Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

Biochanin A attenuates spinal cord injury in rats during early stages by inhibiting oxidative stress and inflammasome activation

Previous studies have shown that Biochanin A,a flavonoid compound with estrogenic effects,can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury;howeve r,its effect on spinal cord injury is still unclea r. In this study,a rat model of spinal cord injury was established using the heavy o bject impact method,and the rats were then treated with Biochanin A(40 mg/kg) via intrape ritoneal injection for 14 consecutive days.The res ults showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal co rd tissue injury,reduced inflammation and oxidative stress in spinal cord neuro ns,and reduced apoptosis and pyroptosis.In addition,Biochanin A inhibited the expression of inflammasome-related proteins(ASC,NLRP3,and GSDMD)and the Toll-like receptor 4/nuclear factor-κB pathway,activated the Nrf2/heme oxygenase 1 signaling pathway,and increased the expression of the autophagy markers LC3 Ⅱ,Beclin-1,and P62.Moreove r,the therapeutic effects of Biochanin A on early post-s pinal cord injury were similar to those of methylprednisolone.These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways.These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

Synergistic catalysis of the N-hydroxyphthalimide on flower-like bimetallic metal-organic frameworks for boosting oxidative desulfurization

Synergic catalytic effect between active sites and supports greatly determines the catalytic activity for the aerobic oxidative desulfurization of fuel oils.In this work,Ni-doped Co-based bimetallic metal-organic framework(CoNi-MOF)is fabricated to disperse N-hydroxyphthalimide(NHPI),in which the whole catalyst provides plentiful synergic catalytic effect to improve the performance of oxidative desulfurization(ODS).As a bimetallic MOF,the second metal Ni doping results in the flower-like morphology and the modification of electronic properties,which ensure the exposure of NHPI and strengthen the synergistic effect of the overall catalyst.Compared with the monometallic Co-MOF and naked NHPI,the NHPI@CoNi-MOF triggers the efficient activation of molecular oxygen and improves the ODS performance without an initiator.The sulfur removal of dibenzothiophene-based model oil reaches 96.4%over the NHPI@CoNi-MOF catalyst in 8 h of reaction.Furthermore,the catalytic product of this aerobic ODS reaction is sulfone,which is adsorbed on the catalyst surface due to the difference in polarity.This work provides new insight and strategy for the design of a strong synergic catalytic effect between NHPI and bimetallic supports toward high-activity aerobic ODS materials.

Effects of pyraclostrobin on growth,oxidative stress,and gene expression in relation to stress and ATP-binding cassette transporters in Tetrahymena thermophila

Pyraclostrobin(PYR),a widely used fungicide,has negative effects on fish and algae,but its toxicity in protozoa remains unclear.In this study,the effects of PYR on the growth,oxidative stress,and gene expression related to stress and ATP-binding cassette(ABC)transporters in Tetrahymena thermophila were investigated.The result showed that the 96-h IC_(50)of PYR against T.thermophila was 17.2 mg/L.Moreover,PYR inhibited the growth of T.thermophila in concentration-or time-dependent manner.A morphological study revealed that the shape and size of T.thermophila changed,and damage of cell membrane surface was observed by scanning electron microscopy after 96 h of PYR exposure.The activities of superoxide dismutase(SOD)and catalase(CAT)increased throughout the experiment.In contrast,the glutathione(GSH)content was increased at 24 h and 48 h of exposure and decreased at 96 h.Moreover,a significant increase in malondialdehyde(MDA)level was observed in T.thermophila after96 h of exposure.Furthermore,PYR upregulated the HSP703,HSP705,GPx2,and ABAC15 gene expression in the 0.1–5-mg/L groups and downregulated the HSP704,HSP90,TGR,and ABCC52 mRNA levels at 96 h of exposure.These results suggest that PYR may exert adverse effects on T.thermophila by inducing oxidative stress and changing the gene expression related to ABC transporters and stress,which may enrich the understanding of the toxicity mechanism of PYR in aquatic organisms and provide reference data for aquatic ecological risk assessments.

Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?

Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.

