Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mech...Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.展开更多
This study aimed to investigate the antioxidant effect of soybean milk fermented by a new type of Lactobacillus fermentum(LF-HFY02)by using D-galactose induced aging mice model.Firstly,the optimal fermentation conditi...This study aimed to investigate the antioxidant effect of soybean milk fermented by a new type of Lactobacillus fermentum(LF-HFY02)by using D-galactose induced aging mice model.Firstly,the optimal fermentation conditions was screened out by detecting the effects of different fermentation temperature and time on the active components and antioxidant activity of soybean milk in viro.And then unfermented soybean milk and the soybean milk fermented by different Lactobacillus was given by gavage to D-galactose-induced aging mouse.The activities of GSH,GSH-Px,SOD,CAT and T-AOC in serum,brain and liver of soybean milk fermented by LF-HFY02 were significantly increased,while the content of MDA and the level of AGEs in hippocampal were significantly decreased compared with D-galactose induced group.Further more,the mRNA expression of GSH and SOD in mouse liver were obviously up-regulated by soybean milk fermented by LF-HFY02.The skin tissue structure of mice in the LF-HFY02 fermented soybean milk group was more complete,the collagen fibers were increased and arranged orderly and liver inflammation has improved compared with the model group.And Western blot analysis showed that LF-HFY02 effectively upregulated EGFR,SOD and GSH protein expression in mouse liver.These findings suggest that LF-HFY02 can effectively prevent D-galactose-induced oxidation and aging in mice,and the effect was even better than that of the Lactobacillus delbruechii subsp.bulgaricus and vitamin C.Thus,LF-HFY02 may be potentially employed as a probiotic strain.In conclusion,soybean milk fermented by LF-HFY02 can increase the content of antioxidant factors and the activity of antioxidant enzymes by regulating gene and protein expression,and finally inhibit the process of tissue cell peroxidation,and improve the oxidative damage of mouse skin and liver.The results could provide a basis for the research and development and industrial production of probiotic-related fermented soybean milk products.展开更多
Neurocognitive dysfunction is a common postoperative complication,especially in older adult patients.Fingolimod(FTY720)is a sphingosine-1-phosphate receptor modulator that has been found to be neuroprotective in sever...Neurocognitive dysfunction is a common postoperative complication,especially in older adult patients.Fingolimod(FTY720)is a sphingosine-1-phosphate receptor modulator that has been found to be neuroprotective in several animal models of central nervous system disease.However,few reports have examined whether FTY720 could mitigate postoperative cognitive dysfunction.In this study,we investigated whether FTY720 could prevent postoperative neurocognitive impairment in mice subjected to D-galactose-induced aging.We induced an accelerated model of aging by administering an intraperitoneal injection of D-galactose.Subsequently,we performed a partial hepatolobectomy under sevoflurane anesthesia.FTY720(1 mg/kg)was administered intraperitoneally 3 hours before and 24 hours after anesthesia and surgery.Our results indicated that anesthesia and surgery significantly impaired spatial memory in the Y-maze test 6 hours after surgery.We also found that problem solving ability and long-term memory in the puzzle box test on postoperative days 2–4 were significantly improved by FTY720 treatment.Immunohistochemical staining and western blot assay demonstrated that FTY720 significantly inhibited microglial activation in the hippocampal CA1 region of mice 6 hours and 3 days after anesthesia,and down-regulated the expression of synaptic-related proteins postsynaptic density protein 95 and GluR2 in the hippocampus.These results indicate that FTY720 improved postoperative neurocognitive dysfunction in mice subjected to D-galactose-induced aging.This study was approved by the Experimental Animal Ethics Committee of the Third Xiangya Hospital of Central South University of China(approval No.LLSC(LA)2016-025)on September 27,2016.展开更多
Mitochondrial DNA(mtDNA) common deletion(CD) plays a significant role in aging and age-related diseases.In this study,we used D-galactose(D-gal) to generate an animal model of aging and the involvement and causative m...Mitochondrial DNA(mtDNA) common deletion(CD) plays a significant role in aging and age-related diseases.In this study,we used D-galactose(D-gal) to generate an animal model of aging and the involvement and causative mechanisms of mitochondrial damage in such a model were investigated.Twenty 5-week-old male Sprague-Dawley rats were randomly divided into two groups:D-gal group(n=10) and control group(n=10).The quantity of the mtDNA CD in the hippocampus was determined using a TaqMan real-time PCR assay.Transmission electron microscopy was used to observe the mitochondrial ultrastructure in the hippocampus.Western blot was used to detect the protein levels of NADPH oxidase(NOX) and uncoupling protein 2(UCP2).We found that the level of mtDNA CD was significantly higher in the hippocampus of D-gal-induced aging rats than in control rats.In comparison with the control group,the mitochondrial ultrastructure in the hippocampus of D-gal-treated rats was damaged,and the protein levels of NOX and UCP2 were significantly increased in the hippocampus of D-gal-induced aging rats.This study demonstrated that the levels of mtDNA CD and NOX protein expression were significantly increased in the hippocampus of D-gal-induced aging rats.These findings indicate that NOX-dependent reactive oxygen species generation may contribute to D-gal-induced mitochondrial damage.展开更多
