BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by oxidative stress and impaired skin barrier function. These pathological features contribute to persistent inflammation and symptom exacerbation, highlighting the need for therapies that can both reduce oxidative stress and modulate inflammatory pathways. METHODS:Ulmus pumila Linné (Ulmi) was prepared via hot water extraction and tested for cytotoxicity, antioxidant activity, and anti-inflammatory effects in HaCaT keratinocytes stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). In vivo efficacy was assessed using a 2,4-dinitrochlorobenzene (DNCB)-induced AD model in SKH-1 hairless mice. Bioactive compounds were identified using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS), and molecular docking analysis was performed to evaluate the binding affinity of these compounds to aldehyde dehydrogenase 2 (ALDH2). RESULTS:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays confirmed that Ulmi was safe at concentrations up to 400 μg/mL. In TNF-α/IFN-γ-stimulated HaCaT cells, Ulmi significantly upregulated ALDH2 expression in a dose-dependent manner and reduced reactive oxygen species (ROS) production. The extract also suppressed pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), while inhibiting the activation of nuclear factor kappa B (NF-κB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. In the AD mouse model, Ulmi treatment improved clinical skin scores, reduced epidermal thickness, and decreased inflammatory markers compared to untreated controls. LC-QTOF-MS/MS analysis identified eight bioactive compounds, with procyanidin B2, catechin, and epicatechin as major constituents. Molecular docking revealed that procyanidin B2 had the strongest binding affinity to ALDH2 (-9.5 kcal/mol). CONCLUSIONS:These findings demonstrate that Ulmi effectively ameliorates AD-like symptoms through ALDH2-mediated antioxidant mechanisms and anti-inflammatory effects. The results suggest that Ulmi may serve as a promising natural therapeutic agent for the management of atopic dermatitis.
Aminochrome, an endogenous neurotoxin, has been implicated in the loss of neuromelanin-containing dopaminergic neurons in the nigrostriatal system in Parkinson's disease. Although aminochrome-induced oxidative stress and its inhibitory effects on microtubule polymerization are well documented, its impact on protein aggregation remains poorly understood. The aim of this research was to evaluate the effects of aminochrome on protein aggregate accumulation in SH-SY5Y cells differentiated into dopaminergic neurons. While the role of aminochrome in autophagy has been described, its direct effect on autophagosome-lysosome fusion has not been studied. Our findings reveal that aminochrome, like vinblastine, delays autophagosome-lysosome fusion and induces cell death. This inhibitory effect was also observed in the presence of autophagy inducers, which partially attenuated aminochrome-induced cell death. Under these conditions of disruptions in autophagosome-lysosome fusion, a marked accumulation of perinuclear vimentin and ubiquitin aggregates was observed. Aminochrome also increased colocalization between vimentin and ubiquitin. Interestingly, ubiquitin aggregates were also detected within the nucleus. These findings suggest that aminochrome-induced disruption of the microtubule network, particularly its impairment of autophagosome-lysosome fusion and promotion of protein aggregation, may represent a critical mechanism leading to cell death. In addition, inhibition of autophagosome-lysosome fusion may contribute to the accumulation of perinuclear and nuclear protein aggregates, which may be associated with either toxic or non-toxic pathways. Our findings underscore the therapeutic potential of targeting both microtubule stabilization and proteostasis pathways, including autophagy and the ubiquitin-proteasome system (UPS), in Parkinson's disease, highlighting the need for further research into nuclear proteotoxicity mechanisms.
Scorpion venom peptides, with their stable disulfide backbone, compact structural framework, and highly selective regulation of ion channels, have long been regarded as important molecular probes in neuropharmacology. However, recent studies have revealed their potential for regulating oxidative stress, inflammation, and neuroprotection, making them a new research frontier. In this article, we focus on scorpion venom peptides as drugs, constructing an integrated knowledge framework from structural classification to clinical translation. First, scorpion venom peptides are systematically classified based on cysteine arrangement patterns and three-dimensional folding topology, and their structure-activity relationships are summarized. Based on this, the molecular mechanisms by which scorpion venom peptides regulate ion channels are systematically analyzed. We review the emerging pharmacological activities of scorpion venom peptides. Of particular note, the representative molecule SVHRSP has shown multi-target synergistic antioxidant and neuroprotective activity in models of Parkinson's disease. We also systematically evaluate the application of engineering strategies, including cyclisation modification, nanodelivery, recombinant expression, and AI-assisted optimization, to overcome the translational bottlenecks in the development of scorpion venom peptides. However, it should be noted that most SVHRSP-related findings have been reported by a single research group; independent replication, pharmacokinetic characterization, and human efficacy data are still lacking. Its IND approval permits clinical investigation but does not yet constitute proven therapeutic benefit in patients. By integrating molecular structure, redox regulation mechanisms, and translational medicine perspectives, this review aims at providing a theoretical basis and practical pathways for scorpion venom peptides as precision therapeutic molecules for oxidative stress-related diseases.