Phlorizin alleviates deltamethrin-induced oxidative stress in brine shrimp Artemia

Deltamethrin(DEL),a commonly used pyrethroid pesticide,results in higher reactive oxygen species(ROS)levels in aquatic animals,which consequently unbalance the redox state.Phlorizin(PHL)is a flavonoid and a natural product promising to prevent or reduce pesticide-induced oxidative stress.Artemia is a micro-crustacean widely used in marine hatcheries and an experimental aquatic organism for environmental toxicology research.This research aimed to evaluate the toxicity of DEL on Artemia and the antioxidative effect of PHL against the toxicity.Results show that 0.08-mg/mL PHL exerted its antioxidative effects on hatching percentage of the cysts in 24-h incubation and on body length and survival rate of Artemia in 12-d culture.After 12-d culture,12-,24-,and 36-h DEL exposure showed significant drops in SOD,CAT,and GSH-Px enzyme activities,and significant increases in ROS and malondialdehyde(MDA)levels in Artemia(P<0.05).On the contrary,0.08-mg/mL PHL application improved the enzyme activities and decreased the ROS and MDA levels(P<0.05).Moreover,0.08-mg/mL PHL significantly increased mRNA expression levels of Cu/Zn SOD,CAT,GST,HO-1,NQO1,and Nrf2,and decreased mRNA expression level of Keap1 in the DEL-exposed Artemia(P<0.05).Therefore,DEL is toxic to Artemia,while PHL alleviates DEL-induced oxidative damage by possibly regulating the Nrf2signaling pathway.This study provided a theoretical basis for PHL to reduce pesticide-induced toxicity in aquatic animals.

Tilapia Head Glycolipid Alleviates Indomethacin-Induced Gastric Ulcer via Regulating Oxidative Stress and Inflammation Through COX/PGE2 Signaling Pathway in Adult Rats

The aim of this experiment was to investigate the ameliorative effect and molecular mechanism of tilapia head glycolipid(TH-GL)on indomethacin(IDM)-induced gastric ulcer in male Sprague Dawley(SD)rats.The gastric ulcer model was established by oral administration of 30mgkg^(-1) IDM after 7 days of TH-GL or omeprazole(OME)administration in rats.Then the macroscopic gastric injury symptoms,gastric mucosa protective factor cyclooxygenase 1(COX-1),cyclooxygenase 2(COX-2),prostaglandin E_(2)(PGE_(2)),the levels of oxidative stress,and inflammatory cytokine expression levels in the rats were analyzed.The experimental results showed that multiple ulcers appeared on the gastric surface of the rats in the model group.Compared to the model group,TH-GL significantly alleviated gastric ulcers and reduced the gastric damage index in rats.In addition,TH-GL significantly promoted the expression of constitutive enzyme COX-1 while inhibited the expression of inducible enzyme COX-2,and make PGE2 maintain at normal levels.TH-GL also inhibited oxidative stress and inflammatory responses,increased superoxide dismutase(SOD)activity and glutathione(GSH)content,decreased the level of malondialdehyde(MDA)and the content of pro-inflammatory factor.In conclusion,these results suggested that TH-GL could maintain the expression levels of COX-1 and PGE2 while inhibit the expression of COX-2 in the gastric of rat and then prevent IDM-induced gastric ulcer,which may be related to the regulation of oxidative stress and inflammatory response.Therefore,TH-GL might be a new option for the prevention of gastric diseases induced by IDM.

Effects of dietary Clostridium butyricum and rumen protected fat on meat quality,oxidative stability,and chemical composition of finishing goats

