NADPH Oxidase Activity Research Articles

HRAMS Proteomics Insights on the Anti-Filarial Effect of Ocimum sanctum: Implications in Phytochemical-Based Drug-Targeting and Designing.

Lymphatic filariasis (LF) continues to impact 657 million individuals worldwide, resulting in lifelong and chronic impairment. The prevalent anti-filarial medications-DEC, albendazole, and ivermectin-exhibit limited adulticidal efficacy. Despite ongoing LF eradication programs, novel therapeutic strategies are essential for effective control. This study examines the mechanism of action of Ocimum sanctum on the filarial parasites Setaria cervi via a synergistic biochemical and proteomics methodology. The ethanolic extract of Ocimum sanctum (EOS) demonstrated potential anti-filarial action in the MTT reduction experiment, with an LC50 value of 197.24 µg/mL. After EOS treatment, an elevation in lipid peroxidation (51.92%), protein carbonylation (48.99%), and NADPH oxidase (88.88%) activity, along with a reduction in glutathione (GSH) (-39.23%), glutathione reductase (GR) (-60.17%), and glutathione S transferase (GST) (-50.48%) activity, was observed. The 2D gel electrophoresis identified 20 decreased and 11 increased protein spots in the EOS-treated parasites relative to the control group. Additionally, in drug docking analysis, the EOS bioactive substances ursolic acid, rutin, and rosmarinic acid show a significant binding affinity with the principal differentially expressed proteins. This paper demonstrates, for the first time, that the anti-filarial efficacy of EOS is primarily facilitated by its impact on energy metabolism, antioxidant mechanisms, and stress response systems of the parasites.

Bovine PMN responses to extracellular vesicles released by Besnoitia besnoiti tachyzoites and B. besnoiti-infected host cells

Bovine besnoitiosis is a re-emerging cattle disease caused by the apicomplexan parasite Besnoitia besnoiti, which severely affects individual animal welfare and profitability in cattle industry. We recently showed that B. besnoiti tachyzoite exposure to bovine polymorphonuclear neutrophils (PMN) effectively triggers neutrophil extracellular trap (NET) formation, leading to parasite immobilization hampering host cell infection. So far, the triggers of this defense mechanism remain unclear. Emerging evidence indicates that extracellular vesicles (EVs) modulate PMN effector functions, such as ROS production or NET formation. Therefore, we tested whether exposure of bovine PMN to EVs from different cellular sources affects classical PMN effector functions and cytokine/chemokine secretion. EVs were isolated from B. besnoiti-infected and non-infected host cells (bovine umbilical vein endothelial cells, BUVEC), from tachyzoite-exposed bovine PMN and from B. besnoiti tachyzoites. EV concentration and size was determined by Nano-Flow cytometry and EV nature was confirmed by both classical EV markers (CD9 and CD81) and transmission electron microscopy (TEM). Overall, PMN stimulation with both BUVEC- and tachyzoite-derived EVs significantly induced extracellular DNA release while EVs from PMN failed to affect NET formation. BUVEC and tachyzoite EV-driven NET formation was confirmed microscopically by the presence of DNA decorated with neutrophil elastase (NE) and histones in typical NET structures. Moreover, confocal microscopy revealed EVs to be internalized by bovine PMN. Referring to PMN activation, EVs from the different cellular sources all failed to affect glycolytic or oxidative responses of bovine PMN as detected by Seahorse®-based analytics and luminol-based chemoluminescence, thereby denying any role of NADPH oxidase (NOX) activity in EV-driven NET formation. Finally, exposure to B. besnoiti-infected BUVEC-derived EVs induced IL-1β and IL-6 release, but failed to drive CXCL8 release of bovine PMN. Hence, we overall demonstrated that EVs of selected cellular origin owned the capacity to trigger NOX-independent NET formation, were incorporated by PMN and selectively fostered IL-1β and IL-6 release.