Aim:To explore the influence of different doses of D-galactose on learning memory capacity in mice.Methods:The 2-month-old KM mice were randomly divided into D-galactose-treated groups (75,100,150,300 mg·kg^-1) a...Aim:To explore the influence of different doses of D-galactose on learning memory capacity in mice.Methods:The 2-month-old KM mice were randomly divided into D-galactose-treated groups (75,100,150,300 mg·kg^-1) and normal control group,with 12 mice in each group.The corresponding dose of D-galactose was administered subcutaneously to the back of the neck,and normal control group was injected subcutaneously with saline for 8 weeks.Learning memory capacity of mice was detected through Morris water maze,step-down passive avoidance test and new object recognition test.Meanwhile,the enzymatic indicators in the brain were determined to detect the damage degree in mice with different doses of D-galactose.Results:Compared with the normal control group,the spatial and non-spatial cognitive functions and brain enzyme levels of D-galactose in each dose group was damaged to varying degrees,especially the dose of 100 mg·kg-1 group.In the water maze experiment,D-galactose groups significantly prolonged the time of crossing the platform for the first time and decreased the number of crossing platforms,especially at the dose of 100 mg·kg-1 (P < 0.05);in the new object recognition experiment,discrimination index was significantly decreased in each D-galactose group (P < 0.01),and the dose of 100 mg·kg-1 was most obvious;in addition,D-galactose could significantly increase the level of acetylcholinesterase (AChE)(P < 0.01),decrease the levels of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px),and total antioxidant capacity (T-AOC)(P < 0.05 or P < 0.01) in the mice brain.Conclusion:Subcutaneous injection of low-medium-high dose of D-galactose for 8 weeks in the back of the neck can cause changes in brain parameters in mice,but the effects of different doses of D-galactose on some indicators are significantly different.D-galactose model is effective and stable at the dose of 100 mg·kg-1.展开更多
Background:The prevalence of premature ovarian insufficiency(POI)is gradually increasing,safer and more effective treatments are urgently needed.Objective:The aim of this study was to evaluate the effects of Ningxin-Y...Background:The prevalence of premature ovarian insufficiency(POI)is gradually increasing,safer and more effective treatments are urgently needed.Objective:The aim of this study was to evaluate the effects of Ningxin-Yishen formula(NXYSF)on D-galactose-induced POI mice as well as to shed a light on its potential mechanisms.Methods:Six to eight weeks old female C57BL/6 mice were used in this study and randomly divided into six groups:control group;model group;estradiol valerate(EV)treatment group and NXYSF treatment group with graded doses(9.5,19,and 38 g·kg^(−1)/d).Both EV and NXYSF treatments were initiated at the 15th day of modeling and lasted for 28 days.Afterwards,the ovarian function was evaluated in each group by analyzing the proportion of primordial follicles as well as the serum sex hormone levels.Furthermore,network pharmacology approach was performed to elucidate the potential targets of NXYSF,which was verified through western blotting experiments finally.Results:NXYSF could significantly reverse the inefficiency of weight gain caused by POI,and promote the devel-opment of primordial follicles.In addition,it could restore the abnormal serum anti-Müllerian hormone(AMH),estradiol(E 2),luteinizing hormone(LH)and follicle-stimulating hormone(FSH).Moreover,some crucial key gene targets including TP53 were as propose to be relate with the effect of NXYSF through network pharmacology anal-ysis.Last but importantly,western blotting experiments confirmed that NXYSF could inhibit the expression of p53 protein in mouse ovaries.展开更多
Wheat embryo globulin(WEG)has been proven to possess multiple biological activities,including antioxidative properties,immunomodulatory,and so on.Aged mouse model were established by subcutaneous injection of D-galact...Wheat embryo globulin(WEG)has been proven to possess multiple biological activities,including antioxidative properties,immunomodulatory,and so on.Aged mouse model were established by subcutaneous injection of D-galactose(D-gal),and the effects of WEG on learning,memory,and antioxidant capacity in aging mice were explored through behavioural tests and antioxidant enzyme activities determination.Compared with the Model group,WEG improved the percentage of the platform quadrant,increased the number of crossing platforms,and enhanced the identification indexs.WEG also increased total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)activities in the liver and brains of aging mice,and reduced malondialdehyde(MDA)content.Pathological observations indicated that WEG protected against damage to brain in D-gal-induced aging mice.These results effectively revealed that WEG not only improved the abilities of learning and memory,and the cognitive impairment,but also delayed the aging process of the D-gal-induced mice.展开更多
Obejective:To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells.Methods:SH-SY5Y cells were randomly divided into control(D-galactose 0 mmol/L group),D-galactose(25...Obejective:To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells.Methods:SH-SY5Y cells were randomly divided into control(D-galactose 0 mmol/L group),D-galactose(25 mmol/L,50 mmol/L,100 mmol/L,200 mmol/L,400 mmol/L)groups,and treated with corresponding concentrations of D-galactose for 48 h.The changes of cell morphology,β-galactosidase,the cell morphology,β-galactosidase activity by microscopic observation,cell proliferation rate by EdU kit and cell survival rate by CCK-8 assay were used to determine the decaying concentration of D-galactose and to establish the senescence model.The senescent SH-SY5Y cells were randomly divided into control group(oxygen glucose deprivation without treatment group),oxygen glucose deprivation treatment(0.5 h,1 h,1.5 h,2 h)group,followed by re-glucose reoxygenation for 24 h,and CCK-8 assay for the survival rate of senescent SH-SY5Y cells.Results:There were no significant changes in cell morphology and β-gal activity in the 25 mmol/L and 50 mmol/L groups compared with the control group(P>0.05),cytosolic hypertrophy was seen in the cells of the 100 mmol/L group,chromatin fixation in the cells of the 200 mmol/L group,and massive vacuolization in the cells of the 400 mmol/L group;the positive rate ofβ-galactosidase staining in the cells of the(100-400 mmol/L)group was significantly higher compared with the control group(P<0.05),with little difference between the 100 mmol/L and 200 mmol/L groups(P>0.05);the cell proliferation ability of the(100-400 mmol/L)group was significantly decreased in a concentration-dependent manner(P<0.05);the cell survival rate was decreased in a concentration-dependent manner(P<0.05),with IC_(50) between 100 mmol/L and 200 mmol/L.The survival of senescent SH-SY5Y cells showed a time-dependent decrease in oxygen-glucose deprivation(P<0.05),with an IC_(50) close to 1 h.Conclusion:D-gal concentration of 100 mmoL/L and 48 h of cell action could establish a survival rate of about 50%of senescent SH-SY5Y cells,and oxygen glucose deprivation of senescent SH-SY5Y cells for 1 h and reperfusion for 24 h could establish an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells with a survival rate close to 50%.展开更多
