Antioxidants最新文献

Mangosteen (Garcinia mangostana L.) has long been used in traditional Southeast Asian medicine to treat inflammatory-related conditions. In this study, three new compounds, including garcimangone A (1), garcimangone B (2), and the S-form of garcimangone C (3), and 18 known compounds were isolated and investigated for their anti-inflammatory properties and effects on M1- and M2-associated markers. Among the isolated components, γ-mangostin (5), garcinone D (6), morusignin J (15), and fuscaxanthone C (16) showed the most potent NO-inhibitory effects in LPS-stimulated RAW264.7 cells. SAR study revealed that chromeno moiety at C-3,4, oxygen substituents at C-1,3,6,7, and isoprenyl groups at C-2,8 are key structural features that promoted anti-inflammatory activity. Cytokine analysis results indicated that morusignin J (15) and fuscaxanthone C (16) could modulate the production of pro-inflammatory cytokines, such as TNF-α and IL-6, while modulating the anti-inflammatory cytokine IL-10. Western blot results demonstrated that morusignin J (15) modulated the inflammatory response through NF-κB and MAPK signaling and increased the expression of M2-associated markers KLF4 and arginase-1 in LPS-induced RAW264.7 macrophages. Further molecular docking analysis confirmed the high binding affinity of morusignin J (15) with key iNOS residues, such as Gln257, Pro344, Glu371, and Hem901, and the in silico prediction supported its potent oral bioavailability and drug-likeness. These in vitro and in silico findings highlight that pericarps of G. mangostana possess potential as promising natural sources for functional extracts and bioactive constituents for the development of antioxidative and anti-inflammatory candidates, and warrant further in vivo investigation in the future.

The biological effects of radiofrequency electromagnetic fields (RF-EMFs) remain an unresolved scientific issue with important societal relevance, particularly in the context of the global deployment of fifth-generation (5G) wireless technologies. The skin is continuously exposed to both RF-EMFs and ultraviolet (UV) radiation, a well-established inducer of oxidative stress and DNA damage, making it a relevant model for assessing combined environmental exposures. In this study, we investigated whether post-exposure to 5G RF-EMFs (3.5 and 28 GHz) modulates ultraviolet A (UVA)-induced genotoxic stress in human keratinocytes (HaCaT) and murine melanoma (B16) cells. Post-UV RF-EMF exposure significantly reduced DNA damage markers, including phosphorylated histone H2AX (γH2AX) foci formation (by approximately 30-50%) and comet tail moments (by 60-80%), and suppressed intracellular reactive oxygen species (ROS) accumulation (by 56-93%). These effects were accompanied by selective attenuation of p38 mitogen-activated protein kinase (MAPK) phosphorylation (reduced by 55-85%). The magnitude of molecular protection was comparable to that observed with N-acetylcysteine treatment or pharmacological inhibition of p38 MAPK. In contrast, RF-EMF exposure did not reverse UV-induced reductions in cell viability or alterations in cell cycle distribution, indicating that its protective effects are confined to early molecular stress-response pathways rather than downstream survival outcomes. Together, these findings demonstrate that 5G RF-EMFs can facilitate recovery from UVA-induced molecular damage via redox-sensitive and p38-dependent mechanisms, providing mechanistic insight into the interaction between modern telecommunication frequencies and UV-induced skin stress.

This study investigated the effects of encapsulated capsaicinoids (CAPs), containing 0.47% capsaicin and 0.22% dihydrocapsaicin, on growth, serum parameters, nutrient digestibility, and intestinal health in weaned piglets. A total of 168 piglets were randomly assigned to four groups: a basal diet or the same diet supplemented with 200 (LDC), 400 (MDC), or 600 (HDC) mg/kg of CAPs. The results indicated that CAPs improved lipid metabolism, evidenced by higher crude fat digestibility in the LDC and MDC groups and reduced serum low-density lipoprotein cholesterol in all CAP groups compared to the control. Glutathione peroxidase activity was significantly higher in the MDC and HDC groups. Histological analysis showed reduced hepatic vacuolation, enlarged fungiform papillae with shallower taste pores in the tongue epithelium, and deeper ileal crypts in the LDC group. At the molecular level, ZO-1 expression in the ileum was significantly upregulated in LDC piglets. Colonic microbiota analysis revealed decreased relative abundances of Lachnospiraceae_AC2044_group, Lachnospiraceae_XPB1014_group, and Rikenellaceae_RC9_gut, while Butyricicoccus was significantly enriched in the LDC group. In conclusion, CAPs supplementation enhanced fat digestibility, lipid metabolism, antioxidant capacity, intestinal development, and colonic microbiota composition, with the 200 mg/kg dose showing the most pronounced effects.