C-Peptide Ameliorates Particulate Matter 2.5-Induced Skin Cell Apoptosis by Inhibiting NADPH Oxidation

Connecting peptide (C-peptide), a byproduct of insulin biosynthesis, has diverse cellular and biological functions. Particulate matter 2.5 (PM2.5) adversely affects human skin, leading to skin thickening, wrinkle formation, skin aging, and inflammation. This study aimed to investigate the protective effects of C-peptide against PM2.5-induced damage to skin cells, focusing on oxidative stress as a key mechanism. C-peptide mitigated NADPH oxidation and intracellular reactive oxygen species (ROS) production induced by PM2.5. It also suppressed PM2.5-induced NADPH oxidase (NOX) activity and alleviated PM2.5-induced NOX1 and NOX4 expression. C-peptide protected against PM2.5-induced DNA damage, lipid peroxidation, and protein carbonylation. Additionally, C-peptide mitigated PM2.5-induced apoptosis by inhibiting intracellular ROS production. In summary, our findings suggest that C-peptide mitigates PM2.5-induced apoptosis in human HaCaT keratinocytes by inhibiting intracellular ROS production and NOX activity.

SnRK1α1-mediated RBOH1 phosphorylation regulates reactive oxygen species to enhance tolerance to low nitrogen in tomato.

Nitrogen is essential for plant growth and development. SNF1-related protein kinase 1 (SnRK1) is an evolutionarily conserved protein kinase pivotal for regulating plant responses to nutrient deficiency. Here, we discovered that the expression and activity of the SnRK1 α-catalytic subunit (SnRK1α1) increased in response to low-nitrogen stress. SnRK1α1 overexpression enhanced seedling tolerance, nitrate uptake capacity, apoplastic reactive oxygen species (ROS) accumulation, and NADPH oxidase activity in tomato (Solanum lycopersicum L.) under low-nitrogen stress compared to wild type plants, while snrk1α1 mutants exhibited the opposite phenotypes. Mutation of the NADPH oxidase gene Respiratory burst oxidase homolog 1 (RBOH1) suppressed numerous nitrate uptake and metabolism genes during low-nitrogen stress. rboh1 mutants displayed lower NADPH oxidase activity, apoplastic ROS production, and seedling tolerance to low nitrogen. Silencing RBOH1 expression also compromised SnRK1α1-mediated seedling tolerance to low-nitrogen stress. SnRK1α1 interacts with and activates RBOH1 through phosphorylation of three N-terminal serine residues, leading to increased apoplastic ROS production and enhanced tolerance to low nitrogen conditions. Furthermore, RBOH1-dependent ROS oxidatively modified the transcription factor TGA4 at residue Cys-334, which increased NRT1.1 and NRT2.1 expression under low-nitrogen stress. These findings reveal a SnRK1α1-mediated signaling pathway and highlight the essential role of RBOH1-dependent ROS production in enhancing plant tolerance to low nitrogen.

Therapeutic potential of beta‐carotene on intracisternal injection of glucose oxidase‐induced senile dementia in diabetic rats

Abstract BackgroundSenile dementia (SD) is a deteriorative organic brain disorder and it comprises Alzheimer’s disease (AD) as a major variant. SD is shown impairment of mental capacities whereas AD is degeneration of neurons. According to World Health Organization (WHO) report; more than 55 million peoples have dementia and it is raising 10 million new cases every year. Further, it is expected to rise to 78 million in 2030 and triple by 2050. The glucose oxidase (E.C. 1.1.3.4; GOD) is an oxidoreductase enzyme and it oxidizes the β‐d‐glucose to d‐glucono‐δ‐lactone and hydrogen peroxide (H2O2). In the neuronal system, GOD & H2O2 cause rapid fluctuations of glucose levels, insulin resistance, oxidative stress along with microglial activation and neurodegenerations. Besides, only a few medications were approved for the symptomatic relief of SD i.e., donepezil, galantamine, rivastigmine, and memantine. Moreover, the most efficient and potential agents are not discovered yet. Hence, the present study was designed to investigate the beta‐carotene (BC) actions against the GOD‐associated SD in diabetic rats.MethodMale Sprague Dawley rats were used for the induction of diabetes by intraperitoneal injection of nicotinamide (50 mg/kg and streptozotocin 50 mg/kg), and SD was induced by intracisternal administration of GOD (50 U/5 µl at 1 µL/minute). The BC (50 and 100 mg/kg; p.o.) and donepezil (1 mg/kg; p.o.) were administered for 15 consecutive days. The cognitive function was assessed by the Morris water maze test and biomarkers i.e., blood glucose & insulin; serum nitric oxide (NO); tissue acetylcholinesterase (AChE), galectin‐1 (G1), NADPH oxidase (NOX4) activity & glucose transporter 1 (GLUT1) levels were evaluated.ResultGOD potentially changes the neurovascular unit in the brain which leads to a rise the insulin resistance (IR), NO, G1, & GLUT1 levels; and decreases the NOX4 activity. The GOD causes the potential cognitive dysfunctions. However, the treatment of BC attenuated the GOD‐associated cognitive dysfunction and biomarker changes.ConclusionThe present results revealed that BC possesses the ameliorative potential against GOD‐induced neurotoxicity and SD due to its anti‐oxidative, anti‐cholinesterase, reduction of IR, prevention of microglial activation, and enhancement of the glucose update actions.

Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

In neurodegenerative processes of the brain, the hippocampus is primarily damaged with subsequent cognitive impairments as a result of increased generation of reactive oxygen species and reactive nitrogen species, which lead to apoptosis and necrosis of neurons. Cell therapy with the use of mesenchymal stromal cells (MSCs) has shown encouraging results regarding endogenous mechanisms of neuroregeneration in response to ischemic injury of brain structures. The work aimed to study the therapeutic potential of MSCs of various origins and sources, MSCs lysate and reference drug citicoline on the energy component of neuronal metabolism, oxidative and nitrosative stress in the rat hippocampus under conditions of cerebral ischemia-reperfusion (IR). Material and methods. The experiment was carried out on 126 Wistar rats with modeled pathology (20-minute IR of the internal carotid arteries), which were injected with MSCs derived from Wharton’s jelly of the human umbilical cord, MSCs derived from human and rat adipose tissues, rat embryonic fibroblasts, MSCs lysate and citicoline immediately after removal of the ligatures. Biochemical parameters of carbohydrate metabolism (glucose, lactate), oxidative (NADPH oxidase activity) and nitrosative stress (NO synthase activity) in the rat hippocampus were determined on days 7 and 14 after IR under the conditions of cerebral IR and on the background of its correction. Results. It was established that during IR in the rat hippocampus of the brain, the content of glucose and lactate increases, the process of aerobic oxidation of glucose is inhibited, anaerobic glycolysis increases, lactic acidosis develops in hippocampal cells, the level of NADPH oxidase activity decreases, and an imbalance occurs in the functioning of the nitrogen monoxide system. A positive effect of human umbilical cord Wharton’s jelly-derived MSC and rat embryonic fibroblasts transplantation, and the use of citicoline on the stabilization of glucose, lactate, NADPH-oxidase and nitric oxide levels was found. Transplantation of human and rat adipose-derived MSCs was significantly less effective than citicoline and demonstrated no statistically significant modulatory effect on biochemical parameters in the hippocampus of experimental animals with IR. Conclusions. Transplantation of the human umbilical cord Wharton’s jelly-derived MSCs was not inferior to the citicoline and, better than other tested MSCs and their lysate, contributed to the recovery of disturbed energy processes (glucose level) and eliminated metabolic acidosis (lactate level) in the hippocampus of rats, i.e. had a positive modulating effect on the oxidant-antioxidant balance (NADPH oxidase activity level).

Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

In neurodegenerative processes of the brain, the hippocampus is primarily damaged with subsequent cognitive impairments as a result of increased generation of reactive oxygen species and reactive nitrogen species, which lead to apoptosis and necrosis of neurons. Cell therapy with the use of mesenchymal stromal cells (MSCs) has shown encouraging results regarding endogenous mechanisms of neuroregeneration in response to ischemic injury of brain structures. The work aimed to study the therapeutic potential of MSCs of various origins and sources, MSCs lysate and reference drug citicoline on the energy component of neuronal metabolism, oxidative and nitrosative stress in the rat hippocampus under conditions of cerebral ischemia-reperfusion (IR). Material and methods. The experiment was carried out on 126 Wistar rats with modeled pathology (20-minute IR of the internal carotid arteries), which were injected with MSCs derived from Wharton’s jelly of the human umbilical cord, MSCs derived from human and rat adipose tissues, rat embryonic fibroblasts, MSCs lysate and citicoline immediately after removal of the ligatures. Biochemical parameters of carbohydrate metabolism (glucose, lactate), oxidative (NADPH oxidase activity) and nitrosative stress (NO synthase activity) in the rat hippocampus were determined on days 7 and 14 after IR under the conditions of cerebral IR and on the background of its correction. Results. It was established that during IR in the rat hippocampus of the brain, the content of glucose and lactate increases, the process of aerobic oxidation of glucose is inhibited, anaerobic glycolysis increases, lactic acidosis develops in hippocampal cells, the level of NADPH oxidase activity decreases, and an imbalance occurs in the functioning of the nitrogen monoxide system. A positive effect of human umbilical cord Wharton’s jelly-derived MSC and rat embryonic fibroblasts transplantation, and the use of citicoline on the stabilization of glucose, lactate, NADPH-oxidase and nitric oxide levels was found. Transplantation of human and rat adipose-derived MSCs was significantly less effective than citicoline and demonstrated no statistically significant modulatory effect on biochemical parameters in the hippocampus of experimental animals with IR. Conclusions. Transplantation of the human umbilical cord Wharton’s jelly-derived MSCs was not inferior to the citicoline and, better than other tested MSCs and their lysate, contributed to the recovery of disturbed energy processes (glucose level) and eliminated metabolic acidosis (lactate level) in the hippocampus of rats, i.e. had a positive modulating effect on the oxidant-antioxidant balance (NADPH oxidase activity level).

A transient blood IL-17 increase triggers neuroinflammation in cerebellum and motor incoordination in hyperammonemic rats

Patients with liver cirrhosis may show minimal hepatic encephalopathy (MHE) with motor incoordination which is reproduced in hyperammonemic rats. Hyperammonemia induces peripheral inflammation which triggers neuroinflammation and enhanced GABAergic neurotransmission in cerebellum and motor incoordination. The mechanisms involved remain unknown. The aims were to assess if the early increase of peripheral IL-17 triggers motor incoordination in hyperammonemic rats and to identify some underlying mechanisms. We assessed if blocking peripheral IL-17 with anti-IL-17 at 2–4 days of hyperammonemia prevents motor incoordination and analyzed underlying mechanisms. Hyperammonemia induces a transient blood IL-17 increase at days 3–4. This is associated with increased IL-17 receptor membrane expression and activation in cerebellum, leading to NADPH oxidase activation, increased superoxide production and MLCK that induce blood–brain barrier (BBB) permeabilization by reducing occludin and ZO-1. BBB permeabilization facilitates the entry of IL-17, which increases in cerebellum and activates microglia. This increases TNFα and the TNFR1-S1PR2-CCL2-BDNF-TrkB pathway. This enhances GABAergic neurotransmission which impairs motor coordination. Blocking peripheral IL-17 with anti-IL-17 prevents all the above process and prevents motor incoordination. Early treatment to reduce blood IL-17 may be a useful treatment to reverse motor incoordination in patients with MHE.Graphical abstract

Effects of sucrose and 1-MCP on enzymatic and nonenzymatic antioxidants in postharvest Gynura bicolor DC

Effects of sucrose and 1-MCP on enzymatic and nonenzymatic antioxidants in postharvest Gynura bicolor DC

Effect of elevated ammonium on biotic and abiotic stress defense responses and expression of related genes in cucumber (Cucumis sativus L.) plants

Effect of elevated ammonium on biotic and abiotic stress defense responses and expression of related genes in cucumber (Cucumis sativus L.) plants

Angiotensin type-1 receptor autoantibodies promote alpha-synuclein aggregation in dopaminergic neurons.