Optimizing the extraction of bioactive compounds from Solidago sp. is essential for the development of plant-derived products with therapeutic and nutraceutical potential. Microwave-assisted (MW) and thermal maceration (TM) extraction of S. canadensis aerial parts were comparatively investigated to maximize total flavonoid content (TFC). The obtained extracts were subsequently freeze-dried for storage prior to chemical and biological analyses. Extraction conditions were optimized using a Box-Behnken design. Chemical characterization was performed by FTIR, HPLC-PDA, LC-MS/MS, and GC-MS, enabling detailed profiling of phenolic compounds and terpenoids. Antioxidant capacity was assessed using the DPPH radical scavenging assay, while cytotoxic activity was evaluated against HepG2, HCT-8, and HT-29 tumor cell lines, with HEK-293 cells used as a non-tumorigenic control cell line. Multivariate analysis (PCA) was applied to establish relationships between phytochemical composition and biological responses. Higher TFC values were obtained using MW extraction, whereas TM extracts exhibited greater antioxidant activity. Both extract types induced selective cytotoxic effects against tumor cell lines, while maintaining negligible toxicity toward normal HEK-293 cells. PCA revealed distinct clustering patterns between MW and TM extracts and confirmed a strong association between phenolic composition and bioactivity. The combination of optimized extraction, freeze-drying, and integrated chemical-biological evaluation produced S. canadensis extracts with well-defined phytochemical profiles and biological activity, supporting their potential use in nutraceutical, and pharmaceutical applications.
Despite increasing efforts to improve cardiovascular disease (CVD) risk evaluation and management, it remains a leading cause of mortality and morbidity worldwide. This has driven interest in high-density lipoprotein (HDL)-related biomarkers as indicators of oxidative stress and atherogenic processes not fully captured by traditional lipid measurements. In this study, we examined specific paraoxonase 1 (PON1) activity and its relationship with anthropometric, blood pressure, and lipid metabolism measures in 100 middle-aged Lithuanian individuals at high cardiovascular risk. HDL fractions were isolated using iodixanol-based density gradient centrifugation. PON1 concentration and arylesterase activity were measured, and specific activity was defined as arylesterase activity normalized to PON1 concentration. No significant associations were observed between specific PON1 activity and age, body mass index, waist circumference, blood pressure, smoking status, or statin use. Specific PON1 activity was independently associated with lower risk-weighted apolipoprotein B and lower low-density lipoprotein cholesterol levels. These exploratory findings suggest that higher specific PON1 activity may reflect a less atherogenic lipid profile in individuals at high cardiovascular risk, as indicated by its association with LDL-C and with risk-weighted apolipoprotein B. Because direct oxidative stress and inflammatory markers were not measured, interpretations regarding oxidative burden should be considered indirect and hypothesis-generating. Given the cross-sectional nature of the study and the relatively small sample size, these results should be interpreted as exploratory and hypothesis-generating. Further longitudinal studies in larger populations are needed to confirm these observations.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent multisystem disorder and is strongly associated with increased cardiovascular risk. Cardiovascular diseases represent the leading cause of mortality in this population. As the hepatic manifestation of systemic metabolic dysfunction, MASLD is initiated by excess lipid accumulation driven by increased dietary fatty acid intake and accelerated de novo lipogenesis. This triglyceride overload induces lipotoxicity, triggering hepatocellular injury, immune activation, and mitochondrial dysfunction. Excessive mitochondrial reactive oxygen species (ROS) generation acts as a critical second hit, promoting inflammatory cytokine production and disease progression. Beyond lipid dysregulation, impaired hepatic insulin signaling leads to hyperglycemia and compensatory hyperinsulinemia, further stimulating lipogenesis and reinforcing a self-perpetuating metabolic cycle. Persistent ROS production overwhelms antioxidant defenses and depletes hepatic glutathione (GSH), resulting in systemic redox imbalance. These disturbances extend beyond the liver, contributing to atherogenic dyslipidemia and chronic inflammation. In parallel, gut dysbiosis and increased intestinal permeability amplify immune activation. Reduced circulating GSH further weakens systemic antioxidant capacity; oxidative