Background Clostridium butyricum(CB)is a probiotic that can regulate intestinal microbial composition and improve meat quality.Rumen protected fat(RPF)has been shown to increase the dietary energy density and provide essential fatty acids.However,it is still unknown whether dietary supplementation with CB and RPF exerts beneficial effects on growth performance and nutritional value of goat meat.This study aimed to investigate the effects of dietary CB and RPF supplementation on growth performance,meat quality,oxidative stability,and meat nutritional value of finishing goats.Thirty-two goats(initial body weight,20.5±0.82 kg)were used in a completely randomized block design with a 2 RPF supplementation(0 vs.30 g/d)×2 CB supplementation(0 vs.1.0 g/d)factorial treatment arrangement.The experiment included a 14-d adaptation and 70-d data and sample collection period.The goats were fed a diet consisted of 400 g/kg peanut seedling and 600 g/kg corn-based concentrate(dry matter basis).Result Interaction between CB and RPF was rarely observed on the variables measured,except that shear force was reduced(P<0.05)by adding CB or RPF alone or their combination;the increased intramuscular fat(IMF)content with adding RPF was more pronounced(P<0.05)with CB than without CB addition.The pH24h(P=0.009),a*values(P=0.007),total antioxidant capacity(P=0.050),glutathione peroxidase activities(P=0.006),concentrations of 18:3(P<0.001),20:5(P=0.003)and total polyunsaturated fatty acids(P=0.048)were increased,whereas the L*values(P<0.001),shear force(P=0.050)and malondialdehyde content(P=0.044)were decreased by adding CB.Furthermore,CB supplementation increased essential amino acid(P=0.027),flavor amino acid(P=0.010)and total amino acid contents(P=0.024)as well as upregulated the expression of lipoprotein lipase(P=0.034)and peroxisome proliferator-activated receptorγ(PPARγ)(P=0.012),and downregulated the expression of stearoyl-CoA desaturase(SCD)(P=0.034).The RPF supplementation increased dry matter intake(P=0.005),averaged daily gain(trend,P=0.058),hot carcass weight(P=0.046),backfat thickness(P=0.006),concentrations of 16:0(P<0.001)and c9-18:1(P=0.002),and decreased the shear force(P<0.001),isoleucine(P=0.049)and lysine content(P=0.003)of meat.In addition,the expressions of acetyl-CoA carboxylase(P=0.003),fatty acid synthase(P=0.038),SCD(P<0.001)and PPARγ(P=0.022)were upregulated due to RPF supplementation,resulting in higher(P<0.001)content of IMF.Conclusions CB and RPF could be fed to goats for improving the growth performance,carcass traits and meat quality,and promote fat deposition by upregulating the expression of lipogenic genes of Longissimus thoracis muscle.

Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for Cath-KP.In vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant properties.Using the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway activation.Both focal adhesion kinase(FAK)and p38 were also identified as regulatory elements.In the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated dyskinesia.To the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress.These findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

Carbon-based nanomaterials cause toxicity by oxidative stress to the liver and brain in Sprague-Dawley rats

Carbon-based nanomaterials have important research significance in various disciplines,such as composite materials,nanoelectronic devices,biosensors,biological imaging,and drug delivery.Recently,the human and ecological risks associated with carbon-based nanomaterials have received increasing attention.However,the biological safety of carbon based nanomaterials has not been systematically studied.In this study,we used different types of carbon materials,namely,graphene oxide(GO),single-walled carbon nanotubes(SWCNTs),and multiwalled carbon nanotubes(MWCNTs),as models to observe their distribution and oxidative damage in vivo.The results of Histopathological and ultrastructural examinations indicated that the liver and lungs were the main accumulation targets of these nanomaterials.SR-μ-XRF analysis revealed that SWCNTs and MWCNTs might be present in the brain.This shows that the three types of carbon-based nanomaterials could cross the gas-blood barrier and eventually reach the liver tissue.In addition,SWCNTs and MWCNTs could cross the blood-brain barrier and accumulate in the cerebral cortex.The increase in ROS and MDA levels and the decrease in GSH,SOD,and CAT levels indicated that the three types of nanomaterials might cause oxidative stress in the liver.This suggests that direct instillation of these carbon-based nanomaterials into rats could induce ROS generation.In addition,iron(Fe)contaminants in these nanomaterials were a definite source of free radicals.However,these nanomaterials did not cause obvious damage to the rat brain tissue.The deposition of selenoprotein in the rat brain was found to be related to oxidative stress and Fe deficiency.This information may support the development of secure and reasonable applications of the studied carbon-based nanomaterials.