Peripheral nerve injuries affect 13-23 out of 100,000 people annually, with Wallerian degeneration and subsequent inflammatory/oxidative responses critically impacting recovery. Aloperine, a natural alkaloid from Sophora alopecuroides L., exhibits potent anti-inflammatory and antioxidant properties but has never been studied for nerve repair. In this study, we aimed to investigate whether aloperine could enhance peripheral nerve regeneration by modulating inflammation and oxidative stress in a rat sciatic nerve injury model. Thirty male Wistar rats underwent sciatic nerve neurotmesis with epineural repair. Animals were divided into surgical controls (Group A), aloperine-treated rats (Group B; single 100 mg/kg intraperitoneal dose), and intact controls (Group C). After 8 weeks, outcomes were assessed via functional tests (pinprick, hot plate, extensor postural thrust), biochemical analyses (TNF-α, IL-6, IL-10, TOS/TAS), and histomorphometric evaluations (axon counts, diameter indices, immunohistochemistry). Aloperine treatment significantly improved functional recovery, with near-normal hot plate latency and motor performance. Biochemically, it reduced pro-inflammatory markers (TNF-α) while elevating IL-10. Oxidative stress was attenuated. Histologically, treated nerves showed better-preserved axonal architecture (reduced inflammation). This first investigation of aloperine for nerve repair demonstrates its therapeutic potential through dual anti-inflammatory and antioxidant mechanisms, significantly improving functional and structural outcomes. These findings support its development as a novel treatment for peripheral nerve injuries.

To date, neutrophil-derived myeloperoxidase (MPO), a key mediator of inflammation and oxidative stress, has predominantly been assessed in peripheral fluids by protein concentration rather than enzymatic activity, mainly due to methodological limitations. However, MPO activity directly reflects the enzyme's cytotoxic potential and pathogenic role in inflammatory diseases. To address this gap, we employed an optimized immunocapture assay to evaluate MPO activity, specific activity, and protein concentration in females with type 2 diabetes mellitus (T2DM), a condition tightly linked to chronic low-grade inflammation and obesity. Our findings revealed that females with T2DM exhibited nearly three-fold higher serum MPO activity and more than two-fold greater specific activity compared to controls with no differences in MPO protein concentration. Notably, MPO-specific activity remained significantly associated with T2DM (p < 0.01 to p < 0.001 across multivariate models), even after adjusting for age and dual-energy X-ray absorptiometry-derived measures of total and regional fat mass. Only android/gynoid fat distribution retained marginal significance in these models. This study is the first demonstration that MPO enzymatic activity, rather than protein concentration, is independently linked to T2DM in females. These findings underscore the importance of assessing functional MPO activity in the context of metabolic disease and support its potential role as a pathophysiological marker.

Isothiocyanates (ITCs) are well-known electrophilic agents with antioxidant and anticancer properties, largely attributed to their ability to activate the Nrf2/ARE pathway. Building on previous work with C1-ITC glycosyl derivatives, we designed and synthesized a new series of S-glycosyl isothiocyanates in which the ITC group was repositioned to the C6 carbon of the glucose scaffold. This structural rearrangement yielded stable and synthetically accessible derivatives with markedly enhanced biological profiles. Several compounds showed potent Nrf2 activation at non-cytotoxic concentrations, with CD values comparable to or exceeding those of natural ITCs. In parallel, the new C6-ITC derivatives displayed significant antiproliferative activity against leukemia and solid tumor cell lines. Among them, the phenylsulfone derivative 13 emerged as a particularly promising dual-action molecule, combining strong Nrf2 induction with low-micromolar cytotoxicity. Molecular docking was used as a hypothesis-generating approach and suggested a possible interaction with the STAT3 SH2 domain, although further studies are needed to validate this target. Overall, these results support glucose-based ITCs as a versatile platform for the development of multifunctional antioxidants with complementary anticancer properties.