stress may represent a central mechanistic link between MASLD and CVD. In concert with metabolic and inflammatory mediators, ROS disrupt pathways governing vascular and myocardial homeostasis, leading to coronary atherosclerosis, microvascular dysfunction, left ventricular remodeling, hypertrophy, and impaired relaxation. Clinically, this translates into an increased burden of coronary artery disease and heart failure, particularly heart failure with preserved ejection fraction. Given this integrated pathophysiology, early identification of subclinical cardiovascular involvement is essential. We highlight emerging biomarkers, advocate for multidisciplinary screening strategies, and discuss integrated pharmacological approaches targeting shared metabolic pathways. Recognizing MASLD as a cardiovascular risk amplifier is critical for improving risk stratification and enabling the development of effective, co-targeted therapeutic strategies.
Iron is essential for life, but its safe use by the body depends on it being kept within tightly controlled compartments. When this compartmentalisation is disrupted-through haemolysis, saturation of scavenger proteins, or dysregulation of the hepcidin-ferroportin axis-damaging iron species accumulate in the circulation and within vascular cells, with potentially serious consequences for endothelial function. This review explores the mechanisms by which iron dysregulation compromises vascular endothelial cell biology across a range of disease states, including haemolytic anaemias, atherosclerosis, cerebrovascular disease, extracorporeal circulatory support, and iatrogenic iron loading. Common pathological themes emerge: depletion of nitric oxide bioavailability, oxidative stress, endothelial activation, and in chronic settings, vascular remodelling. The review subsequently focuses in depth on the pulmonary vasculature, where dysregulated iron compartmentalisation has emerged as a key contributor to the pathogenesis of pulmonary hypertension. Here, iron-driven mitochondrial dysfunction, smooth muscle cell proliferation, and iron-dependent lipid peroxidation via ferroptosis are discussed as mechanistic drivers of pulmonary vascular remodelling. The therapeutic implications of targeting iron handling in pulmonary hypertension are considered, including modulation of the hepcidin-ferroportin axis. Together, the evidence presented highlights disordered iron compartmentalisation as a unifying pathological thread across vascular disease and a compelling target for intervention.
Cryopreservation of gametes is crucial for conserving genetic diversity in livestock and endangered species, but the process can significantly impair sperm quality due to oxidative stress. Our aim was to evaluate the impacts of coenzyme Q10 (CoQ10) supplementation on the in vitro quality of cooled and cryopreserved goat semen. Semen samples collected from six mature Saanen bucks were pooled then diluted with AndroMed® semen extender to a final concentration of 800 × 106 sperm/mL. Diluted semen was supplemented with 0, 1, 2, 5, 10, and 20 µM CoQ10. Extended semen was either cooled at 4 °C for 72 h or cryopreserved using a Styrofoam box in which the straws were arranged on the freezing rack and placed 4 cm over the liquid nitrogen (LN2) for 10 min then stored in a LN2 tank for one-week before being thawed at 37 °C for 30 sec. Sperm quality, including total and progressive motility, sperm kinematics, live sperm %, and sperm membrane integrity, was assessed at 0 h (fresh semen), and 24, 48, and 72 h post-cooling. For post-thaw sperm, we evaluated the same parameters plus acrosome integrity, mitochondrial activity, lipid peroxidation, and sperm ultrastructural changes using scanning electron microscopy (SEM). The pooled semen sample was considered the experimental unit for all treatments. Cooled semen data were analyzed using a General Linear Model (GLM) with univariate analysis, followed by Tukey's test for multiple comparisons. In contrast, data from frozen-thawed semen were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's test. CoQ10 supplementation at 10 and 20 µM significantly (p < 0.05) improved sperm motility, viability, and membrane integrity in cooled and frozen-thawed semen in comparison with the control group (0 µM CoQ10). Moreover, the same concentrations significantly (p < 0.05) enhanced acrosome integrity, mitochondrial activity, and reduced the percentages of sperm with lipid peroxidation in frozen-thawed semen. Furthermore, 10 and 20 µM CoQ10 significantly mitigated the ultrastructural defects in frozen-thawed spermatozoa. In conclusion, CoQ10 supplementation during the cooling and cryopreservation of dairy goat semen significantly improved sperm quality. Among the tested concentrations, 10 and 20 µM exhibited the most favorable outcomes.