Effect of organic mineral supplementation in reducing oxidative stress in Holstein calves during short‑term heat stress and recovery conditions

Background This study investigated the effects of inorganic and organic minerals on physiological responses,oxidative stress reduction,and rumen microbiota in Holstein bull calves(123.81±9.76 kg;5 months old)during short-term heat stress(HS)and recovery periods.Eight Holstein calves were randomly assigned to four treatment groups:no mineral supplementation(Con),inorganic minerals(IM),organic minerals(OM),and high-concentration organic minerals(HOM)and two thermal environments(HS and recovery)using 4×2 factorial arrangement in a crossover design of four periods of 35 d.Calves were maintained in a temperature-controlled barn.The experimental period consisted of 14 d of HS,14 d of recovery condititon,and a 7-d washing period.Results Body temperature and respiration rate were higher in HS than in the recovery conditions(P<0.05).Selenium concentration in serum was high in the HOM-supplemented calves in both HS(90.38μg/dL)and recovery periods(102.00μg/dL)(P<0.05).During the HS period,the serum cortisol was 20.26 ng/mL in the HOM group,which was 5.60 ng/mL lower than in the control group(P<0.05).The total antioxidant status was the highest in the OM group(2.71 mmol Trolox equivalent/L),followed by the HOM group during HS,whereas it was highest in the HOM group(2.58 mmol Trolox equivalent/L)during the recovery period(P<0.05).Plasma malondialdehyde and HSP70 levels were decreased by HOM supplementation during the HS and recovery periods,whereas SOD and GPX levels were not significantly affected(P>0.05).The principal coordinate analysis represented that the overall rumen microbiota was not influenced by mineral supplementation;however,temperature-induced microbial structure shifts were indicated(PERMANOVA:P<0.05).At the phylum level,Firmicutes and Actinobacteria decreased,whereas Fibrobacteres,Spirochaetes,and Tenericutes increased(P<0.05),under HS conditions.The genus Treponema increased under HS conditions,while Christensenella was higher in recovery conditions(P<0.05).Conclusion HOM supplementation during HS reduced cortisol concentrations and increased total antioxidant status in Holstein bull calves,suggesting that high organic mineral supplementation may alleviate the adverse effects of HS.

Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.

Thrombopoietin ameliorates doxorubicin-induced toxicities in H9c2 myocardiocytes by inhibiting oxidative stress through the SIRT1/p38 MAPK signaling pathway

Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay.The protein expressions of SIRT1 and p38 MAPK were measured by Western blot.RT-qPCR was also used to determine SIRT1 mRNA expression.In addition,intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated.Results:Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability.It also increased SIRT1 and decreased p-p38 MAPK protein expressions.In addition,thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress,and enhanced antioxidant enzyme activities.However,silencing SIRT1 abrogated the protective effects of thrombopoietin,as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels.Conclusions:Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway.However,its protective effects need to be further verified in animal tests.

Electrochemical reduction of carbon dioxide to produce formic acid coupled with oxidative conversion of biomass

Electrochemical reduction of CO_(2)(CO_(2)RR)has become a research hot spot in recent years in the context of carbon neutrality.HCOOH is one of the most promising products obtained by electrochemical reduction of CO_(2) due to its high energy value as estimated by market price per energy unit and wide application in chemical industry.Biomass is the most abundant renewable resource in the natural world.Coupling biomass oxidative conversion with CO_(2)RR driven by renewable electricity would well achieve carbon negativity.In this work,we comprehensively reviewed the current research progress on CO_(2)RR to produce HCOOH and coupled system for conversion of biomass and its derivatives to produce value-added products.Sn-and Bi-based electrocatalysts are discussed for CO_(2)RR with regards to the structure of the catalyst and reaction mechanisms.Electro-oxidation reactions of biomass derived sugars,alcohols,furan aldehydes and even polymeric components of lignocellulose were reviewed as alternatives to replace oxygen evolution reaction(OER)in the conventional electrolysis process.It was recommended that to further improve the efficiency of the coupled system,future work should be focused on the development of more efficient and stable catalysts,careful design of the electrolytic cells for improving the mass transfer and development of environment-friendly processes for recovering the formed formate and biomass oxidation products.

Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

Objective:To explore the effect of black radish(Raphanus sativus L.var niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced hepatotoxicity.Methods:Thirty-two mice were divided into four groups:the control group received drinking water by gavage,the second group was administered with 100 mg/kg of sodium valproate,the third group received 300 mg/kg of black radish root extract,and the fourth group was given both sodium valproate(100 mg/kg)and black radish root extract(300 mg/kg).After 28 days,the mice were euthanized,and serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP),along with liver malondialdehyde(MDA),reactive oxygen species(ROS),mitochondrial parameters,tumor necrosis factor-alpha(TNF-α)gene expression,and histopathological changes were assessed.Results:Sodium valproate caused hepatic damage in mice,characterized by elevated serum levels of liver enzymes,increased MDA and ROS levels and TNF-αgene expression,as well as histopathological alterations.The black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST,MDA,ROS,TNF-αgene expression,as well as mitochondrial impairment,but did not have a significant effect on sodium valproate-induced histopathological changes.Conclusions:The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury,possibly through mitigating oxidative stress,mitochondrial impairment,and inflammatory mediator expression.

Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.

Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway

BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway.This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats.The serum metabolites,β-leucine(β-Leu)and traumatic acid,were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1.CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway,modulating gut microbiota and serum metabolites.β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.

Crosstalk among Oxidative Stress,Autophagy,and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells:A Mixed Computational and Experimental Study

Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.

Ethyl acetate fraction of Sargassum pallidum extract attenuates particulate matter-induced oxidative stress and inflammation in keratinocytes and zebrafish

Objective:To evaluate the effect of the ethyl acetate fraction derived from Sargassum pallidum extract against particulate matter(PM)-induced oxidative stress and inflammation in HaCaT cells and zebrafish.Methods:HaCaT cells and zebrafish were used to evaluate the protective effects of the ethyl acetate fraction of Sargassum pallidum extract against PM-induced oxidative stress and inflammation.The production of nitric oxide(NO),intracellular ROS,prostaglandin E_(2)(PGE_(2)),and pro-inflammatory cytokines,and the expression levels of COX-2,iNOS,and NF-κB were evaluated in PM-induced HaCaT cells.Furthermore,the levels of ROS,NO,and lipid peroxidation were assessed in the PM-exposed zebrafish model.Results:The ethyl acetate fraction of Sargassum pallidum extract significantly decreased the production of NO,intracellular ROS,and PGE_(2) in PM-induced HaCaT cells.In addition,the fraction markedly suppressed the levels of pro-inflammatory cytokines and inhibited the expression levels of COX-2,iNOS,and NF-κB.Furthermore,it displayed remarkable protective effects against PM-induced inflammatory response and oxidative stress,represented by the reduction of NO,ROS,and lipid peroxidation in zebrafish.Conclusions:The ethyl acetate fraction of Sargassum pallidum extract exhibits a protective effect against PM-induced oxidative stress and inflammation both in vitro and in vivo and has the potential as a candidate for the development of pharmaceutical and cosmeceutical products.

Structural characterization of three acidic polysaccharides from Opuntia dillenii Haw.fruits and their protective effect against hydrogen peroxide-induced oxidative stress in Huh-7 cells

Three novel acidic polysaccharide fractions(OFPP-1,OFPP-2,OFPP-3)with different m olecular weights(803.7,555.1 and 414.5 k Da)were isolated from the peeled Opuntia dillenii Haw.fruits by alkali-extraction,graded alcohol precipitation and column chromatography.Structural analysis indicated that OFPPs were pectic polysaccharides consisting of rhamnose,arabinose and galactose residues.The backbone of OFPP-1 consisted of a repeating unit→6-α-D-Galp A-(1→2)-α-L-Rhap-(1→with T-α-D-Galp A-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→,T-β-D-Xylp-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→or T-α-D-Galp A-(1→3)-α-L-Araf-(1→as the side chains.The backbone of OFPP-2 consisted of a disaccharide repeating unit→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→with T-β-L-Araf-(1→as the branches substituted at the O-4 position of→2,4)-α-LRhap-(1→.Whereas the backbone of OFPP-3 was→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-β-L-Araf-(1→or→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→,which was branched at the O-4 position of→2,4)-α-L-Rhap-(1→.Moreover,these three polysaccharide fractions could protect Huh-7 cells against H2O2-induced oxidative stress to different extents by decreasing the MDA content and increasing the SOD,CAT,GSH-Px activities and the GSH level in the Huh-7 cells.These results suggest that OFPPs have the potential to be used as natural antioxidants.