Redox Balance Research Articles

Prooxidant state in anticancer drugs and prospect use of mitochondrial cofactors and anti-inflammatory agents in cancer prevention.

An extensive body of literature has associated cancer with redox imbalance and inflammatory conditions. Thus, several studies and current clinical practice have relied on the use of anticancer drugs known to be associated with prooxidant state. On the other hand, a number of studies have reported on the effects of several antioxidants, anti-inflammatory agents and of mitochondrial cofactors (also termed mitochondrial nutrients, MNs) in counteracting or slowing carcinogenesis, or in controlling cancer growth. In the available literature, a body of evidence points on the roles of anti-inflammatory agents and of individual MNs against carcinogenesis or in controlling cancer cell proliferation, but only a few reports on the combined use of two or the effect of three MNs. These combinations are proposed as potentially successful tools to counteract carcinogenesis in prospective animal model studies or in adjuvant cancer treatment strategies. A "triad" of MNs are suggested to restore redox balance, mitigate side effects of prooxidative anticancer drugs, or aid in cancer prevention and/or adjuvant therapy. By elucidating their mechanistic underpinnings and appraising their clinical efficacy, we aim to contribute with a comprehensive understanding of these therapeutic modalities.

Harnessing Dual-Responsive Polymeric Micelles for Precision Oxidative Stress Amplification in Targeted Cancer Therapy.

Targeting the altered redox balance in cancer cells, this study explores a strategy to induce selective cancer cell death by combining reactive oxygen species (ROS) generation with glutathione (GSH) depletion. We developed oxidative stress-amplifying polymeric (pCB) micelles that function both as therapeutic agents and carriers for GSH-depleting retinoic acid prodrug (BRDP). pCB incorporating ROS-generating cinnamaldehyde and a GSH-depleting quinone methide precursor could self-assemble into micelles encapsulating BRDP, delivering both ROS generators and GSH-depleting drugs. The micelles were surface-functionalized with the tripeptide Arg-Gly-Asp (RGD) for targeted delivery to integrin-overexpressing tumors. In a mouse xenograft model, RGD-decorated BRDP-loaded micelles significantly accumulated in tumor sites, enhancing anticancer efficacy without toxicity to normal tissues. This study marks significant advancement in the field of oxidative stress-amplifying polymeric precursors, presenting a novel and highly effective anticancer therapeutic approach that integrates multiple tumor-specific triggers and ROS-mediated mechanisms.

Glucosinolates Mediated Regulation of Enzymatic Activity in Response to Oxidative Stress in Brassica spp.

Brassica crops are vital as they supply essential minerals, antioxidants, and bioactive substances like anthocyanins, glucosinolates, and carotenoids. However, biotic and abiotic elements that cause oxidative stress through heavy metals and other eco-toxicants pose a risk to Brassica plants. Increased generation of Reactive Oxygen Species (ROS) causes oxidative stress, which damages biomolecules and interferes with plant growth, productivity, and cellular equilibrium. Plants producing Brassica need an intricate enzyme defence mechanism to fend off oxidative stress. All the enzymes that have been addressed are found in mitochondria, peroxisomes, chloroplasts, and other cell components. They are in charge of removing ROS and preserving the cell’s redox balance. Additionally, Brassica plants use secondary metabolites called Glucosinolates (GLs), which have the capacity to regulate enzymatic activity and act as antioxidants. By breaking down compounds like sulforaphane, GLs boost antioxidant enzymes and provide protection against oxidative stress. To develop methods for improving agricultural crop stress tolerance and productivity in Brassica, it is necessary to comprehend the dynamic interaction between GL metabolism and enzymatic antioxidant systems. This highlights the possibility of maximizing antioxidant defences and raising the nutritional and commercial value of Brassica across the globe by utilizing genetic diversity and environmental interactions.

