Antioxidants最新文献

Although oxidants are known to be deleterious for cellular homeostasis by oxidizing macromolecules like DNA or proteins, they are also involved in signaling processes essential for cellular proliferation and survival. Here, we investigated the role of superoxide anion (O₂^-) and hydrogen peroxide (H₂O₂) homeostasis for the proliferation and survival of classical Hodgkin's lymphoma (cHL) cell lines. Inhibition of NADPH oxidases (NOX) using apocynin (Apo) and diphenylene iodonium (DPI), or treatment with the antioxidant butylated hydroxyanisole (BHA), significantly reduced proliferation and induced apoptosis in HL cell lines. These effects correlated with transcriptomic alterations involving redox regulation, immune signaling, and cell cycle control. Interestingly, treatment with DPI or antioxidants attenuated constitutive Signal Transducer and Activator of Transcription (STAT) activity, as seen by decreased phospho-STAT6 levels and reduced STAT6 DNA binding. This suggests a sensitivity of the Janus kinase (JAK)/STAT pathway in cHL cell lines to O₂^- and H₂O₂ depletion. Functional assays confirmed this by demonstrating partial restoration of proliferation or apoptosis in L428 cells that expressed constitutively active STAT6 or were transfected with small interfering RNAs (siRNAs) that targeted STAT regulators. These findings highlight that oxidants, particularly H₂O₂, act as both general oxidative stressors and essential modulators of oncogenic signaling pathways. Specifically, maintenance of oxidant homeostasis is critical for sustaining JAK/STAT-mediated growth and survival programs in cHL cells. Targeting redox homeostasis might offer a promising therapeutic strategy to impair JAK/STAT-driven proliferation and survival in cHL.

Plant byproducts represent a valuable and underutilized source of bioactive compounds. Among these, phenolic compounds have attracted growing interest from the agricultural, cosmetic, and food industries due to their diverse biological activities. These naturally occurring compounds are derived from various plant species, and they exhibit strong antioxidant, antimicrobial, and antiviral properties. Their yield, as well as quality and bioavailability, has improved with more recent advancements within green extraction, as well as purification and characterization techniques. Several phenolic compounds exhibit strong antiviral and antioxidant activities, which are highlighting their value as bioactive compounds. It is essential to evaluate extraction methods for high-yield phenolic compounds from plant byproducts so that they can contribute to the circular bioeconomy, reduction in environmental waste, and development of biomedical and food industrial applications. Their physicochemical characteristics and potential applications may lead to a determination by contributing to promising fields through expanded in vitro, in vivo, and in silico experiments. This review summarizes current research on the extraction, recovery, and applications of phenolic compounds derived from plant byproducts, providing new insights into their sustainable utilization and bioactive potential.

Plant extracts are rich in various bioactive compounds, such as polyphenols, flavonoids, tannins, terpenoids, phenolic acids, saponins, alkaloids, and polysaccharides. Antioxidant polyphenols are increasingly attracting attention, not only as dietary components but also as valuable food industry byproducts. Resveratrol, present in a wide range of plants, is well recognized for its diverse biological activities, including antioxidant, antitumor, cardioprotective, and neuroprotective effects. Given the importance of intercellular communication in these physiological processes, gap junctions (GJs) composed of connexin (Cx) family proteins are of particular interest because they provide a direct pathway for electrical and metabolic signaling and are key players in maintaining normal organ function and cell development. Aberrations of GJ intercellular communication (GJIC) may result in the progression of cardiovascular and neurological diseases and tumorigenesis. Cx43 and Cx45 play crucial roles in cardiac excitation and contraction, and alterations in their expression are associated with disrupted impulse propagation and the development of arrhythmias. In this study, for the first time, we performed a comparative analysis of the effect of resveratrol on Cx43 and Cx45 GJIC using molecular modeling, a dual whole-cell patch-clamp technique to directly measure GJ conductance (g_j), and other approaches. Our results revealed that resveratrol accomplished the following: (1) inhibited GJ g_j in Cx43- but enhanced it in Cx45-expressing HeLa cells; (2) exerted dose- and time-dependent changes in Cx expression and plaque size; (3) reduced cell viability and proliferation; (4) and altered Cx43 phosphorylation patterns linked to gating and plaque stability. Overall, resveratrol modulates GJIC in a dose-, time-, and connexin type-specific manner.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder marked by progressive kidney enlargement and cyst formation, often resulting in end-stage renal disease (ESRD). Oxidative stress (OxS) significantly contributes to renal damage in chronic kidney disease (CKD) and ADPKD. While the Mediterranean diet (Med-diet) is known for its antioxidative and anti-inflammatory effects, its impact on OxS in ADPKD remains unclear. This study aimed to assess the relationship between adherence to the Med-diet, OxS levels, and renal function in ADPKD patients. We enrolled 63 ADPKD patients aged 18-70 years with CKD stages G2-G4. Adherence to the Med-diet was evaluated using the PREDIMED questionnaire. OxS markers (NOX2-derived peptide [sNOX2-dp] and hydrogen peroxide [H₂O₂]) were measured via ELISA. Correlations between these markers, Med-diet adherence, serum creatinine, and estimated glomerular filtration rate (eGFR) were analyzed. Higher adherence to the Med-diet was associated with significantly lower OxS markers (sNOX2, p < 0.001; H₂O₂, p = 0.04). Reduced NOX2 and H₂O₂ levels correlated with lower creatinine and higher eGFR (NOX2, p < 0.001; H₂O₂, p < 0.001), suggesting an inverse relationship between OxS and renal function. In conclusion, adherence to the Mediterranean diet appears to be associated with lower levels of oxidative stress and may slow the progression of chronic kidney disease. These findings suggest that dietary interventions could mitigate disease progression by modulating OxS. Further studies are needed to confirm these results and explore the long-term effects of the Med-diet on disease progression.