The protective roles of α-lipoic acid in the rat model of mitochondrial DNA (mtDNA) 4834bp deletion in inner ear were investigated. Forty female Wistar rats at 4 weeks of age were divided into four groups: group A (D...The protective roles of α-lipoic acid in the rat model of mitochondrial DNA (mtDNA) 4834bp deletion in inner ear were investigated. Forty female Wistar rats at 4 weeks of age were divided into four groups: group A (D-galactose group, n=10), group B (D-galactose+α-lipoic acid group, n=10), group C (α-lipoic acid group, n=10), and group D (control group, n=10). Auditory brainstem response (ABR) was used to detect the hearing threshold. Colorimetry was used to analyze activity of superoxide dismutase (SOD) and concentration of malondialdehyde (MDA). The percentage of mtDNA4834bp deletion in inner ear was identified by real-time PCR. There was no significant difference in ABR threshold shift among all groups. The percentage of mtDNA4834bp deletion in group A was higher than that in other groups, but there was no significant difference in percentage of mtDNA4834bp deletion among groups B, C, and D. The activity of SOD in group A was lower than that in other groups. The concentration of MDA in group A was higher than that in other groups. It was concluded that there was no significant hearing loss when the percentage of mtDNA4834bp deletion was lower than 12.5%. α-Lipoic acid could prevent the reactive oxygen species (ROS)-induced mtDNA4834bp deletion in inner ear of rats.展开更多
BACKGROUND:Prophylactic dietary restriction(DR),whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents.However,whether the anti-aging and neuroprotective efficac...BACKGROUND:Prophylactic dietary restriction(DR),whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents.However,whether the anti-aging and neuroprotective efficacy of DR initiate late in life or accompany the aging process remains unclear.OBJECTIVE:The present study sought to:(1) determine if DR could protect against behavioral decline in mice when implemented during the aging process induced by D-galactose and(2) examine neuronal apoptosis in these aged brains and whether DR could block apoptosis.DESIGN,TIME AND SETTING:The randomized controlled animal study.The experiment was performed at the Experimental Animal Center of Capital Medical University and the Laboratory Center of School of Public Health of Captial Medical University of China from April 2006 to October 2007.MATERIALS:D-galactose(D-gal) was purchased from Beijing Chemical-Regent Company(Beijing,China).Terminal transferase dUTP nick end labeling(TUNEL) detection kit was obtained from Roche,Germany.Assay kits for antioxidant enzyme activities and malondialdehyde contents were purchased from Jiancheng Institute of Biotechnology(Nanjing,China).Morris water maze(Friends Honesty Life Sciences Co.Ltd.,Hong Kong,China) and Flow Cytometry(Coulter,USA) were used in this study.METHODS:A total of 40 male Institute of Cancer Research(ICR) mice,3 months old,were equally and randomly divided into D-gal treatment,DR treatment,D-gal + DR treatment and normal control groups,and were then randomly assigned to one of two feeding regimens:ad libitum access to food or DR which received a 70% amount of daily food intake as that by ad libitum fed mice.There were two replicates per feeding regimen and mice were fed for 10 weeks,with or without a daily subcutaneous injection of D-gal at 100 mg/kg.MAIN OUTCOME MEASURES:Animals' spatial learning and memory performance were tested in the Morris water maze.Neuronal apoptosis rates were evaluated by Annexin V/flow cytometry assay and TUNEL assay.Lipid peroxidation levels and antioxidant defense capacity of the brain were measured using testing kits.RESULTS:DR markedly reduced the prolonged escape latency of D-gal mice in the water maze test(P < 0.01).Annexin V and TUNEL assays showed that the D-gal mice had a significant higher percentage of neuronal apoptosis compared with normal control mice(P < 0.05),and that DR treatment markedly decreased this apoptotic cell death(P < 0.05).DR also reversed the decline of total superoxide dismutase and glutathione peroxidase activities and the increase of malondialdehyde levels in the brain of D-gal mice(P < 0.05,respectively).CONCLUSION:DR reduces the impact of D-gal-induced brain aging in mice and can reverse performance decline and neurobiochemical impairments.These results demonstrate that implementation of DR in conditions of chronic oxidative stress can be neuroprotective,and that senium DR can be beneficial for healthy aging.展开更多