Myocardial infarction (MI) remains the leading cause of death globally. Current treatment strategies involve restoring blood flow to the coronary artery, but have shortcomings in that these procedures cannot reverse damage to the myocardium that has already occurred. Therefore, therapies that can decrease the severity of ischemic damage are needed. Oxidative stress is an early and major driver of cardiomyocyte death following MI. Rhynchophylline (RHY) is a natural alkaloid known for its antioxidant activity; however, whether it can protect against MI-induced ischemic injury, as well as its underlying mechanism of action, remains unexplored. We performed murine models of surgical MI and examined the effects and mechanisms of RHY in protecting against myocardial ischemic injury. A sirtuin 1 (SIRT1)-specific inhibitor, EX-527, was subsequently used to verify that the cardioprotective effects of RHY were dependent upon targeted SIRT1-activation. Mice administered with RHY significantly protected against ischemic injury following MI, with improved cardiac function, reduced infarct size, and decreased levels of oxidative and DNA damage. The cardioprotective effect of RHY is associated with activation of the SIRT1 and its downstream redox-sensitive transcription factors: nuclear factor erythroid 2-related factor 2 (NRF2) and forkhead-box protein O3 (FOXO3a). The cardioprotective and antioxidant effects of RHY were abolished by EX-527, a selective SIRT1 inhibitor. Our findings provide evidence for the robust antioxidant properties of RHY in protecting against MI injury via activating the SIRT1/NRF2/FOXO3a signaling axis. These findings provide new mechanistic insight into the preconditioning-like cardioprotective potential of RHY during myocardial infarction.
The exact mechanisms of skin involvement in type 1 diabetes (DM1) remain poorly understood. This study aimed to evaluate the relationship between antioxidants, oxidative stress, protein glycation, and glycoxidation, as well as matrix metalloproteinase (MMP) activity, in the skin of rats with DM1, while investigating whether insulin administration improves skin homeostasis. Male Wistar rats were assigned to three groups: control, diabetes, and diabetes treated with insulin. Significantly higher expression of GSH (gluthatione) and GSH-Px (glutathione peroxidase), elevated levels of AGE (Advanced Glycation End products), DT (dityrosine), KN (kynurenine), NFKN (N-formylkynurenine) and ONOO- (peroxynitrite), as well as increased activity of GLU (β-D-glucuronidase), NADPH oxidase (NOX) and MMP-1, -2, -3, -7, -9, -11 and -13 were observed in the skin of rats with DM1. Insulin treatment normalizes the skin's antioxidant barrier and eliminates oxidative stress. It also reduces the intensity of protein glycation and glycoxidation, though not to the levels observed in the control group. Summarizing, in diabetic skin there is a complex interaction between the thiol antioxidant barrier, oxidative damage, protein glycation and glycoxidation as well as MMP expression. Insulin restores physiological balance in skin cells; however, glycation and ECM remodeling are still more pronounced than in healthy skin.
Natural pigment lycopene (LYC), a carotenoid, possesses antioxidant, anti-apoptotic, anticancer, and immunoenhancing properties. During in vitro culture, this substance protects oocytes and early embryos from damage caused by reactive oxygen species (ROS), thereby enhancing the in vitro maturation (IVM) rate of oocytes and the developmental competence of early embryos. This study aimed to investigate the effects of supplementing different concentrations of LYC (0, 5, 10, and 15 μM) during in vitro culture of sheep oocytes and early embryos on their developmental competence. In contrast to the control group, the 5 μM LYC treatment group displayed a marked increase in the first polar body extrusion rate and the extent of cumulus cell expansion, as well as a significantly higher proportion of normal spindle assembly in sheep oocytes, but 15 μM LYC appeared to negatively affect oocyte maturation. Relative to all other experimental groups, the 5 μM LYC treatment group displayed significantly elevated rates of cleavage and blastocyst rate during early in vitro embryonic development. The levels of ROS in mature oocytes and early embryos were significantly decreased, whereas the GSH level was significantly elevated. Furthermore, LYC treatment significantly enhanced mitochondrial activity and markedly elevated the mitochondrial membrane potential (MMP) in mature oocytes and early embryos. Moreover, the total cell number of blastocysts was significantly increased. Moreover, in early embryos, the transcript levels of genes associated with both oxidative stress and apoptosis were favorably regulated. In conclusion, LYC supplementation boosted the rates of oocyte maturation and blastocyst formation in sheep, while elevating the developmental capacity of early embryos.