Acute liver injury (ALI) is a potentially life-threatening condition lacking effective clinical drugs. Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of both inflammation and metabolism. In ALI, HIF-1α expressions are upregulated, but the role of HIF-1α in hepatocytes and whether it can be targeted remain unclear. Herein, clinical samples and ALI murine models including lipopolysaccharide/D-galactosamine (LPS/D-GalN), acetaminophen (APAP), and thioacetamide (TAA) revealed an increase in HIF-1α expression and ferroptosis. Using HIF-1α gain and loss of function mouse and hepatocyte culture models, we demonstrated that HIF-1α upregulation exacerbated liver ferroptosis and injury. Mechanistically, HIF-1α/transferrin receptor protein 1 (TFR1) axis drives hepatic iron overload, promoting ferroptotic cell death and liver injury. In addition, TFR1 inhibition reversed HIF-1α-induced ALI. Importantly, pharmacological inhibition of HIF-1α and TFR1 significantly reduced ferroptosis and mitigated liver injury both in vivo and in vitro. Together, our findings demonstrate the pathological role of hepatic HIF-1α, which may serve as a promising target of therapeutic intervention.

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a multifactorial liver disease in which mitochondrial dysfunction, oxidative stress, and inflammation play key roles in driving the progression toward metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Dysfunctional mitochondria generate excess reactive oxygen species (ROS), impair antioxidant defenses, activate pro-inflammatory pathways and hepatic stellate cells, and perpetuate liver injury. Mitochondrial Complex I is a major ROS source, particularly under conditions of dysregulated energy metabolism. Since Complex I inhibition by metformin was shown to reduce ROS and activate the adenosine monophosphate-activated protein kinase (AMPK), this study aimed to evaluate whether a novel Complex I Modulator (CIM, BI4500) could attenuate oxidative stress, inflammation, and consequently reduce lipid accumulation and fibrosis in a methionine- and choline-deficient diet (MCD)-fed rat model of MASH.

Methods: Rats were fed an MCD or an isocaloric control diet for six weeks. From week four, animals received daily oral treatment with CIM (10 mg/kg) or vehicle (Natrosol). At the endpoint, liver tissue was collected for histological, biochemical, and molecular analyses. Lipid droplet area, inflammatory infiltration, and collagen deposition were evaluated on tissue sections; total lipid content and oxidative stress markers were assessed in homogenates and isolated mitochondria. Molecular pathways related to oxidative stress, lipid metabolism, and fibrosis were assessed at protein and mRNA levels.

Results: CIM treatment significantly reduced oxidative stress (ROS, lipid peroxidation, nitrogen species), promoting AMPK activation and metabolic reprogramming. This included increased expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its target genes, and decreased sterol regulatory element binding protein-1c (SREBP-1c)-driven lipogenesis. These changes halted fibrosis progression, as confirmed by Picro-Sirius Red staining and fibrosis markers.

Conclusions: these findings indicate that Complex I modulation may represent a promising strategy to counteract MASLD progression toward MASH.

The enteric nervous system (ENS) constitutes a highly organized and intricate neuronal network comprising two principal plexuses: myenteric and submucosal. These plexuses consist of neurons and enteric glial cells (EGCs). Neurons ensure innervation throughout the intestinal wall, whereas EGCs, distributed within the mucosa, contribute to epithelial barrier integrity and modulation of local inflammatory responses. The ENS orchestrates essential gastrointestinal functions, including motility, secretion, absorption, vascular regulation, and immune interactions with gut microbiota. Under physiological conditions, intestinal homeostasis involves moderate generation of reactive oxygen species (ROS) through endogenous processes such as mitochondrial oxidative phosphorylation. Cellular antioxidant systems maintain redox equilibrium; however, excessive ROS production induces oxidative stress, promoting EGCs activation toward a reactive phenotype characterized by pro-inflammatory cytokine release. This disrupts neuron-glia communication, predisposing to enteric neuroinflammation and neurodegeneration. Obesity, associated with hyperglycemia, hyperlipidemia, and micronutrient deficiencies, enhances ROS generation and inflammatory cascades, thereby impairing ENS integrity. Nevertheless, non-pharmacological strategies-including synthetic and natural antioxidants, bioactive dietary compounds, probiotics, and prebiotics-attenuate oxidative and inflammatory damage. This review summarizes preclinical and clinical evidence elucidating the interplay among the ENS, obesity-induced oxidative stress, inflammation, and the modulatory effects of antioxidant interventions.