Antioxidants in neuropsychiatric disorder prevention: neuroprotection, synaptic regulation, microglia modulation, and neurotrophic effects

Oxidative stress, caused by an imbalance between the generation of reactive oxygen species (ROS) and the body’s intrinsic antioxidant defenses, plays a critical role in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. Beyond these conditions, recent evidence indicates that dysregulated redox balance is implicated in neuropsychiatric disorders, including schizophrenia, major depressive disorder, and anxiety disorders. Preclinical and clinical studies have demonstrated the potential of antioxidants, such as N-acetylcysteine, sulforaphane, alpha-lipoic acid, L-carnitine, ascorbic acid, selenocompounds, flavones and zinc, in alleviating neuropsychiatric symptoms by mitigating excitotoxicity, enhancing synaptic plasticity, reducing microglial overactivation and promoting synaptogenesis. This review explores the role of oxidative stress in the pathogenesis of neuropsychiatric disorders. It provides an overview of the current evidence on antioxidant therapy’s pharmacological effects, as demonstrated in animal models and clinical studies. It also discusses the underlying mechanisms and future directions for developing antioxidant-based adjuvant therapies. Given the limitations and side effects of existing treatments for neuropsychiatric disorders, antioxidant therapy presents a promising, safer alternative. Further research is essential to deepen our understanding and investigate the clinical efficacy and mechanisms underlying these therapies.

Photocatalytic therapy via photoinduced redox imbalance in biological system

Redox balance is essential for sustaining normal physiological metabolic activities of life. In this study, we present a photocatalytic system to perturb the balance of NADH/NAD+ in oxygen-free conditions, achieving photocatalytic therapy to cure anaerobic bacterial infected periodontitis. Under light irradiation, the catalyst TBSMSPy+ can bind bacterial DNA and initiate the generation of radical species through a multi-step electron transfer process. It catalyzes the conversion from NADH to NAD+ (the turnover frequency up to 60.7 min−1), inhibits ATP synthesis, disrupts the energy supply required for DNA replication, and successfully accomplishes photocatalytic sterilization in an oxygen-free environment. The catalyst participates in the redox reaction, interfering with the balance of NADH/NAD+ contents under irradiation, so we termed this action as photoinduced redox imbalance. Additionally, animal experiments in male rats also validate that the TBSMSPy+ could effectively catalyze the NADH oxidation, suppress metabolism and stimulate osteogenesis. Our research substantiates the concept of photoinduced redox imbalance and the application of photocatalytic therapy, further advocating the development of such catalyst based on photoinduced redox imbalance strategy for oxygen-free phototherapy.

H2S-Scavenging Hydrogel Alleviating Mitochondria Damage to Control Periodontitis.

H2S, as a typical metabolite of periodontal pathogens, exhibits a clear positive correlation with the occurrence and development of periodontitis. H2S at physiological concentrations can regulate many biological processes. However, excess H2S in the periodontal pocket can trigger secretion of proinflammatory cytokines, cause oxidative stress, and result in mitochondrial damage and cell death in human gingival fibroblasts, exacerbating periodontitis development and periodontal tissue destruction. Worse, H2S facilitates bacteria survival and proliferation by maintaining bacterial redox balance and enhancing antibiotic resistance. Unfortunately, scavenging H2S during periodontitis treatment is usually ignored. Herein, a kind of hyaluronic acid methacryloyl/ZnO (HMZ) composite hydrogel with an H2S-scavenging ability was prepared to enhance periodontitis treatment. The HMZ hydrogel possessed good injectability and cytocompatibility and was able to remove H2S by a reaction with ZnO. As a result, the HMZ hydrogel was able to increase cell viability from 13% to 120% for human gingival fibroblasts and 22% to 94% for human periodontal ligament fibroblasts at 48 h, restore mitochondrial homeostasis, and alleviate cGAS-STING signaling pathway-mediated inflammation. Meanwhile, the HMZ hydrogel showed satisfactory antibacterial properties and efficiency of plaque biofilm removal. The in vivo results further confirmed that HMZ hydrogel decreased the concentration of H2S within the periodontal pocket from 0.7 to 0.8 mM to the normal level (0.3 to 0.4 mM), killed the bacteria in the periodontal tissues, inhibited osteoclast activity, relieved excess inflammation, and decreased the vertical distance between the cementoenamel junction and the alveolar bone crest from 1,175 µm to 798 µm on the 7th day and from 1,075 µm to 693 µm on the 14th day, achieving efficient periodontal bone regeneration. In brief, an H2S scavenging-based promising strategy was developed to enhance the therapeutic efficiency of periodontitis.