Angiotensin, through its type-1 receptor (AT1), is a major inducer of inflammation and oxidative stress, contributing to several diseases. Autoimmune processes have been involved in neurodegeneration, including Parkinson's disease (PD). AT1 autoantibodies (AT1-AA) enhance neurodegeneration and PD, which was related to increased neuronal oxidative stress and neuroinflammation. However, the effect of AT1-AA on α-synuclein aggregation, a major factor in PD progression, has not been studied. In cultures of dopaminergic neurons, we observed that AT1-AA promote aggregation of α-synuclein, as AT1-AA upregulated major mechanisms involved in the α-synuclein aggregation process such as NADPH-oxidase activation and intracellular calcium raising. The results further support the role of AT1 receptors in dopaminergic neuron degeneration, and several recent clinical studies observing the neuroprotective effects of AT1 receptor blockers.

Accumulation of Advanced Oxidation Protein Products Promotes Age-Related Decline of Type H Vessels in Bone.

Type H vessels have been proven to couple angiogenesis and osteogenesis. The decline of type H vessels contributes to bone loss in the aging process. Aging is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, whether AOPP accumulation is involved in age-related decline of type H vessels is unclear. Here, we show that the increase of AOPP levels in plasma and bone was correlated with the decline of type H vessels and loss of bone mass in old mice. Exposure of microvascular endothelial cells to AOPPs significantly inhibited cell proliferation, migration, and tube formation; increased NADPH oxidase activity and excessive reactive oxygen species generation; upregulated the expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1; and eventually impaired angiogenesis, which was alleviated by redox modulator N-acetylcysteine and NADPH oxidase inhibitor apocynin. Furthermore, reduced AOPP accumulation by NAC treatment was able to alleviate significantly the decline of type H vessels, bone mass loss, and deterioration of bone microstructure in old mice. Collectively, these findings suggest that AOPPs accumulation contributes to the decline of type H vessels in the aging process, and illuminate a novel potential mechanism underlying age-related bone loss.

β3-adrenergic agonist counters oxidative stress and Na+-K+ pump inhibitory S-glutathionylation of placental cells: implications for preeclampsia.

Oxidative stress from placental ischemia/reperfusion and hypoxia/reoxygenation (H/R) in preeclampsia is accompanied by Na+-K+ pump inhibition and S-glutathionylation of its β1 subunit (GSS-β1), a modification that inhibits the pump. β3-adrenergic receptor (β3-AR) agonists can reverse GSS-β1. We examined the effects of the agonist CL316,243 on GSS-β1 and sources of H/R-induced oxidative stress in immortalized first-trimester human trophoblast (HTR-8/SVneo) and freshly isolated placental explants from normal-term pregnancies. H/R increased GSS-β1 and, reflecting compromised α1/β1 subunit interaction, reduced α1/β1 pump subunit coimmunoprecipitation. H/R increased p47phox/p22phox NADPH oxidase subunit coimmunoprecipitation, reflecting membrane translocation of cytosolic p47phox that is needed to activate NADPH oxidase. Fluorescence of O2•--sensitive dihydroethidium increased in parallel. H/R increased S-glutathionylation of endothelial nitric oxide synthase (GSS-eNOS) that uncouples nitric oxide synthesis toward the synthesis of O2•- and reduced trophoblast migration. Oxidative stress induced by tumor necrosis factor α increased soluble fms-like tyrosine kinase receptor 1 (sFlt-1) trophoblast release, a marker of preeclampsia, and reduced trophoblast integration into endothelial cellular networks. CL316,243 eliminated H/R-induced GSS-β1 and decreases of α1/β1 subunit coimmunoprecipitation, eliminated NADPH oxidase activation and increases in GSS-eNOS, restored trophoblast migration, eliminated increased sFlt-1 release, and restored trophoblast integration in endothelial cell networks. H/R-induced GSS-β1, α1/β1 subunit coimmunoprecipitation, and NADPH oxidase activation of placental explants reflected effects of H/R for trophoblasts and CL316,243 eliminated these changes. We conclude a β3-AR agonist counters key pathophysiological features of preeclampsia in vitro. β3 agonists already in human use for another purpose are potential candidates for repurposing to treat preeclampsia.NEW & NOTEWORTHY H/R-induced oxidative stress and deficient NO-dependent placentation are features of preeclampsia, yet nonspecific antioxidants and NO donors are ineffective. Here, activation of the microdomain-confined signaling pathway with an agonist for the eNOS-coupled β3-AR eliminates inhibitory glutathionylation of the Na+-K+ pump's β1 subunit, uncoupling of eNOS, and activation of NADPH oxidase that are sources of H/R-induced oxidative stress. The agonist also eliminates H/R-induced inhibition of trophoblast migration and their integration into an endothelial network.