Tris(1-chloro-2-propyl) phosphate (TCIPP) is an emerging environmental pollutant associated with adverse respiratory effects, yet whether niacin has a protective effect on lung function remains unclear. Data from 1031 participants in the 2011-2012 National Health and Nutrition Examination Survey (NHANES) were analyzed using multiple linear regression to assess associations between urinary bis(1,3-dichloro-2-propyl) phosphate (BCIPP), dietary niacin intake, and pulmonary function. Animal models were established to investigate TCIPP-induced lung injury and the protective effects of niacin. Lung injury was assessed by histopathology, lung function, inflammation, and oxidative stress-related indicators. Comparative Toxicogenomics Database (CTD), molecular docking, and Western blot were performed to explore underlying mechanisms. Higher urinary BCIPP concentration was associated with reduced lung function, whereas higher dietary niacin intake was associated with improved lung function. Notably, BCIPP levels showed positive associations between dietary niacin intake and FEV₁ [β (95% CI) = 0.11 (0.06, 0.16), p_adj < 0.001] and FVC [β (95% CI) = 0.09 (0.05, 0.13), p_adj < 0.001] in males with lower BCIPP exposure. In male mice, TCIPP exposure caused dose-dependent lung injury, inflammation, and oxidative stress, while niacin supplementation alleviated lung damage, improved lung function, and restored antioxidant defenses by inhibiting NF-κB phosphorylation. Niacin supplementation alleviated TCIPP-induced lung injury in males by inhibiting oxidative stress and NF-κB activation, suggesting niacin as a potential nutritional strategy to improve lung function.

Marfan syndrome (MFS) is a genetic disorder caused by mutations in the fibrillin-1 (Fbn1) gene, leading to structurally abnormal elastic fibers and diverse clinical manifestations. Aortic root dilation represents the most serious threat, often requiring prophylactic surgical repair. Emerging evidence suggests that MFS patients experience increased pain sensitivity, contributing to functional impairment and reduced quality of life. Here, we used C57BL/6 wild-type and Fbn1^C1041G/+ (MFS) mice to examine brain transcriptomics, aortic histology, nociceptive behaviors, grip strength, and spinal cord gene expression in both sexes at 2, 4, 6, 8, and 16 months of age. Transcriptomic analysis revealed reduced activation of pain-related pathways in young males and aged females, with a reversal in aged males, suggesting age- and sex-dependent differences in pain modulation. Behavioral testing showed progressive mechanical and thermal hypersensitivity in MFS mice, with cold allodynia as the earliest manifestation with late-onset muscle weakness. In the spinal cord of 16-month-old MFS mice, increased expression of key excitatory and nociceptive markers was observed, consistent with the pain hypersensitivity phenotype. In addition, aged female MFS mice exhibited elevated spinal expression of pro-inflammatory cytokines, inducible nitric oxide synthase, and Nox4, whereas males showed increased transforming growth factor-β1 and Nox1, reflecting distinct inflammatory and oxidative stress profiles. These findings demonstrate that Fbn1^C1041G/+ mice reproduce pain hypersensitivity and muscle deficits observed in MFS patients, supporting their use as a preclinical model. Our results suggest that enhanced spinal excitatory/nociceptive signaling, together with neuroinflammation and oxidative stress, contributes to sex- and age-specific pain mechanisms in MFS.

Potato is a globally important non-cereal crop in which infection with potato spindle tuber viroid (PSTVd) can cause stunted growth and significantly reduce tuber yield. We previously showed that PSTVd induces accumulation of the plant hormone jasmonic acid (JA) and alters antioxidant responses in potato plants. To clarify the role of JA in response to PSTVd, we analyzed disease development in transgenic JA-deficient opr3 and JA-insensitive coi1 lines compared to the wild-type. Transcriptomic analysis using RNA-Seq revealed that most genotype-specific differentially expressed genes (DEGs) in all comparisons were enriched in plant hormone signal transduction, plant-pathogen interaction, and MAPK signaling pathways, although the number of DEGs varied. These differences were confirmed by independent data from RT-qPCR, hormone, and hydrogen peroxide (H₂O₂) analyses. After PSTVd infection, opr3 plants showed enhanced JA signaling and increased abscisic acid (ABA) and auxin (AUX) content. In contrast, coi1 plants showed reduced ABA, AUX, and salicylic acid content. Both opr3 and coi1 plants showed reduced JA and H₂O₂ content and lower expression of defense-related genes, resulting in milder symptoms but increased viroid accumulation. In addition, treatment with methyl jasmonate alleviated symptoms in infected wild-type plants. Together, these results indicate a modulatory role for JA and JA signaling in basal immune responses and symptom development in the potato-PSTVd interaction.