External electric field of 0.001, 0.01 and 0.05 a.u. changes distribution of the electron density in α- and β-D-glucose, α- and β-D-galactose, α- and β-fructopyranoses and α- and β-fructofuranoses, α- and β-...External electric field of 0.001, 0.01 and 0.05 a.u. changes distribution of the electron density in α- and β-D-glucose, α- and β-D-galactose, α- and β-fructopyranoses and α- and β-fructofuranoses, α- and β-D-ribofuranoses and α and β-D-xylo- furanoses. Hyper-Chem 8.0 software was used together with the AM1 method for optimization of the conformation of the molecules of monosaccharides under study. Then polarizability, charge distribution, potential and dipole moment for molecules placed in the external electric field of 0.000, 0.001, 0.01 and 0.05 a.u. were calculated involving DFT 3-21G method. Application of the external field induced polarizability of electrons, atoms and dipoles, the latter resulting in eventual reorientation of the molecules along the applied field of the molecules and the electron density redistribution at particular atoms. Increase in the field strength generated mostly irregular changes of the electron densities at particular atoms of the molecules as well as polarizabilities. Energy of these molecules and their dipole moments also varied with the strength of the field applied. Results of computations imply that saccharides present in the living organisms may participate in the response of the living organisms to the external electric field affecting metabolism of the molecules in the body fluids by fitting molecules to the enzymes. Structural changes of saccharide components of the membranes can influence the membrane permeability.展开更多
[Objectives] To study the effect of PPARγ agonist DA on the cognitive function of AD mice as well as the mechanism.[Methods]50 Kunming male mice were randomly divided into normal control group,model group and decanoi...[Objectives] To study the effect of PPARγ agonist DA on the cognitive function of AD mice as well as the mechanism.[Methods]50 Kunming male mice were randomly divided into normal control group,model group and decanoic acid administration group,the AD mice model was established by subcutaneous injection of D-galactose for 8 weeks,and the treatment group was administered orally with different doses of decanoic acid( low dose of 50 mg/kg,middle dose of 100 mg/kg,high dose of 200 mg/kg). After 8 weeks,the Morris water maze was used to detect the learning and memory capability of mice; HE staining was used to observe the morphological change of hippocampal cells in brain tissue; Western-blot and immunohistochemistry technique were used to detect the expression of PPARγ and Aβ42 protein in brain tissue; the ELISA method was used for the determination of TNF-α and i NOS level in serum. [Results]Morris water maze results showed that DA could significantly improve the learning and memory function in AD mice( P < 0. 05); HE staining showed that DA could significantly reduce degeneration in hippocampal cells; Western-blot and immunohistochemistry results showed that DA could promote the expression of PPARγ and reduce the expression of Aβ42 in brain tissue( P < 0. 05); ELISA results showed that the TNF-α,i NOS levels decreased in AD mice serum after DA treatment( P < 0. 05). [Conclusions] DA could significantly improve the cognitive function of AD mice,improve the degeneration of hippocampal cells in brain tissue,and decrease the expression of Aβ42 in brain tissue. The mechanism might be related to activation of PPARγ protein and down-regulation of expression of relevant inflammatory factors.展开更多
Objective:This study explored the myocardial protection role of Jujuboside A through an ischemia–hypoxia–reperfusion(IHR)model.Materials and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish ...Objective:This study explored the myocardial protection role of Jujuboside A through an ischemia–hypoxia–reperfusion(IHR)model.Materials and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish an aging and IHR model.There are four groups of experiments:Control,IHR,D-gal+IHR,and D-gal+IHR+Jujuboside A.Cells viability,Adenosine triphosphate(ATP),reactive oxygen species(ROS),nicotinamide adenine dinucleotide(NAD+),nicotinamide adenine dinucleotide hydride(NADH)content,and NAD+/NADH ratio were detected using biochemical methods.Inflammatory cytokines level was detected by enzyme-linked immunosorbent assay.The expression of CD38,Recombinant NLR Family,pyrin domain-containing protein 3(NLRP3),and silent mating type information regulation 2homolog 3(SIRT3)protein was detected by Western blotting.Results:Compared to the IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and SIRT3 protein expression decreased,ROS level and inflammatory cytokines increased,and CD38 and NLRP3 proteins raised in the D-gal+IHR group.Compared to the D-gal+IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and expression of SIRT3 protein increased,ROS level and inflammatory cytokines level decreased,and expression of the CD38 and NLRP3proteins decreased in the D-gal+IHR+Jujuboside A group.Conclusions:Jujuboside A inhibited the expression of CD38,improved energy metabolism disorder,and mitochondrial function,and decreased inflammation in D-gal-induced H9c2 cells.展开更多
Objective: To observe the effects of Cistanche desertica polysaccharides (CDP) on the learning and memory functions and cerebral ultrastructure in experimental aging mice. Methods: CDP was administrated intragastrical...Objective: To observe the effects of Cistanche desertica polysaccharides (CDP) on the learning and memory functions and cerebral ultrastructure in experimental aging mice. Methods: CDP was administrated intragastrically 50 or 100 mg/kg per day for 64 successive days to experimental aging model mice induced by D￣galactose, then the learning and memory functions of mice were estimated by step￣down test and Y￣maze test; organelles of brain tissue and cerebral ultrastructure were observed by transmission electron microscope and physical strength was determined by swimming test. Results: CDP could obviously enhance the learning and memory functions ( P <0.01) and prolong the swimming time ( P <0.05), decrease the number of lipofuscin and slow down the degeneration of mitochondria in neurons( P <0.05), and improve the degeneration of cerebral ultra￣structure in aging mice. Conclusion: CDP could improve the impaired physiological function and alleviate cerebral morphological change in experimental aging mice.展开更多
基金supported by the National Science Fund for Distinguished Young Scholars(32025029)the Shanghai Education Committee Scientific Research Innovation Projects(2101070007800120)+1 种基金the Yili Health Science Foundation of Chinese Institute of Food Science and Technology(2021-Y06)the Shanghai Engineering Research Center of food microbiology program(19DZ2281100)。
文摘Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.