Heart failure (HF) remains a major cause of morbidity and mortality despite substantial therapeutic progress, and important phenotype-specific treatment gaps persist. Protein S-nitrosylation (SNO) is a reversible cysteine-centered post-translational modification (PTM) whose reported associations with selected HF-relevant contexts, including vascular-endothelial dysfunction, mitochondrial-energetic remodeling, Ca2+-handling abnormalities, and selected receptor- or stress-related signaling observations, are supported to varying degrees. In this review, we evaluate reported mechanisms that may regulate cardiac SNO and define the evidentiary boundaries that constrain interpretation across HF-relevant settings. Available studies suggest that altered SNO homeostasis is associated with selected HF-related processes, but the strength of support varies substantially across targets, phenotypes, and disease contexts. Many mechanistic observations derive from animal models, cultured systems, donor-based perturbations, or non-HF settings. These should, therefore, be interpreted as hypothesis-generating rather than as established mechanisms in human HF. We accordingly distinguish findings supported by human HF tissue or HF-relevant in vivo evidence from more preliminary observations and highlight the need for human, site-resolved, and, where feasible, quantitatively grounded datasets. Future studies should prioritize stronger tissue anchoring, better integration of circulating and myocardial readouts, and closer alignment between mechanistic claims and the strength of the supporting evidence.
Statins are commonly used cholesterol-lowering drugs, but their effects on astrocyte oxidative metabolism are poorly understood. To investigate this, rat astrocytes were exposed to 200 nM atorvastatin or simvastatin for 6 days and then assessed for changes in coenzyme Q (CoQ) homeostasis, mitochondrial function, and energy metabolism. Both statins comparably decreased cellular CoQ9 and CoQ10 levels (~35%), with greater losses of their reduced antioxidant forms (60-75%). Lower intracellular and mitochondrial levels of reactive oxygen species (ROS) were accompanied by the upregulation of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant pathways (superoxide dismutase 1 and glutathione reductase) and metabolic stress response factors, including hypoxia-inducible factor 1-alpha (HIF1α) and brain-derived neurotrophic factor (BDNF). Both statins promoted glycolytic reprogramming, mitochondrial fission, and biogenesis while impairing oxidative phosphorylation, as evidenced by reduced ATP-linked respiration, increased proton leak, and lower ATP levels. These findings suggest that statin-treated astrocytes adapt by prioritizing redox homeostasis over ATP production. CoQ10 supplementation increased cellular CoQ10 levels and restored ATP levels without further decreasing ROS, suggesting that its primary benefit is bioenergetic support, not additional antioxidant protection. Overall, statin-induced CoQ deficiency induces adaptive metabolic remodeling of astrocytes, while CoQ10 supplementation may help maintain energy metabolism under these conditions.
Daidzein is a naturally occurring isoflavone phytoestrogen, mainly found in leguminous plants. This component exerts anti-inflammatory effects by regulating inflammatory cells via multiple targets, blocking core inflammatory pathways, and inhibiting the release of inflammatory factors. It also scavenges reactive oxygen species, activates the antioxidant enzyme system, and regulates antioxidant signaling pathways to achieve antioxidant effects. By regulating these two core pathological processes, it exerts protective effects in diseases such as cancer, cardiovascular disease, and acute kidney injury, based on preclinical evidence. The development of nanodelivery systems has effectively improved the physicochemical properties of daidzein, enhanced its bioavailability, and enabled disease-targeted delivery. Most previous reviews have either focused exclusively on daidzein or broadly covered the pharmacological activities of isoflavones, yet have largely overlooked the dual anti-inflammatory and antioxidant mechanisms specific to daidzein. This review summarizes these mechanisms and their preclinical effects on various diseases, including cancer, cardiovascular diseases, and acute kidney injury. It also reviews the pharmacokinetic limitations of daidzein and recent progress in nanodelivery strategies aimed at enhancing its bioavailability and bioactivity. Overall, this review serves as a reference for the future standardized comparison of nanocarriers, targeted therapies, and clinical applications.
