Antioxidants最新文献

Although interferon-gamma (IFN-γ) is known as a critical factor in polarizing macrophages into the pro-inflammatory state for immune response, how dietary flavonoids regulate IFN-γ response for anti-inflammation is incompletely elucidated. This study aims to investigate the effect of fisetin, a typical flavonol, on the inhibition of IFN-γ-induced inflammation by RNA sequencing (RNA-Seq) and cellular metabolism analysis. RAW264 macrophages pretreated with fisetin following IFN-γ stimulation were subjected to RNA-Seq to analyze alterations in gene expression. Cellular signaling and transcription were investigated using enrichment analysis, motif analysis, and transcription factor prediction. Cellular metabolic state was assessed by measuring the oxygen consumption rate (OCR) and lactate level to reflect mitochondrial respiration and glycolysis. Alterations in signaling proteins were confirmed by Western blot. The results revealed that fisetin downregulated the IFN-γ-induced expression of pro-inflammatory genes and M1 marker genes such as Cxcl9, Il6, Cd80, Cd86, and Nos2. In cellular metabolism, fisetin upregulated the oxidative phosphorylation (OXPHOS) pathway, restored impaired OCR, and reduced lactate production induced by IFN-γ. Motif analysis suggested that fisetin suppressed the activation of IFN-regulatory factor 1 (IRF1). Western blot data further confirmed that fisetin inhibited the phosphorylation of Jak1, Jak2, and STAT1, and decreased the nuclear accumulation of phosphorylated STAT1 and IRF1 induced by IFN-γ. Taken together, our data revealed that fisetin is a potent flavonoid that attenuates IFN-γ-stimulated murine macrophage inflammation and ameliorates disrupted cellular metabolism with a possible Jak1/2-STAT1-IRF1 pathway.

The interest in new sources of bioactive compounds has been driven by the search for natural antioxidants capable of attenuating the toxicity of reactive oxygen species, as well as the emergence of pathogens resistant to antimicrobials. In this sense, we explored the potential of the macaúba epicarp. Compounds such as piceatannol, 3,4,5,3',5'-penta-hydroxy-trans-stilbene (PHS), and in lower amounts, resveratrol were identified in extracts through techniques such as medium-pressure liquid chromatography, HPLC-MS, and imaging mass spectrometry (IMS), which confirmed the exclusive localization of PHS and piceatannol in the outer epicarp. Extraction with aqueous acetone (Me₂CO:H₂O) and its EtOAC fraction showed the highest yields of stilbenes and, moreover, it efficiently increased the tolerance of Saccharomyces cerevisiae to oxidative stress. Additionally, the Me₂CO:H₂O extract presented antibacterial and anti-cryptococcal activity, with piceatannol and resveratrol increasing survival rates of Galleria mellonella subjected to fungal infection. In silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis indicates low toxicity for piceatannol, PHS, and resveratrol, in addition to pharmacokinetic parameters that allow their use. These findings indicate the use of macaúba epicarp as a source of bioactive compounds valuable for the food, cosmetic, and pharmaceutical industries.

B-lymphocyte-induced maturation protein 1 (Blimp-1) is a transcription factor that, among other functions, modulates metabolism and helps to regulate antioxidant pathways, which is important in the context of chronic inflammatory diseases like diabetes, cardiovascular disease, and autoimmune disease. In immune cell function, Blimp-1 has a modulatory role in the orchestration of metabolic reprogramming and as a promoter of anti-inflammatory cytokines, including IL-10, responsible for modulating oxidative stress and immune homeostasis. Moreover, Blimp-1 also modulates key metabolic aspects, such as glycolysis and fatty acid oxidation, which regulate reactive oxygen species levels, as well as tissue protection. This review depicts Blimp-1 as an important regulator of antioxidant defenses and anti-inflammation and suggests that the protein could serve as a therapeutic target in chronic inflammatory and metabolic dysregulation conditions. The modulation of Blimp-1 in diseases such as diabetic coronary heart disease and atherosclerosis could alleviate oxidative stress, augment the protection of tissues, and improve disease outcomes. The therapeutic potential for the development of new treatments for these chronic conditions lies in the synergy between the regulation of Blimp-1 and antioxidant therapies, which are future directions that may be pursued. This review emphasizes Blimp-1's emerging importance as a novel regulator in the pathogenesis of inflammatory diseases, providing new opportunities for therapeutic intervention.