基金funded by Chongqing University Innovation Research Group Project(CXQTP20033)the Science and Technology Project of Chongqing(cstc2021jcyj-msxm X0408)Scientific and Technological Innovation Project of Construction of Double City Economic Circle in Chengdu-Chongqing Area of Chongqing Education Commission(KJCX2020052)。
文摘This study aimed to investigate the antioxidant effect of soybean milk fermented by a new type of Lactobacillus fermentum(LF-HFY02)by using D-galactose induced aging mice model.Firstly,the optimal fermentation conditions was screened out by detecting the effects of different fermentation temperature and time on the active components and antioxidant activity of soybean milk in viro.And then unfermented soybean milk and the soybean milk fermented by different Lactobacillus was given by gavage to D-galactose-induced aging mouse.The activities of GSH,GSH-Px,SOD,CAT and T-AOC in serum,brain and liver of soybean milk fermented by LF-HFY02 were significantly increased,while the content of MDA and the level of AGEs in hippocampal were significantly decreased compared with D-galactose induced group.Further more,the mRNA expression of GSH and SOD in mouse liver were obviously up-regulated by soybean milk fermented by LF-HFY02.The skin tissue structure of mice in the LF-HFY02 fermented soybean milk group was more complete,the collagen fibers were increased and arranged orderly and liver inflammation has improved compared with the model group.And Western blot analysis showed that LF-HFY02 effectively upregulated EGFR,SOD and GSH protein expression in mouse liver.These findings suggest that LF-HFY02 can effectively prevent D-galactose-induced oxidation and aging in mice,and the effect was even better than that of the Lactobacillus delbruechii subsp.bulgaricus and vitamin C.Thus,LF-HFY02 may be potentially employed as a probiotic strain.In conclusion,soybean milk fermented by LF-HFY02 can increase the content of antioxidant factors and the activity of antioxidant enzymes by regulating gene and protein expression,and finally inhibit the process of tissue cell peroxidation,and improve the oxidative damage of mouse skin and liver.The results could provide a basis for the research and development and industrial production of probiotic-related fermented soybean milk products.
基金supported by the National Natural Science Foundation of China,No.81500932(YW)
文摘Neurocognitive dysfunction is a common postoperative complication,especially in older adult patients.Fingolimod(FTY720)is a sphingosine-1-phosphate receptor modulator that has been found to be neuroprotective in several animal models of central nervous system disease.However,few reports have examined whether FTY720 could mitigate postoperative cognitive dysfunction.In this study,we investigated whether FTY720 could prevent postoperative neurocognitive impairment in mice subjected to D-galactose-induced aging.We induced an accelerated model of aging by administering an intraperitoneal injection of D-galactose.Subsequently,we performed a partial hepatolobectomy under sevoflurane anesthesia.FTY720(1 mg/kg)was administered intraperitoneally 3 hours before and 24 hours after anesthesia and surgery.Our results indicated that anesthesia and surgery significantly impaired spatial memory in the Y-maze test 6 hours after surgery.We also found that problem solving ability and long-term memory in the puzzle box test on postoperative days 2–4 were significantly improved by FTY720 treatment.Immunohistochemical staining and western blot assay demonstrated that FTY720 significantly inhibited microglial activation in the hippocampal CA1 region of mice 6 hours and 3 days after anesthesia,and down-regulated the expression of synaptic-related proteins postsynaptic density protein 95 and GluR2 in the hippocampus.These results indicate that FTY720 improved postoperative neurocognitive dysfunction in mice subjected to D-galactose-induced aging.This study was approved by the Experimental Animal Ethics Committee of the Third Xiangya Hospital of Central South University of China(approval No.LLSC(LA)2016-025)on September 27,2016.
基金supported by grants from the Natural Science Foundation of Hubei province (No. 2010CDB08005)the National Natural Science Foundation of China (No. 30730094 and81000409)Special Funds for State Key Development Program for Basic Research of China (973 Program) (No.2011CB504504)
文摘Mitochondrial DNA(mtDNA) common deletion(CD) plays a significant role in aging and age-related diseases.In this study,we used D-galactose(D-gal) to generate an animal model of aging and the involvement and causative mechanisms of mitochondrial damage in such a model were investigated.Twenty 5-week-old male Sprague-Dawley rats were randomly divided into two groups:D-gal group(n=10) and control group(n=10).The quantity of the mtDNA CD in the hippocampus was determined using a TaqMan real-time PCR assay.Transmission electron microscopy was used to observe the mitochondrial ultrastructure in the hippocampus.Western blot was used to detect the protein levels of NADPH oxidase(NOX) and uncoupling protein 2(UCP2).We found that the level of mtDNA CD was significantly higher in the hippocampus of D-gal-induced aging rats than in control rats.In comparison with the control group,the mitochondrial ultrastructure in the hippocampus of D-gal-treated rats was damaged,and the protein levels of NOX and UCP2 were significantly increased in the hippocampus of D-gal-induced aging rats.This study demonstrated that the levels of mtDNA CD and NOX protein expression were significantly increased in the hippocampus of D-gal-induced aging rats.These findings indicate that NOX-dependent reactive oxygen species generation may contribute to D-gal-induced mitochondrial damage.