Effects of serotonergic manipulation in the brainstem and hypothalamus of overnourished rats during lactation

Previous studies suggest that being overweight and obese is capable of altering brain function during critical periods due to the higher plasticity of the brain during development. However, more literature still needs to be on the immediate effect of overnutrition and serotonin modulation in brain areas. In this study, we aimed to evaluate the effects of serotoninergic manipulation on oxidative stress and pro-inflammatory markers in the brainstem and hypothalamus of overnourished rats. The fluoxetine treatment was performed from postnatal day 3 (PND3) to postnatal day 21 (PND21) to evaluate mitochondrial function, oxidative balance, and the mRNA levels of monoaminergic molecules such as serotonin and dopamine, pro-inflammatory cytokines, and BDNF. Neonatal overnutrition induces molecular and biochemical changes in the brainstem and hypothalamus. These nutritional disturbances during lactation dysregulate energy balance and cellular redox, inducing oxidative stress. Conversely, modulation of the serotoninergic system through pharmacological use of fluoxetine was able to reverse the deleterious effects of overnutrition during lactation, enabling better brain development and delaying the development of pathologies and oxidative stress.

Identification of the FBN gene family in tomato and functional analysis of SlFBN11 in the electron transport under low night temperature

FBNs are lipid-associated proteins that play a critical role in plant growth and stress response. However, the mechanisms of how FBNs proteins participate in the low night temperature response in tomato still unclear. Here we conducted a comprehensive genome-wide analysis of the FBN gene family in Solanum lycopersicum. In total, 14 SlFBN genes were identified, and information on their gene structures, protein motifs, phylogenetic relationships, and stress-related cis-regulatory elements (CREs) was provided. Among these, SlFBN11 was selected as a promising candidate for further functional characterization. The silencing of SlFBN11 destroys the redox balance of the PSI reaction center under low night temperature (LNT) stress, which led to increased ROS accumulation. Surprisingly, we found that the silencing of SlFNR2 also displayed an imbalance in electron transport of the PSI under LNT stress. Further experiments showed SlFBN11 can interact with SlFNR2 to positively response electron transport low night temperature. Collectively, the study provides a comprehensive analysis of the FBN genes family in Solanum lycopersicum and provides a theoretical basis for our understanding of the function of FBN genes in adaptation to LNT stresses.

The ABC transporter Opp imports reduced glutathione, while Gsi imports glutathione disulfide in Escherichia coli

Glutathione is the major thiol-based antioxidant in a wide variety of biological systems, ranging from bacteria to eukaryotes. As a redox couple, consisting of reduced glutathione (GSH) and its oxidized form, glutathione disulfide (GSSG), it is crucial for the maintenance of the cellular redox balance. Glutathione transport out of and into cellular compartments and the extracellular space is a determinant of the thiol-disulfide redox state of the organelles and bodily fluids in question, but is currently not well understood. Here we use the genetically-encoded, glutathione-measuring redox probe Grx1-roGFP2 to comprehensively elucidate the import of extracellular glutathione into the cytoplasm of the model organism Escherichia coli. The elimination of only two ATP-Binding Cassette (ABC) transporter systems, Gsi and Opp, completely abrogates glutathione import into E. coli’s cytoplasm, both in its reduced and oxidized form. The lack of only one of them, Gsi, completely prevents import of GSSG, while the lack of the other, Opp, substantially retards the uptake of reduced glutathione (GSH).