Hypoxia-induced radioresistance remains a major obstacle in non-small cell lung cancer (NSCLC) radiotherapy. This study investigates whether artificially activating mitochondrial reverse electron transfer (RET) can enhance radiosensitivity in NSCLC by triggering oxidative stress. An in vitro hypoxia/reoxygenation (H/R) model was established in A549 cells to assess reactive oxygen species (ROS) levels, mitochondrial function, and metabolic alterations using fluorescence probes, flow cytometry, confocal microscopy, and targeted metabolomics. Mitochondrial complex inhibitors and dimethyl succinate (DM-S) were employed to validate the RET mechanism, and radiosensitivity was evaluated through clonogenic survival, apoptosis assays, and γ-H2AX staining. In vivo, A549 tumor-bearing mice received high oxygen (95% O2) combined with DM-S and localized irradiation (4 Gy); tumor growth, histopathology, and immunohistochemistry were examined. H/R triggered substantial mitochondrial ROS production via complex I-mediated RET, dependent on a high mitochondrial membrane potential and electron transport chain imbalance, with succinate accumulation serving as a key metabolic switch. Exogenous DM-S exacerbated H/R-induced oxidative damage, DNA fragmentation (8-OHdG elevation, mtDNA integrity loss), and mitochondrial network disruption. H/R combined with DM-S significantly enhanced in vitro radiosensitivity, reducing clonogenic survival and increasing apoptosis to 53.4% ± 1.9% versus 10.3% ± 1.2% with irradiation alone. In vivo, the combination therapy markedly suppressed tumor growth, induced apoptosis and oxidative lipid damage (4-HNE), alleviated hypoxia (reduced HIF-1α), and showed no overt toxicity. These findings demonstrate that activating mitochondrial RET effectively enhances radiosensitivity in NSCLC. Succinate metabolism is a critical therapeutic target, and combining high oxygen with a succinate analog represents a promising radiosensitization strategy for hypoxic tumors.
Aristotelia chilensis (maqui berry) is a Chilean native fruit rich in anthocyanins with potential antioxidant, glycemic, cardiometabolic, and ocular benefits, but its clinical efficacy remains unclear. This systematic review synthesized and critically appraised human trials evaluating oral maqui supplementation in adults. Following PRISMA 2020 and a PROSPERO-registered protocol, five databases were searched, and risk of bias and certainty of evidence were assessed using RoB 2/ROBINS-I and GRADE. Twelve clinical trials published between 2014 and 2023 were included. Acute studies consistently showed reduced postprandial glucose and modulation of insulin response, whereas chronic interventions showed modest and inconsistent effects on HbA1c, lipid profile, and other cardiometabolic markers. Favorable changes were also reported for oxidative stress biomarkers and autonomic parameters, although these findings were mainly based on surrogate endpoints. The most consistent evidence was observed in the ocular domain, where maqui supplementation improved tear production, dry eye symptoms, and tear inflammatory markers. The overall certainty of evidence ranged from moderate to very low because of methodological heterogeneity, small sample sizes, and short intervention duration. Maqui berry supplementation shows promise, particularly for acute glycemic control and ocular surface health, but larger long-term randomized trials using standardized formulations are needed before definitive clinical recommendations can be made.