基金supported by grants from the National Natural Science Foundation of China (No 81473586,No 81202192).
文摘Aim:To explore the influence of different doses of D-galactose on learning memory capacity in mice.Methods:The 2-month-old KM mice were randomly divided into D-galactose-treated groups (75,100,150,300 mg·kg^-1) and normal control group,with 12 mice in each group.The corresponding dose of D-galactose was administered subcutaneously to the back of the neck,and normal control group was injected subcutaneously with saline for 8 weeks.Learning memory capacity of mice was detected through Morris water maze,step-down passive avoidance test and new object recognition test.Meanwhile,the enzymatic indicators in the brain were determined to detect the damage degree in mice with different doses of D-galactose.Results:Compared with the normal control group,the spatial and non-spatial cognitive functions and brain enzyme levels of D-galactose in each dose group was damaged to varying degrees,especially the dose of 100 mg·kg-1 group.In the water maze experiment,D-galactose groups significantly prolonged the time of crossing the platform for the first time and decreased the number of crossing platforms,especially at the dose of 100 mg·kg-1 (P < 0.05);in the new object recognition experiment,discrimination index was significantly decreased in each D-galactose group (P < 0.01),and the dose of 100 mg·kg-1 was most obvious;in addition,D-galactose could significantly increase the level of acetylcholinesterase (AChE)(P < 0.01),decrease the levels of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px),and total antioxidant capacity (T-AOC)(P < 0.05 or P < 0.01) in the mice brain.Conclusion:Subcutaneous injection of low-medium-high dose of D-galactose for 8 weeks in the back of the neck can cause changes in brain parameters in mice,but the effects of different doses of D-galactose on some indicators are significantly different.D-galactose model is effective and stable at the dose of 100 mg·kg-1.
基金This work was financially supported by Postgraduate Scientific Re-search Foundation of Zhejiang Chinese Medical University[Number:2020YKJ12].
文摘Background:The prevalence of premature ovarian insufficiency(POI)is gradually increasing,safer and more effective treatments are urgently needed.Objective:The aim of this study was to evaluate the effects of Ningxin-Yishen formula(NXYSF)on D-galactose-induced POI mice as well as to shed a light on its potential mechanisms.Methods:Six to eight weeks old female C57BL/6 mice were used in this study and randomly divided into six groups:control group;model group;estradiol valerate(EV)treatment group and NXYSF treatment group with graded doses(9.5,19,and 38 g·kg^(−1)/d).Both EV and NXYSF treatments were initiated at the 15th day of modeling and lasted for 28 days.Afterwards,the ovarian function was evaluated in each group by analyzing the proportion of primordial follicles as well as the serum sex hormone levels.Furthermore,network pharmacology approach was performed to elucidate the potential targets of NXYSF,which was verified through western blotting experiments finally.Results:NXYSF could significantly reverse the inefficiency of weight gain caused by POI,and promote the devel-opment of primordial follicles.In addition,it could restore the abnormal serum anti-Müllerian hormone(AMH),estradiol(E 2),luteinizing hormone(LH)and follicle-stimulating hormone(FSH).Moreover,some crucial key gene targets including TP53 were as propose to be relate with the effect of NXYSF through network pharmacology anal-ysis.Last but importantly,western blotting experiments confirmed that NXYSF could inhibit the expression of p53 protein in mouse ovaries.
基金funded by Zhongyuan Scholars in Henan Province(192101510004)Major Science and Technology Projects for Public Welfare of Henan Province(201300110300)+2 种基金Innovation Demonstration Special Project of Henan Province(201111110100)financially supported by Key Project Foundation of Natural Science Research of Universities of Henan Province in China(20A550004)Fundamental Research Funds for the Henan Provincial Colleges and Universities in Henan University of Technology(HAUT)and High-Level Talents Research Fund of HAUT(2018QNJH13,and 2018BS012)。
文摘Wheat embryo globulin(WEG)has been proven to possess multiple biological activities,including antioxidative properties,immunomodulatory,and so on.Aged mouse model were established by subcutaneous injection of D-galactose(D-gal),and the effects of WEG on learning,memory,and antioxidant capacity in aging mice were explored through behavioural tests and antioxidant enzyme activities determination.Compared with the Model group,WEG improved the percentage of the platform quadrant,increased the number of crossing platforms,and enhanced the identification indexs.WEG also increased total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)activities in the liver and brains of aging mice,and reduced malondialdehyde(MDA)content.Pathological observations indicated that WEG protected against damage to brain in D-gal-induced aging mice.These results effectively revealed that WEG not only improved the abilities of learning and memory,and the cognitive impairment,but also delayed the aging process of the D-gal-induced mice.