Optimisation of coumaric acid production from aromatic amino acids in Kluyveromyces marxianus

Yeasts are attractive hosts for the production of heterologous products due to their genetic tractability and relative ease of growth. While the baker’s yeast Saccharomyces cerevisiae is a powerful workhorse of the biotechnology industry, the species has metabolic limitations and it is critical that we develop alternative platforms that will facilitate the development of bioprocesses that rely on sustainable feedstocks. In this study, we used synthetic biology tools to construct coumaric acid–producing strains of Kluyveromyces marxianus, a yeast whose physiological traits render it attractive for biotechnology applications. Coumaric acid is a building block in the synthesis of many different families of aromatics and is a key precursor for the synthesis of complect phenylpropanoid molecules, including many flavours and aromas. The starting point for this work was a K. marxianus chassis strain that has increased flux towards the synthesis of tyrosine and phenylalanine, the aromatic amino acids that can serve as starting points for coumaric acid synthesis. Following principles of synthetic biology, a modular approach was taken to identify the best solution to different metabolic possibilities and these were then combined in different ways. For the first step, it was established that the route from phenylalanine was superior to that from tyrosine and the combined overexpression of PlPAL, AtC4H and AtCPR1 delivered the highest yield of coumaric acid. Next, it was established that while Pdc5 and Aro10 both had phenylpyruvate decarboxylase activity, inactivation of ARO10 was sufficient to prevent flux loss in the pathway. Since phenylalanine is the starting point, efforts were made to improve efficiency of its production. It was found that glutamate was a preferred nitrogen source for coumaric acid production, and this knowledge was used to engineer a strain that overexpressed S. cerevisiae GDH1 and delivered higher yields of coumaric acid. Ultimately, this strategy led to the development of strains that has yields of up to 48mg coumaric acid /g glucose. Strains were evaluated in bioreactors to investigate the effects of different process parameters. These analyses indicated that engineered strains face some redox balance challenges and further work will be required overcome these to develop strains that can perform well under industrial conditions.

Photo-controlled multifunctional hydrogel for photothermal sterilization and microenvironment amelioration of infected diabetic wounds

Diabetic foot ulcers are linked to a high disability rate, with no effective treatment currently available. Addressing infection, reducing oxidative stress, and safely managing chronic inflammation remain major challenges. In this study, a composite hydrogel dressing was developed using natural substances or clinically approved components (dopamine, D-alpha-tocopheryl polyethylene glycol succinate, and rhein). Upon near-infrared laser irradiation, the composite system rapidly heats and solidifies into a gel with photothermal antibacterial properties. Additionally, the decomposition of hydrogen peroxide releases oxygen, alleviating wound hypoxia. The hydrogel exhibited strong bactericidal activity against multiple bacterial strains. Without laser irradiation, the hydrogel effectively scavenged various free radicals and intracellular reactive oxygen species, restoring redox balance. Furthermore, it significantly reduced the expression of inflammatory cytokines, including interleukin-6 and interleukin-1β. In a diabetic mouse wound model infected with S. aureus, the mild photothermal therapy, combined with the antibacterial action of rhein, effectively managed bacterial infections, reduced inflammation, and promoted wound healing. Consequently, the photo-controlled therapeutic approach, offering antibacterial, antioxidant, and anti-inflammatory effects, holds promise for the effective treatment and management of infected diabetic wounds.

Melittin - the main component of bee venom: a promising therapeutic agent for neuroprotection through keap1/Nrf2/HO-1 pathway activation

The Nuclear factor erythroid 2–related factor (Nrf2)/ Heme oxygenase-1 (HO-1) pathway, known for its significant role in regulating innate antioxidant defense mechanisms, is increasingly being recognized for its potential in neuroprotection studies. Derived from bee venom, melittin's neuroprotective effects have raised interest. This study confirmed that melittin specificity upregulated the weakened Nrf2/HO-1 signaling in mice brain. Interestingly, we also revealed melittin’s efficient tactic, as it was suggested to first restore redox balance and then gradually stabilized other regulations of the mouse hippocampus. Using a neuro-stress-induced scopolamine model, chromatography and mass spectrometry analysis revealed that melittin crossed the compromised blood–brain barrier and accumulated in the hippocampus, which provided the chance to interact directly to weakened neurons. A wide range of improvements of melittin action were observed from various tests from behavior Morris water maze, Y maze test to immune florescent staining, western blots. As we need to find out what is the focus of melittin action, we conducted a careful observation in mice which showed that: the first signs of changes, in the hippocampus, within 5 h after melittin administration were the restoration of the Nrf2/HO-1 system and suppression of oxidative stress. After this event, from 7 to 12.5 h after administration, a diversity of conditions was all ameliorated: inflammation, apoptosis, neurotrophic factors, cholinergic function, and tissue ATP level. This chain reaction underscores that melittin focus was on redox balance's role, which revived multiple neuronal functions. Evidence of enhancement in the mouse hippocampus led to further exploration with hippocampal cell line HT22 model. Immunofluorescence analysis showed melittin-induced Nrf2 translocation to the nucleus, which would initiating the translation of antioxidant genes like HO-1. Pathway inhibitors pinpointed melittin's direct influence on the Nrf2/HO-1 pathway. 3D docking models and pull-down assays suggested melittin's direct interaction with Keap1, the regulator of the Nrf2/HO-1 pathway. Overall, this study not only highlighted melittin specifically effect on Nrf2/HO-1, thus rebalancing cellular redox, and also showed that this is an effective multi-faceted therapeutic strategy against neurodegeneration.