Concerns have arisen about the impact of wireless technology on male fertility, particularly regarding the duration of 2.45 GHz Wi-Fi radiation exposure. This study examines the influence of various exposure durations on sperm parameters and testicular histopathology, focusing on malondialdehyde as an oxidative stress marker. Twenty-four Sprague Dawley rats were exposed for eight weeks, after which their sperm concentration, motility, and viability and testicular histopathology were assessed. Malondialdehyde levels were measured using an Enzyme-Linked Immunosorbent Assay. One-way ANOVAs with Tukey's post hoc tests were conducted for the sperm concentration, motility, and viability; the seminiferous epithelium height; and malondialdehyde. The Kruskal-Wallis H test was used for the Johnsen Score and seminiferous tubule diameter. The results indicated that 4 h of exposure to 2.45 GHz radiation induced oxidative stress and adversely affected sperm parameters and the testicular ultrastructure. Gradual recovery was observed at 8 h, with further improvement at 24 h, suggesting the activation of cell repair mechanisms. This was supported by significant changes in testicular organ coefficients, indicating potential recovery. Our findings suggest that Wi-Fi exposure reduces sperm fertility potential, with the body showing limited capacity for complete recovery from the damage.

The retinal pigment epithelium (RPE) is a highly specialised monolayer epithelium subjected to constant oxidative stress, which, in the long term, favours the development of a complex pathological process that is the underlying cause of macular damage. Therefore, counteracting the overproduction of ROS is the best-researched approach to preserve the functional integrity of the RPE. S-Petasin, a secondary metabolite extracted from the plant Petasites hybridus, has numerous biological effects, which highlight its anti-inflammatory and antioxidative properties. The aim of our study is to investigate whether S-Petasin exerts cytoprotective effects by protecting the RPE from oxidative damage. The effects of pretreatment with S-Petasin were assessed by the determination of the cell viability, intracellular ROS levels, activation of the Nrf2 pathway and the resulting post-transcriptional antioxidant/antiapoptotic response. Our results show that S-Petasin pretreatment (1) reduces intracellular ROS levels, improving cell viability of RPE exposed to oxidative damage; (2) activates the Nrf2 signalling pathway, modulating the post-transcriptional response of its antioxidant chemical biomarkers; (3) reduces the Bax levels, and an increase in those of Bcl-2, with a concomitant downregulation of the Bax/Bc-2 ratio. Overall, our results provide the first evidence that S-Petasin is able to protect the RPE from oxidative damage.

A variety of molecular and cellular changes distinguish the multifaceted biological process of aging. Recent studies in this decade have demonstrated the essential role of extracellular vesicles (EVs) in the aging process. Mitochondrial malfunction and increased oxidative stress are major contributors for the aging process. This review investigates the role of EVs in intercellular communication, tissue regeneration, and inflammation in the context of aging. We also discuss the exosome and its utility to reduce oxidative stress, which is a key part of aging, as well as the possibility of using the exosomes (EVs) as anti-aging drugs. Changes in cargo composition can influence the aging phenotype and impact the functionality of cells and tissues. Additionally, the role of EVs in oxidative stress during the aging process addresses potential treatment strategies and the development of biomarkers for age-associated disorders. The review also highlighted the role of exosomes in providing antioxidant properties, which help reduce excessive reactive oxygen species (ROS) and strengthen cellular defenses against oxidative stress. Additionally, it emphasized the role of extracellular vesicles (EVs) in age-related pathologies, such as neurodegenerative diseases, cardiovascular disorders, and immunosenescence, offering insights into targeted interventions for promoting healthy aging. This article provides a comprehensive analysis of the current body of knowledge regarding the therapeutic effects of EVs on aging, with a particular emphasis on the implications of this emerging field of research and its relationship to oxidative stress.

Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular disease (CVD) due to the accumulation of uremic toxins, altered redox state, and chronic systemic inflammation. This study aimed to analyze the relationship between the redox status of patients with CKD and the phenotype of microvesicles (MVs) subtypes, and cardiovascular events. The oxidative stress level of each participant was determined using an individualized OXY-SCORE. The relationship between pro-oxidant and antioxidant parameters and the expression of membrane markers in endothelial-derived microvesicles (EMVs) and platelet-derived microvesicles (PMVs) was established. Patients with advanced CKD (ACKD) and hemodialysis (HD) had a higher OXY-SCORE than healthy subjects (HS), whereas peritoneal dialysis (PD) patients had similar scores to HS. PD patients showed elevated PMVs and CD41 expression, whereas HD patients had higher EMVs and CD31 expression. Patients with ACKD had higher tissue factor (TF) expression in the PMVs and EMVs. TF expression was correlated with xanthine oxidase (XO) activity and was negatively correlated with antioxidant parameters. Patients with cardiovascular events show elevated TF. In conclusion, microvesicles and oxidative stress may serve as markers of cardiovascular risk in CKD, with TF expression in PMVs and EMVs being potential predictive and prognostic biomarkers of CVD.