基金This is supported by the Youth Science Foundation of Guangxi Medical University(GXMUYSF202127)。
文摘Obejective:To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells.Methods:SH-SY5Y cells were randomly divided into control(D-galactose 0 mmol/L group),D-galactose(25 mmol/L,50 mmol/L,100 mmol/L,200 mmol/L,400 mmol/L)groups,and treated with corresponding concentrations of D-galactose for 48 h.The changes of cell morphology,β-galactosidase,the cell morphology,β-galactosidase activity by microscopic observation,cell proliferation rate by EdU kit and cell survival rate by CCK-8 assay were used to determine the decaying concentration of D-galactose and to establish the senescence model.The senescent SH-SY5Y cells were randomly divided into control group(oxygen glucose deprivation without treatment group),oxygen glucose deprivation treatment(0.5 h,1 h,1.5 h,2 h)group,followed by re-glucose reoxygenation for 24 h,and CCK-8 assay for the survival rate of senescent SH-SY5Y cells.Results:There were no significant changes in cell morphology and β-gal activity in the 25 mmol/L and 50 mmol/L groups compared with the control group(P>0.05),cytosolic hypertrophy was seen in the cells of the 100 mmol/L group,chromatin fixation in the cells of the 200 mmol/L group,and massive vacuolization in the cells of the 400 mmol/L group;the positive rate ofβ-galactosidase staining in the cells of the(100-400 mmol/L)group was significantly higher compared with the control group(P<0.05),with little difference between the 100 mmol/L and 200 mmol/L groups(P>0.05);the cell proliferation ability of the(100-400 mmol/L)group was significantly decreased in a concentration-dependent manner(P<0.05);the cell survival rate was decreased in a concentration-dependent manner(P<0.05),with IC_(50) between 100 mmol/L and 200 mmol/L.The survival of senescent SH-SY5Y cells showed a time-dependent decrease in oxygen-glucose deprivation(P<0.05),with an IC_(50) close to 1 h.Conclusion:D-gal concentration of 100 mmoL/L and 48 h of cell action could establish a survival rate of about 50%of senescent SH-SY5Y cells,and oxygen glucose deprivation of senescent SH-SY5Y cells for 1 h and reperfusion for 24 h could establish an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells with a survival rate close to 50%.
基金supported by grants from the State Key Program of National Natural Science of China (No. 30730094)the National Science & Technology Pillar Program during the Eleventh Five-year Plan Period (No. 2007BAI18B13)
文摘The protective roles of α-lipoic acid in the rat model of mitochondrial DNA (mtDNA) 4834bp deletion in inner ear were investigated. Forty female Wistar rats at 4 weeks of age were divided into four groups: group A (D-galactose group, n=10), group B (D-galactose+α-lipoic acid group, n=10), group C (α-lipoic acid group, n=10), and group D (control group, n=10). Auditory brainstem response (ABR) was used to detect the hearing threshold. Colorimetry was used to analyze activity of superoxide dismutase (SOD) and concentration of malondialdehyde (MDA). The percentage of mtDNA4834bp deletion in inner ear was identified by real-time PCR. There was no significant difference in ABR threshold shift among all groups. The percentage of mtDNA4834bp deletion in group A was higher than that in other groups, but there was no significant difference in percentage of mtDNA4834bp deletion among groups B, C, and D. The activity of SOD in group A was lower than that in other groups. The concentration of MDA in group A was higher than that in other groups. It was concluded that there was no significant hearing loss when the percentage of mtDNA4834bp deletion was lower than 12.5%. α-Lipoic acid could prevent the reactive oxygen species (ROS)-induced mtDNA4834bp deletion in inner ear of rats.
文摘BACKGROUND:Prophylactic dietary restriction(DR),whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents.However,whether the anti-aging and neuroprotective efficacy of DR initiate late in life or accompany the aging process remains unclear.OBJECTIVE:The present study sought to:(1) determine if DR could protect against behavioral decline in mice when implemented during the aging process induced by D-galactose and(2) examine neuronal apoptosis in these aged brains and whether DR could block apoptosis.DESIGN,TIME AND SETTING:The randomized controlled animal study.The experiment was performed at the Experimental Animal Center of Capital Medical University and the Laboratory Center of School of Public Health of Captial Medical University of China from April 2006 to October 2007.MATERIALS:D-galactose(D-gal) was purchased from Beijing Chemical-Regent Company(Beijing,China).Terminal transferase dUTP nick end labeling(TUNEL) detection kit was obtained from Roche,Germany.Assay kits for antioxidant enzyme activities and malondialdehyde contents were purchased from Jiancheng Institute of Biotechnology(Nanjing,China).Morris water maze(Friends Honesty Life Sciences Co.Ltd.,Hong Kong,China) and Flow Cytometry(Coulter,USA) were used in this study.METHODS:A total of 40 male Institute of Cancer Research(ICR) mice,3 months old,were equally and randomly divided into D-gal treatment,DR treatment,D-gal + DR treatment and normal control groups,and were then randomly assigned to one of two feeding regimens:ad libitum access to food or DR which received a 70% amount of daily food intake as that by ad libitum fed mice.There were two replicates per feeding regimen and mice were fed for 10 weeks,with or without a daily subcutaneous injection of D-gal at 100 mg/kg.MAIN OUTCOME MEASURES:Animals' spatial learning and memory performance were tested in the Morris water maze.Neuronal apoptosis rates were evaluated by Annexin V/flow cytometry assay and TUNEL assay.Lipid peroxidation levels and antioxidant defense capacity of the brain were measured using testing kits.RESULTS:DR markedly reduced the prolonged escape latency of D-gal mice in the water maze test(P < 0.01).Annexin V and TUNEL assays showed that the D-gal mice had a significant higher percentage of neuronal apoptosis compared with normal control mice(P < 0.05),and that DR treatment markedly decreased this apoptotic cell death(P < 0.05).DR also reversed the decline of total superoxide dismutase and glutathione peroxidase activities and the increase of malondialdehyde levels in the brain of D-gal mice(P < 0.05,respectively).CONCLUSION:DR reduces the impact of D-gal-induced brain aging in mice and can reverse performance decline and neurobiochemical impairments.These results demonstrate that implementation of DR in conditions of chronic oxidative stress can be neuroprotective,and that senium DR can be beneficial for healthy aging.