The Effect of Moringa oleifera Leaf Extract on C2C12 Myoblast Proliferation and Redox Status Under Oxidative Insult

Skeletal muscle tissue can regenerate after damage through the action of satellite cells, which proliferate as myoblasts when activated. Oxidative stress, marked by high rates of reactive oxygen species (e.g., hydrogen peroxide, H2O2), impairs this process by increasing myoblast cell death. Moringa oleifera leaf extract (MOLE), known for its antioxidant properties, was tested for its protective effects on C2C12 myoblasts under oxidative stress. We assessed MOLE’s impact on total antioxidant capacity (TAC), glutathione homeostasis (GSH/GSSG), cell viability, and wound recovery. The metabolomic analysis of MOLE using an LC-MSMS ZenoTOF 7600 mass spectrometry system identified key compounds, including peculiar glucosinolates (42.1%) and flavonoids (18.8%), as well as phenolic acids (4.5%) and other significant metabolites (34.6%; among them, amino acids, vitamins, and fatty acids). H2O2 disrupted myoblast redox balance and caused cell death, but MOLE treatment restored the GSH/GSSG ratio, improved TAC, and increased cell viability. Additionally, MOLE promoted faster wound closure in myoblasts exposed to H2O2. These findings suggest that MOLE can protect C2C12 myoblasts by restoring redox balance and enhancing recovery under oxidative stress.

Glutathione mitigates aluminum toxicity in root-apex transition zone of rice through reducing aluminum absorption and maintaining redox balance

Aluminium (Al) toxicity is recognized as a major constraint on crop growth and production in acidic soils, and the transition zone (TZ) of plant root apex emerges as the major perception site of Al toxicity. Glutathione (GSH) is reported to be involved in plant responses to various abiotic stresses, but its role and mechanism under Al stress remain unknown. Here, we found that GSH significantly mitigated Al toxicity on rice as revealed by the promotion of root elongation, reduction of oxidative stress and Al absorption. GSH application scavenged Al-induced H2O2 burst by activating the ascorbate (AsA)-GSH cycle and proline synthesis in root-apex TZ, thereby alleviating oxidative stress. GSH effectively reduced Al-induced pectin increment and inhibits the H2O2-induced pectin methylesterase (PME) activity and demethylesterification degree in root-apex TZ, leading to a reduction in Al binding sites and subsequently Al deposition in cell walls, thereby attenuating the inhibitory effect of Al toxicity on cell elongation. In addition, GSH-derived phytochelatins (PCs) promoted the vacuolar Al sequestration in root-apex TZ, which alleviated Al toxicity to the cytoplasm. Taken together, our results indicate a mechanism underlying how GSH alleviates Al toxicity through influencing redox state and Al absorption in rice root-apex TZ.

Redox Control of Seed Germination is Mediated by the Crosstalk of Nitric Oxide and Reactive Oxygen Species.