Obesity and type 2 diabetes (T2D) increase cardiovascular risk, largely due to altered metabolic state. An early consequence of T2D/obesity is the loss of endothelial function and impaired nitric oxide (NO) signaling. In blood vessels, endothelial nitric oxide synthase (eNOS) synthesizes NO to maintain vessel homeostasis. The biological actions of NO are compromised by superoxide that is generated by NADPH oxidases (NOXs). Herein we investigated how altered metabolism affects superoxide/NO balance in obesity. We found that eNOS expression and NO bioavailability are significantly decreased in endothelial cells (ECs) from T2D patients and animal models of obesity. In parallel, PFKFB3, a key glycolytic regulatory enzyme, is significantly increased in ECs of obese animals. EC overexpression of wild-type and a cytosol-restricted mutant PFKFB3 decreased NO production due to increased eNOS-T495 phosphorylation. PFKFB3 also blunted Akt-S473 phosphorylation, reducing stimulus-dependent phosphorylation of S1177 and the activation of eNOS. Furthermore, PFKFB3 enhanced the activities of NOX1 and NOX5, which are major contributors to endothelial dysfunction. Prolonged exposure of ECs to high glucose or TNFα, which are hallmarks of T2D, leads to increased PFKFB3 expression. These results demonstrate a novel functional relationship between endothelial metabolism, ROS, and NO balance that may contribute to endothelial dysfunction in obesity.

This study aimed to isolate lactic acid bacteria (LAB) with strong antioxidant activity and potential probiotic properties from yak milk and dairy products in the Qinghai-Tibet Plateau. Initial screening of the isolates was performed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and a hydrogen peroxide tolerance test. Subsequently, the antioxidant capacity of the isolates was assessed through five distinct assays: 2,2'-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radical scavenging ability, superoxide anion radical scavenging ability, hydroxyl radical scavenging ability, a DPPH scavenging assay, and a reducing activity assay. The strains with the stronger antioxidant potential were then further evaluated for their probiotic properties. Whole-genome sequencing was conducted on Lactobacillus plantarum QL01. Among 1205 isolates, 9 strains exhibited potential antioxidant capabilities. Following probiotic property evaluation, QL01 was identified as a safe candidate due to its strong growth, strong adhesion ability, and resilience to acidic, bile, and simulated gastrointestinal conditions. Genome analysis revealed that most of QL01's genes were involved in carbohydrate metabolism. Further examination of antibiotic resistance and virulence factors confirmed its safety, meanwhile genes linked to adhesion and stress responses underscored its probiotic potential. In conclusion, QL01, a strong antioxidant strain, was successfully isolated, and its probiotic potential was confirmed through comprehensive in vitro and genomic analyses.

Metabolic dysfunction associated with steatotic liver disease (MASLD) is the result of disturbed lipid metabolism. In MASLD, the accumulation of free fatty acids (FFAs) in hepatocytes causes lipotoxicity mediated by oxidative stress. Coffee compounds are known for their beneficial effects in MASLD; however, the mechanisms still need to be further explored. The aim of this study was to elucidate the protective mechanisms of coffee compounds against palmitate-induced lipotoxicity in primary hepatocytes.

Methods: Primary hepatocytes were isolated from male Wistar rats and treated with palmitate (1 mmol/L) in combination with caffeine (CF: 1 mmol/L) or chlorogenic acid (CGA: 5 µmol/L). Mitochondrial ROS production, palmitate-induced necrosis, antioxidant response, ER stress markers and lipid droplet (LD) formation were assessed. Monoacylglycerols 2-SG (2-Stearolylglycerol), 2-OG (2-Oleoylglycerol) and SCD-1 (Stearoyl-CoA Desaturase 1) inhibitors were used to modulate LD formation. LD formation in steatotic Zucker rat hepatocytes was also investigated.

Results: CF and CGA prevented palmitate-induced cell death and reduced ROS production. CF and CGA induced the antioxidant response, especially HO-1 expression, but had no significant effect on ER stress markers. CF and CGA increased LD formation in palmitate-treated cells. This effect was significantly reduced by 2-SG and SCD-1 inhibitors but enhanced by 2-OG. Lipid droplets were associated with lower palmitate toxicity and reduced ROS production.

Conclusions: CF and CGA protect hepatocytes from lipotoxicity via modulation of the antioxidant response and enhance lipid droplet formation via an SCD-1-dependent mechanism. Oxidative stress-related toxicity in hepatocytes can be prevented by enhancing LD formation.