been associated with enhanced oxidative injury, NF-κB and NLRP3 inflammasome activation, osteoclast-driven bone resorption, and reduced regenerative capacity in periodontal tissues. Experimental studies suggest that Nrf2 activation can restore the redox balance and attenuate inflammation and bone destructive responses in a periodontal model. Moreover, therapeutic approaches involving phytochemicals, microbial-derived metabolites, and redox-responsive biomaterials have been reported to influence Nrf2-related signaling in experimental settings. However, the majority of the available evidence is derived from in vitro or animal studies, and the relevance of these findings to clinical periodontitis remains to be established. This review summarizes the current advances linking oxidative stress, redox signaling, cell death pathways, and bone remodeling with Nrf2 dysfunction in periodontitis and outlines the key mechanistic insights while highlighting the existing knowledge gaps.

Psoriasis is a common inflammatory skin disease with chronic manifestation in which the role of neutrophil extracellular traps (NETs) and alarmins are increasingly recognized as contributors to systemic and cutaneous inflammation. However, the interaction between alarmins and NET-driven immune responses remains poorly defined. The main aim of this study is to define the role of target alarmins (i.e., IL-33 and TSLP) in NETs induction and its subsequent impact on oxidative stress and inflammation in the peripheral blood. In the present study, we recruited active psoriasis patients (n = 56) and control (n = 56) subjects. The frequency of circulating neutrophils, the levels of NET-associated markers (MPO (myeloperoxidase)-DNA complex, CitH3 (citrullinated histone H3), PAD4 (peptidyl arginine deiminase4), NADPH oxidase, and NE (neutrophil elastase)), and alarmin transcripts (IL (interleukin)-33, TSLP (thymic stromal lymphopoietin), S100A7, S100B, HSP (heat shock protein) 60/70 were quantified using flow cytometry, ELISA (Enzyme-linked immunosorbent assay), and qPCR (quantitative polymerase chain reaction), respectively, in each group. The NET formation potential of isolated neutrophils was assessed in the presence or absence of rhIL-33 and rhTSLP by immunocytofluorescence. The effect of rhIL-33- and rhTSLP-primed NETs in augmenting oxidative stress and inflammation was evaluated on peripheral blood mononuclear cells (PBMCs) by ELISA. Significantly higher circulating neutrophils (p < 0.001) and levels of NET-associated markers (i.e., MPO-DNA complex, CitH3, PAD4, NADPH oxidase, and NE) were observed in active psoriasis patients compared to controls. Lesional skin exhibited strong expression of MPO (p < 0.001) compared to normal skin. The alarmins, IL-33 and TSLP, were markedly upregulated in the blood and skin (p < 0.05). The rhIL-33 and rhTSLP treated neutrophils demonstrated enhanced NETosis in patients (p < 0.001). Increased expression of inflammatory cytokines and oxidative stress markers were reported in PBMCs when incubated with rhIL-33- and rhTSLP-primed NETs. Taken together, our investigation demonstrated the novel mechanism wherein the alarmins IL-33 and TSLP exacerbate NET formation that may drive enhanced inflammation and oxidative stress in psoriasis.

Pyroptosis is a type of programmed cell death (PCD) with pro-inflammatory properties, which is characterized by the swelling with bubbles and the release of LDH and inflammatory cell cytokines. Polyphyllin II (PPII) is the main active ingredient of the Chinese herb Rhizoma Paridis and has been proven to exert high efficacy against a variety of malignant tumors. At present, the anti-tumor research on PPII mainly focuses on apoptosis that is an anti-inflammatory type of PCD, but other potential modes of death cell death and mechanisms of PPII remain to be discovered. Here, we first found that PPII could effectively inhibit the growth of hepatocellular carcinoma (HCC) cells via pyroptosis. After treatment with PPII, the morphology of swelling with bubbles and the formation of pores in the cell membrane in HCC cells were observed, and LDH and cell cytokines (IL-1β, IL-18, IL-6, TNF-α, IFN-β, and IFN-γ) were released. Furthermore, the flow cytometry results showed that PPII could activate oxidative stress by increasing Ca²⁺ influx, thereby promoting the production of ROS to exert anti-tumor effects. RNA sequencing revealed that pyroptosis is closely linked to several signaling pathways, including the MAPK, TNF, Rap1, mTOR, and FoxO pathways, as well as the PD-L1 expression and PD-1 checkpoint pathway. An in vivo study demonstrated that PPII treatment suppressed liver tumor growth in mice by pyroptosis in a dose-dependent manner, and it showed no obvious side effects within a certain range. The Western blot results of tumor tissues revealed that the pyroptosis effect of PPII on liver cancer was associated with the activation of the NLRP3/Caspase1/GSDMD pathway, which upregulates the expression of NLRP3, Cleaved-Caspase 1, GSDMD-N, IL-1β, and IL-18 proteins and downregulates the expression of pro-Caspase 1 and GSDMD proteins. In summary, our findings revealed the pyroptosis effect and mechanism of PPII in HCC cells in vitro and in vivo, suggesting that PPII may be used as a potential pyroptosis inducer for HCC treatment in the future.

Myocardial fibrosis (MF) is a common pathological feature of diverse cardiac disorders and is a key driving factor of cardiac dysfunction. It is marked by excessive deposition of extracellular matrix (ECM) proteins, particularly collagen type I and III, and a prolonged activation of cardiac fibroblasts. However, the molecular drivers of this process remain undetermined. Ferroptosis is an iron-catalyzed, lipid-peroxidation-dependent mode of regulated cell death. Research indicates that ferroptosis is significantly involved in the onset and advancement of MF; consequently, developing therapies that selectively modulate ferroptosis presents a promising direction of treatment options. Therefore, this paper systematically discusses the mechanisms associated with ferroptosis to explore the link between ferroptosis and MF from multiple dimensions, including iron metabolism disorders, lipid peroxidation, imbalance of glutathione metabolism, and the dysregulated activation of ferroptosis regulatory pathways, to provide innovative perspectives for the study of the specific molecular mechanisms and treatment of MF. Method: By retrieving the literature on the mechanism of ferroptosis in MF published in PubMed and Web of Science databases from 2020 to July 2025, the mechanism of action was systematically analyzed and reviewed.