Significance: Seed germination and seedling establishment are characterized by changes in the intracellular redox state modulated by accelerated production of nitric oxide (NO) and reactive oxygen species (ROS). Redox regulation and enhanced accumulation of NO and ROS, approaching excessively high levels during seed imbibition, are critically important for breaking endodormancy and inducing germination. Recent Advances: Upon depletion of oxygen under the seed coat, NO is produced anaerobically in the reductive pathway associated mainly with mitochondria, and it participates in the energy metabolism of the seed until radicle protrusion. NO turnover involves nitrate reduction to nitrite in the cytosol, nitrite reduction to NO in mitochondria, and NO oxygenation in the cytosol in the reaction involving the hypoxically induced class 1 phytoglobin. In postgerminative degradation of seed tissues, NO and ROS are involved in redox signaling via post-translational modification of proteins and mediation of phytohormonal responses. Critical Issues: The crosstalk between the cellular redox potential, NO, ROS, and phytohormones integrates major physiological processes related to seed germination. Intensive accumulation of NO and ROS during imbibition is critically important for breaking seed dormancy. Upon oxygen depletion, NO and other nitrous oxides (NOx) are produced anaerobically and support energy metabolism prior to radicle protrusion. Future Directions: The turnover of NOx and ROS is determined by the intracellular redox balance, and it self-controls redox and energy levels upon germination. The particular details, regulation of this process, and its physiological significance remain to be established. Antioxid. Redox Signal. 00, 000-000.

Tumor-Specific Protein Induced in Situ Self-Assembly of Peptide Drugs for Synergistic Mitochondria Disruption.

Mitochondria-targeted cancer therapy is an effective method for controlling tumor growth. However, the presence of repair mechanisms in tumor cells in response to mitochondrial damage poses significant challenges for treatment. By taking advantage of intracellular self-assembly technology, a peptide nanomaterial, RC-K-FX, that enters tumor cells in a monomeric form is designed. After binding to MUC1-C inside the cell membrane, RC-K-FX assembles into a spherical structure that stably encapsulates MUC1-C, inhibiting its dimerization and blocking the repair of stress-induced mitochondrial damage in tumor cells. Moreover, the self-assembled mitochondrial toxic peptide effectively destroys the mitochondria, and the loss of mitochondrial repair significantly increases tumor cytotoxicity by disrupting the redox balance, enhancing reactive oxygen species (ROS), inhibiting the nuclear factor (NF)-κB pathway, and suppressing the epithelial-mesenchymal transition (EMT) process. After intravenous administration, RC-G-FX accumulated at the tumor site, exhibiting improved anti-tumor effects and extending the overall survival of tumor-bearing mice. Therefore, the integration of the in situ self-assembly of peptide drugs and damage to mitochondrial repair mechanisms provides effective therapeutic options for malignancy.

MnSOD Mimetics in Therapy: Exploring Their Role in Combating Oxidative Stress-Related Diseases

Reactive oxygen species (ROS) are double-edged swords in biological systems—they are essential for normal cellular functions but can cause damage when accumulated due to oxidative stress. Manganese superoxide dismutase (MnSOD), located in the mitochondrial matrix, is a key enzyme that neutralizes superoxide radicals (O2•−), maintaining cellular redox balance and integrity. This review examines the development and therapeutic potential of MnSOD mimetics—synthetic compounds designed to replicate MnSOD’s antioxidant activity. We focus on five main types: Mn porphyrins, Mn salens, MitoQ10, nitroxides, and mangafodipir. These mimetics have shown promise in treating a range of oxidative stress-related conditions, including cardiovascular diseases, neurodegenerative disorders, cancer, and metabolic syndromes. By emulating natural antioxidant defenses, MnSOD mimetics offer innovative strategies to combat diseases linked to mitochondrial dysfunction and ROS accumulation. Future research should aim to optimize these compounds for better stability, bioavailability, and safety, paving the way for their translation into effective clinical therapies.