New insights into oxidative damage to yellow catfish (Pelteobagrus fulvidraco) muscle by acute ammonia stress

New insights into oxidative damage to yellow catfish (Pelteobagrus fulvidraco) muscle by acute ammonia stress

Insulin Mediates Lipopolysaccharide-Induced Inflammatory Responses and Oxidative Stress in BV2 Microglia.

Insulin, the key hormone for glucose regulation, has garnered attention for its role as an immune modulator. Impaired insulin signaling in the central nervous system is linked to neuroinflammation and neurodegenerative diseases. Microglia, the resident macrophage-like immune cells in the brain, are key regulators of neuroinflammation. However, the mechanisms by which insulin influences microglial immune responses remain relatively unknown. This study aimed to assess the effects of post-treatment with insulin [30minutes after lipopolysaccharide (LPS) exposure] on LPS-induced inflammatory responses in BV2 microglial cells. Post-treatment with insulin potentiated LPS-induced production of nitric oxide and pro-inflammatory cytokines, such as TNF and IL-6, through activation of the Akt/NF-κB pathway. Insulin also enhanced the ability of BV2 cells to phagocytose bacteria particles and β-amyloid fibrils. Conversely, insulin inhibited activation of NADPH oxidase and reduced intracellular levels of reactive oxygen species in LPS-treated BV2 cells. Insulin enhances microglial immune competence when challenged by endotoxins but mitigates oxidative stress in these cells.

CB1 Receptor Activation Provides Neuroprotection in an Animal Model of Glutamate-Induced Excitotoxicity Through a Reduction of NOX-2 Activity and Oxidative Stress.

Excitotoxicity is a process in which NADPH oxidase-2 (NOX-2) plays a pivotal role in the generation of reactive oxygen species (ROS). Oxidative stress influences the expression of Aquaporin 4 (AQP4), a water channel implicated in blood-brain barrier (BBB) permeability and edema formation. The endocannabinoid system is widely distributed in the brain, particularly through the cannabinoid receptor type 1 (CB1) and type 2 (CB2), which have been shown to have a neuroprotective function in brain injury. Given the significant involvement of NOX-2 in ROS production during excitotoxicity, our research aims to assess the participation of NOX-2 in the neuroprotective effect of the cannabinoid receptor agonist WIN55,212-2 against glutamate-induced excitotoxicity damage in the striatum using invivo model. Wild-type mice (C57BL/6) and NOX-2 KO (gp91Cybbtm1Din/J) were stereotactically injected in the striatum with monosodium glutamate or vehicle. Subsequently, a group of mice was administered an intraperitoneal dose of WIN55,212-2, AM251, or AM251/WIN55,212-2 following the intracerebral injection. Motor activity was assessed, and the lesion was examined through histological sections stained with cresyl violet. Additionally, brain water content and Evans blue assay were conducted. The activity of NOX was quantified, and the protein expression of CB1, gp91phox, AQP4, Iba-1, TNF-α, and NF-κB was analyzed using Western blot. Furthermore, ROS formation was measured through the DHE assay. The activation of the endocannabinoid receptors demonstrated a neuroprotective response during excitotoxicity, meditated by NOX-2. The reduction in ROS production led to a decrease in neuroinflammation, and AQP4 expression, resulting in reduced edema formation, and BBB permeability. During excitotoxic damage, WIN55,212-2 inhibits NOX-2-induced ROS production, reducing brain injury.