Metabolic bariatric surgery (MBS) induces substantial metabolic, inflammatory, and nutritional changes that can alter hemostatic balance through redox-dependent mechanisms. This systematic review evaluated coagulation disturbances after MBS with emphasis on oxidative stress and micronutrient deficiencies. A structured search of PubMed, Scopus, and Web of Science (2000-2025) identified 1707 records; 21 studies met inclusion criteria. Available evidence suggests that although MBS reduces obesity-related inflammation and oxidative burden in many patients, a proportion of individuals may present with persistent redox imbalance, elevated D-dimer or vWF (von Willebrand Factor), and delayed normalization of fibrinolysis. Micronutrient deficiencies-particularly vitamins K, B12, folate, selenium, zinc, and copper-are common after malabsorptive procedures and contribute to both thrombotic and hemorrhagic complications by impairing antioxidant defenses, endothelial function, and vitamin K-dependent coagulation pathways. Postoperative venous thromboembolism (VTE) incidence ranges from 0.3 to 0.5%, with higher risk after Roux-en-Y gastric bypass than sleeve gastrectomy, while bleeding is primarily associated with vitamin K deficiency, marginal ulcers, and anticoagulant exposure. The findings underscore the interdependence of oxidative stress, nutritional status, and hemostasis after MBS. Individualized thromboprophylaxis, routine detection of micronutrient deficiencies, and long-term biochemical monitoring are essential to maintain hemostatic stability. Standardized redox-hemostasis biomarker panels are needed to clarify mechanistic pathways and improve postoperative preventive strategies.

Melamine, a nitrogen-rich industrial chemical, has raised increasing concern as an emerging environmental contaminant with potential reproductive toxicity. While its nephrotoxic effects are well established, the direct impact of melamine on human sperm remains poorly defined. In this study, we investigated the in vitro effects of melamine on human sperm, under both capacitating and non-capacitating conditions. Functional analyses revealed that the exposure to 0.8 mM melamine, the highest non-cytotoxic concentration in vitro, significantly compromised sperm motility and disrupted key capacitation processes, including tyrosine phosphorylation patterns, cholesterol efflux, and the acrosome reaction. Molecular assessments demonstrated melamine-induced mitochondrial dysfunction, characterized by COX4I1 downregulation, reduced mitochondrial membrane potential, and altered reactive oxygen species production. In parallel, gene expression analyses revealed the activation of apoptotic pathways, with the upregulation of BAX and downregulation of BCL2, changes that were more pronounced during capacitation. Furthermore, melamine exposure significantly increased sperm DNA fragmentation and denaturation, indicating genotoxic stress. Collectively, these findings demonstrate that even low, non-cytotoxic concentrations of melamine compromise sperm function by disrupting capacitation, mitochondrial activity, and genomic integrity. This study identifies capacitation as a critical window of vulnerability and underscores the need to consider melamine as a potential environmental risk factor for male reproductive health.

Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.

Parkinson's disease is the second leading neurodegenerative disease of aging. For over five decades, oral levodopa has been used to manage the progressive motor deficits that are the hallmark of the disease. However, individual dose requirements are highly variable, and patients typically require increased levodopa dosage as the disease progresses, which can cause undesirable side effects. It has become increasingly apparent that the gut microbiome can have a major impact on the metabolism and efficacy of therapeutic drugs. In this Perspective, we examine recent studies highlighting the impact of metabolism by Enterococcus faecalis, a common commensal gut bacterium, on levodopa bioavailability. E. faecalis expresses a highly conserved tyrosine decarboxylase that promiscuously converts levodopa to dopamine in the gut, resulting in decreased neuronal uptake of levodopa and reduced dopamine formation in the brain. Mitochondria-targeted antioxidants conjugated to a triphenylphosphonium moiety have shown promise in transiently suppressing the growth of E. faecalis and decreasing microbial levodopa metabolism, providing an approach to modulating the microbiome that is less perturbing than conventional antibiotics. Thus, mitigating metabolism by the gut microbiota is an attractive therapeutic target to preserve and potentiate the efficacy of oral levodopa therapy in Parkinson's disease.