Oxidative stress and inflammation play a key role in many diseases. This study evaluated the potential of bioactive compounds from Red-belted Bracket and Artist’s Bracket mushrooms to mitigate these processes. Multistep extraction yielded fractions with diversified composition (triterpenoids, polysaccharides) and bioactivities, including antioxidant properties and inhibition of pro-inflammatory enzymes. Both species were rich in triterpenoids: ethanolic extracts from Artist’s Bracket contained mainly ganoderenic and ganoderic acids (≈31 μg/g d.w.), while Red-belted Bracket extracts contained phenolic acids (≈20 μg/g d.w., mainly vanillic and chebulic acids) and triterpenoids (≈73 μg/g d.w., mainly forpinic and formipinic acids). The alkaline and ethanolic extracts exhibited the highest radical scavenging and reducing activities. Lipoxygenase was inhibited only by ethanolic extracts, with IC50 values of 0.93 mg d.w./mL for Artist’s Bracket (mixed inhibition) and 0.62 mg d.w./mL for Red-belted Bracket (noncompetitive). Artist’s Bracket was also a potent source of xanthine oxidase inhibitors acting uncompetitively (IC50 = 0.71, 1.39, and 2.06 mg d.w./mL for ethanolic, methanolic, and aqueous extracts, respectively). In contrast, Red-belted Bracket was less active (IC50 = 3.84 mg d.w./mL, noncompetitive). In conclusion, these mushrooms, particularly their ethanolic extracts, are promising sources of compounds with antioxidant and anti-inflammatory activities, acting as effective inhibitors of lipoxygenase and xanthine oxidase.
Mitochondrial electron transport chain (ETC) dysfunction is a major driver of bioenergetic failure, redox imbalance, and drug toxicity, yet strategies to restore oxidative phosphorylation under ETC blockade remain limited. Redox-active small molecules could, in principle, shuttle electrons from NADH to distal ETC components and oxygen, thereby modulating both respiration and reactive oxygen species (ROS) formation. Here, we show that the enzyme-independent redox cycler phenazine methosulfate (PMS) rewires mitochondrial redox circuits and restores respiration in human glioblastoma cells and cell-free systems under ETC inhibition. At subtoxic concentrations, PMS acutely increased oxygen consumption and mitochondrial superoxide generation via NADH-PMS-O2 redox cycling, while restoring mitochondrial membrane potential and ATP synthesis under ETC blockade, and shifting metabolism away from glycolytic lactate production. This profile is consistent with a protective redox-bypass role, distinct from the pro-apoptotic effects reported following high-dose, prolonged PMS exposure. The PMS-driven restoration of electron flow, mitochondrial membrane potential, and respiratory ATP synthesis under inhibition of Complex I (rotenone), III (antimycin A and myxothiazol), and/or IV (cyanide) is consistent with direct cytochrome c reduction, as demonstrated herein, and engagement of multiple ETC redox centers, including coenzyme Q10. In metformin-treated cells, PMS reversed suppression of respiration and lactate accumulation, outperforming existing redox-bypass strategies. These findings identify PMS-driven redox cycling as a previously unrecognized chemical redox-bypass mechanism that both regenerates mitochondrial bioenergetics and reshapes ROS production, suggesting a potential approach to counteract drug- and toxin-induced mitochondrial dysfunction and to exploit redox vulnerabilities in cancer.
The present study investigated the use of natural deep eutectic solvents (NaDESs) combined with ultrasound-assisted extraction (UAE) for the efficient recovery of anthocyanins and antioxidant phenolics from Damask rose (DR). A wide range of environmentally friendly solvents was screened, and choline chloride-propylene glycol (ChCl-PG) was identified as the most effective extraction medium. The extraction conditions were optimized using response surface methodology (RSM) and artificial neural network (ANN) models to maximize anthocyanin and phenolic contents, as well as antioxidant activity. Under the optimal parameters, the DR extracts exhibited relatively high levels of bioactive compounds, including total anthocyanin content of 5.2-5.3 mg cyanidin-3-glucoside equivalents g-1 sample, total phenolic content of 63.4-64.2 mg gallic acid equivalents g-1 sample, along with substantial antioxidant potential (DPPH: 68.2-68.8% inhibition, FRAP: 581.6-591.9 μmol Trolox equivalents g-1 sample). Chromatographic analysis of the optimum extract revealed cyanidin as the predominant anthocyanidin in DR, and its stability was further evaluated, revealing improved preservation under dark conditions at lower temperatures over a 15-day storage period. Moreover, the IC50 values confirmed antimicrobial effects against the tested foodborne pathogens. Furthermore, the inhibitory effect of the DR extract remained stable against S. aureus and S. cerevisiae throughout the storage period. Overall, the findings demonstrate that NaDES-UAE is a promising and sustainable approach for obtaining anthocyanin-rich DR extracts with antioxidant and antimicrobial potential.