Formononetin Induces Ferroptosis in Activated Hepatic Stellate Cells to Attenuate Liver Fibrosis by Targeting NADPH Oxidase 4.

Ferroptosis is a newly discovered type of cell death that exerts a crucial role in hepatic fibrosis. Formononetin (FMN), a natural isoflavone compound mainly isolated from Spatholobus suberectus Dunn, shows multiple biological activities, including antioxidant, anti-inflammatory, and hepatoprotection. This research aims to explore the regulatory mechanism of FMN in liver fibrosis and the relationship between NADPH oxidase 4 (NOX4) and ferroptosis. The effects of FMN on HSC ferroptosis were evaluated in rat model of CCl4-induced hepatic fibrosis. In vitro, N-acetyl-L-cysteine (NAC) and deferoxamine (DFO) were used to block ferroptosis and then explored the anti-fibrotic effect of FMN. The target protein of FMN was identified by bio-orthogonal click chemistry reaction as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), surface plasmon resonance (SPR) assays, and isothermal titration calorimetry (ITC) analysis. Here, we found that FMN exerted anti-fibrotic effects via inducing ferroptosis in activated HSCs. NAC and DFO prevented FMN-induced ferroptotic cell death and collagen reduction. Furthermore, FMN bound directly to NOX4 through possible active amino acid residues sites, and increased NOX4-based NADPH oxidase activity to enhance levels of NADP+/NADPH, thus promoting ferroptosis of activated HSCs and relieving liver fibrosis. These results demonstrate that the direct target and mechanism by which FMN improves liver fibrosis, suggesting that FMN may be a natural candidate for further development of liver fibrosis therapy.

Arginine alleviates LPS-induced leukocytes inflammation and apoptosis via adjusted NODs signaling

Arginine alleviates LPS-induced leukocytes inflammation and apoptosis via adjusted NODs signaling

UV-B radiation mitigates oxidative stress damage in postharvest Agaricus bisporus by modulating the antioxidant defense system

UV-B radiation mitigates oxidative stress damage in postharvest Agaricus bisporus by modulating the antioxidant defense system

Deciphering the mechanisms underlying the neuroprotective potential of kaempferol: a comprehensive investigation.

Neurodegenerative disorders are characterized by neuronal degradation, dysfunction, or death within the CNS. Oxidative and inflammatory stress play crucial roles in the pathogenesis of various neurodegenerative diseases. The interplay between these stressors and dysregulated cellular signaling pathways contributes to neurodegeneration. Downregulation of NRF-2 compromises antioxidant defense, exacerbating neuronal damage, while increased TLR-4/MAPK and TLR-4/NF-κB signaling promotes neuroinflammation. Excessive ROS production by NADPH oxidase leads to oxidative damage and neuronal apoptosis. The strategies targeting NRF-2, TLR-4-mediated inflammatory stress, and NADPH oxidase activity promise to mitigate neuronal damage and halt the progression of the disease. Kaempferol is a flavonoid polyphenol antioxidant found abundantly in various fruits and vegetables, including apples, grapes, tomatoes, and broccoli. It is widely found in medicinal plants including Equisetum spp., Sophora japonica, Ginkgo biloba, and Euphorbia pekinensis (Rupr.). A substantial body of in vitro and in vivo evidences have demonstrated the neuroprotective potential of kaempferol against neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Kaempferol demonstrates multifaceted potential in mitigating neuroinflammation, apoptosis, and oxidative stress in different neurodegenerative diseases through the modulation of various pathways including NRF-2, NADPH oxidase, TLR-4/MAPK, and TLR-4/NF-κB. This review article was developed through a comprehensive analysis and interpretation of research published between 2009 and 2024, sourced from multiple scientific databases, including PubMed, Scopus, ScienceDirect, and Web of Science. This review aims to provide an in-depth overview of the neuroprotective effects of kaempferol, focusing on its underlying molecular mechanisms. A total of 24 research evidence were included to elucidate the molecular pathways by which kaempferol exerts its protective effects against neurodegenerative diseases.