Induction of Alkaline Bands in Chara by External Electric Current Reveals the Influence of Plasma Membrane H+ Fluxes on Cyclosis-Mediated Signaling

Long-distant communications in plants and giant plant cells are essential for optimal cell functioning under variable environmental conditions. In characean internodal cells exposed to spotted or flickering light, the redox balance in dimly lit chloroplasts is sensitive to the reducing power produced in brightly illuminated chloroplasts of a distal cell region located upstream in the directed cytoplasmic flow. The distant communication is mediated by excessive production in the high-light region of reducing metabolites that are exported into the streaming cytoplasm and delivered by cytoplasmic flow to light-starving chloroplasts. These target chloroplasts perceive the transportable metabolic signal, which is reflected in the transient increase of modulated chlorophyll fluorescence F '. Previous studies of cyclosis-mediated F ' transients revealed that they are sensitive to natural H+ fluxes across the plasma membrane and that the signal transduction is suppressed in cell areas with massive H+ influx. In this study with Chara australis R. Br., we show that the injection of inward electric current is accompanied by proton influx sufficient for the creation of artificial alkaline band. The combined application of PAM chlorophyll microfluorometry, local light stimuli, and measurements of pericellular pH showed that the microfluidic signal transduction is notably suppressed under artificially produced alkaline band where H+ influx acidifies the cytoplasm. It is hypothesized that changes in cytoplasmic pH regulate the rates of electron flows directed to NADP reduction and O2 reduction, which may disturb long-distance redox control system involving production and consumption of reducing equivalents.

Extracts from Tartary Buckwheat Sprouts Restricts Oxidative Injury Induced by Hydrogen Peroxide in HepG2 by Upregulating the Redox System

Oxidative stress, which results from an overproduction of reactive oxygen species (ROS), can cause damage that may contribute to a range of metabolic disorders. Antioxidants are considered to upregulate the activity of antioxidant enzymes, which are crucial for eliminating excess ROS and safeguarding the body against oxidative stress-induced damage. In the present study, the effect of polyphenol extracts from tartary buckwheat sprouts (TBSE) on the redox system of HepG2-cell-induced oxidative injury by hydrogen peroxide were investigated for evaluating the protective effect and mechanism of tartary buckwheat sprouts (TBS). The results revealed that TBSE that had sprouted for a period of 10 days possessed six predominant phenolic compounds, ranked from the most abundant to the least: chlorogenic acid, syringic acid, caffeic acid, rutin, ferulic acid, and quercetin. TBSE could successfully inhibit H2O2-induced ROS overproduction, restore and balance the mitochondrial membrane potential, while also significantly increasing cellular antioxidant activity (CAA) and the expression of protective enzymes such as SOD, CAT, and GST. More interestingly, treating HepG2 cells with TBSE triggered the translocation of Nrf2 to the nucleus, accompanied by a negative feedback mechanism involving Keap1. Therefore, it regulated the downstream production of antioxidant enzymes, including NQO1 and HO-1. Overall, this finding suggested that TBSE could restore the redox state of H2O2-resistant HepG2 cells, indicating TBSE protected cells from H2O2-induced oxidative stress significantly. Beneficial resistance and effects on redox balance were attributed to activation of Nrf2. Present work revealed the potential health benefits of TBS and provided a test basis for developing functional food of TBS.

Mitochondrial Redox Status Regulates Glycogen Metabolism via Glycogen Phosphorylase Activity.

Mitochondria and glycogen are co-distributed in skeletal muscles to regulate the metabolic status. Mitochondria are also redox centers that regulate the muscle function during exercise. However, the pathophysiological relationship between the mitochondrial redox status and glycogen metabolism in the muscle remains unclear. In the present study, we examined the pathological effects of mitochondrial dysfunction induced by mitochondrial superoxide dismutase (SOD2) depletion on glycogen metabolism. We found that muscle glycogen was significantly accumulated in association with motor dysfunction in mice with a muscle-specific SOD2 deficiency. Muscle glycogen phosphorylase (GP-M) activity, which is a key enzyme for glycogen degradation at times when energy is needed (e.g., during exercise), was significantly decreased in the mutant muscle. Moreover, the GP-M activity on normal muscle sections decreased after treatment with paraquat, a superoxide generator. In contrast, treatment with antioxidants reversed the GP-M activity and motor disturbance of the mutant mice, indicating that GP-M activity was reversibly regulated by the redox balance. These results demonstrate that the maintenance of the mitochondrial redox balance regulates glycogen metabolism via GP-M activity.