文摘External electric field of 0.001, 0.01 and 0.05 a.u. changes distribution of the electron density in α- and β-D-glucose, α- and β-D-galactose, α- and β-fructopyranoses and α- and β-fructofuranoses, α- and β-D-ribofuranoses and α and β-D-xylo- furanoses. Hyper-Chem 8.0 software was used together with the AM1 method for optimization of the conformation of the molecules of monosaccharides under study. Then polarizability, charge distribution, potential and dipole moment for molecules placed in the external electric field of 0.000, 0.001, 0.01 and 0.05 a.u. were calculated involving DFT 3-21G method. Application of the external field induced polarizability of electrons, atoms and dipoles, the latter resulting in eventual reorientation of the molecules along the applied field of the molecules and the electron density redistribution at particular atoms. Increase in the field strength generated mostly irregular changes of the electron densities at particular atoms of the molecules as well as polarizabilities. Energy of these molecules and their dipole moments also varied with the strength of the field applied. Results of computations imply that saccharides present in the living organisms may participate in the response of the living organisms to the external electric field affecting metabolism of the molecules in the body fluids by fitting molecules to the enzymes. Structural changes of saccharide components of the membranes can influence the membrane permeability.
基金Supported by Guangxi Experimental Animal Resource Sharing Platform Construction Project(2060499)
文摘[Objectives] To study the effect of PPARγ agonist DA on the cognitive function of AD mice as well as the mechanism.[Methods]50 Kunming male mice were randomly divided into normal control group,model group and decanoic acid administration group,the AD mice model was established by subcutaneous injection of D-galactose for 8 weeks,and the treatment group was administered orally with different doses of decanoic acid( low dose of 50 mg/kg,middle dose of 100 mg/kg,high dose of 200 mg/kg). After 8 weeks,the Morris water maze was used to detect the learning and memory capability of mice; HE staining was used to observe the morphological change of hippocampal cells in brain tissue; Western-blot and immunohistochemistry technique were used to detect the expression of PPARγ and Aβ42 protein in brain tissue; the ELISA method was used for the determination of TNF-α and i NOS level in serum. [Results]Morris water maze results showed that DA could significantly improve the learning and memory function in AD mice( P < 0. 05); HE staining showed that DA could significantly reduce degeneration in hippocampal cells; Western-blot and immunohistochemistry results showed that DA could promote the expression of PPARγ and reduce the expression of Aβ42 in brain tissue( P < 0. 05); ELISA results showed that the TNF-α,i NOS levels decreased in AD mice serum after DA treatment( P < 0. 05). [Conclusions] DA could significantly improve the cognitive function of AD mice,improve the degeneration of hippocampal cells in brain tissue,and decrease the expression of Aβ42 in brain tissue. The mechanism might be related to activation of PPARγ protein and down-regulation of expression of relevant inflammatory factors.
基金Construction of atrial fibrillation-specific disease database(shdc2020cr6012-003)3 years action plan of Shanghai Shenkang Medical Development Center(shdc2020cr1053b)+1 种基金Science and technology support project of Shanghai Municipal Commission of Science and Technology(18401932800)Shanghai Shenkang medical development center emerging frontier technology joint research project(shdc12018125)。
文摘Objective:This study explored the myocardial protection role of Jujuboside A through an ischemia–hypoxia–reperfusion(IHR)model.Materials and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish an aging and IHR model.There are four groups of experiments:Control,IHR,D-gal+IHR,and D-gal+IHR+Jujuboside A.Cells viability,Adenosine triphosphate(ATP),reactive oxygen species(ROS),nicotinamide adenine dinucleotide(NAD+),nicotinamide adenine dinucleotide hydride(NADH)content,and NAD+/NADH ratio were detected using biochemical methods.Inflammatory cytokines level was detected by enzyme-linked immunosorbent assay.The expression of CD38,Recombinant NLR Family,pyrin domain-containing protein 3(NLRP3),and silent mating type information regulation 2homolog 3(SIRT3)protein was detected by Western blotting.Results:Compared to the IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and SIRT3 protein expression decreased,ROS level and inflammatory cytokines increased,and CD38 and NLRP3 proteins raised in the D-gal+IHR group.Compared to the D-gal+IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and expression of SIRT3 protein increased,ROS level and inflammatory cytokines level decreased,and expression of the CD38 and NLRP3proteins decreased in the D-gal+IHR+Jujuboside A group.Conclusions:Jujuboside A inhibited the expression of CD38,improved energy metabolism disorder,and mitochondrial function,and decreased inflammation in D-gal-induced H9c2 cells.
文摘Objective: To observe the effects of Cistanche desertica polysaccharides (CDP) on the learning and memory functions and cerebral ultrastructure in experimental aging mice. Methods: CDP was administrated intragastrically 50 or 100 mg/kg per day for 64 successive days to experimental aging model mice induced by D￣galactose, then the learning and memory functions of mice were estimated by step￣down test and Y￣maze test; organelles of brain tissue and cerebral ultrastructure were observed by transmission electron microscope and physical strength was determined by swimming test. Results: CDP could obviously enhance the learning and memory functions ( P <0.01) and prolong the swimming time ( P <0.05), decrease the number of lipofuscin and slow down the degeneration of mitochondria in neurons( P <0.05), and improve the degeneration of cerebral ultra￣structure in aging mice. Conclusion: CDP could improve the impaired physiological function and alleviate cerebral morphological change in experimental aging mice.
