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Objective: Through metabonomics research methods,the effect of Siwutang on metabolites and metabolic pathways in natural aging mice were observed.The related targets and mechanism of Siwutang intervention in natural aging mice were analyzed. Method: Taking 20-month-old natural aging model mice(equivalent to 60-65 years old of human beings) as the experimental subjects,at the same time,mice aged 3 months were established as the youth group.UPLC-Q-TOF-MS technique was employed to analyze the mouse plasma with mobile phase of acetonitrile(containing 0.1%formic acid)-0.1%formic acid solution for gradient elution and positive ion mode of electrospray ionization,and the metabolic markers were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA),and their metabolic pathways were summarized. Result: Siwutang had obvious reversal effect on the expression levels of 16 aging-related metabolites,among which 9 metabolic markers were statistically significant(PConclusion: Siwutang can affect the metabolites in the plasma of 20-month-old natural aging mice,and the metabolic disorder during the aging process of mice can be improved by glutathione metabolism,pyrimidine metabolism,selenium amino acid metabolism and other pathways,and this paper can provide biological information for the study of material basis of this compound for aging.
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Objective: To investigate effect of Schisandrae Chinensis Fructus powder in D-galactose-induced aging model mice. Methods: Seventy-two Kunming mice were randomly divided into normal group, model group, Naokangling group (0.810 g/kg), and low-, mid-, and high-dose (3.00, 1.50, 0.75 g/kg) Schisandrae Chinensis Fructus powder groups. Aging mice model was established by sc injection of D-galactose 1.25 g/kg at neck back once daily for 40 d. Naokangling and Schisandrae Chinensis Fructus powder were orally administrated on day 11 for 30 d. Then the learning and memory ability was assessed by step-through test on day 39. Two hours after the last administration, the contents of malonaldehyde (MDA) in brain homogenate, liver homogenate, and plasma and the activity of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) in whole blood were detected; The morphological changes of brain, liver, thymus, and spleen in each group of mice were observed by light microscope. Results: Compared with model groups, the Schisandrae Chinensis Fructus powder groups can improve the incubation period and reduce the number of times of light and dark shuttle of model mice; The Schisandrae Chinensis Fructus powder groups can reduce the level of MDA in plasma, brain, and liver homogenate, and increase the levels of CAT, SOD, and GSH in the whole blood in different degrees; It also can elevate the index of spleen, thymus, and brain, and decrease the indexes of liver in different degrees. Conclusion: Schisandrae Chinensis Fructus powder can significantly improve the biochemical indexes and pathological status of aging model mice.
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Objective To investigate the protective mechanism of ginsenoside Rg1 on hippocampus of aging mice induced by D-galactose. Methods Forty nestin-green fluorescent protein (GFP) transgenic mice, aged 6-8 weeks, were randomly divided into four groups: control group, ginsenoside Rg1 control group, ginsenoside Rg1 therapy group, and model group. Learning and memory abilities were measured by Morris water maze after the modeling completed. Frozen sections were made to survey the hippocampus fluorescence intensity. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to detect the aging level of hippocampus. The activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and contents of malonaldehyde (MDA) in hippocampus were tested by chromatometry. Enzyme-linked immunosorbent assay (ELISA) was used to test the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α proinflammatory cytokins in hippocampus. The levels of p53 and p21 were detected by Western blotting. Results The learning and memory capacities of the aging model group were decreased compared with those of the drug therapy group; The fluorescence intensity in the dentat gyrus (DG) of hippocampus of the drug therapy group was increased compared with that of the model group; The SA-β-Gal positive granules in section of brain tissue of the aging model group were increased compared with those of the drug group and drug therapy group; The activitives of SOD and T-AOC of the drug therapy group were increased compared with those of the aging model group while the content of MDA was decreased. The levels of IL-1β, IL-6, and TNF-α were decreased in the drug therapy group compared with those in the aging model group. The levels of p53 and p21 were decreased in the drug therapy group compared with those in the aging model group. Conclusion Ginsenoside Rg1 can antagonistic D-galactose and delay the aging of hippocampus. In addition, improvement of anti-oxidant ability and regulation of the level of p53-p21 pathway may be the underlying anti-aging mechanism of ginsenoside Rg1.
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D-galactose (D-gal)-induced aging model is widely used in the study of the pharmacodynamics of antiaging drugs. The model has a shorter life-span, disorders in learning and memory, reduced immune function and other aging characteristics. Regular and quantitative injection of D-gal solution to rats can produce symptoms of natural aging models that are used in screening of antiaging drugs, and their pharmacological activities. This paper provides a summary of the mechanism of rat model induced with D-gal solution. The methods of building and evaluation of the aging models are provided. The theoretical basis is included to facilitate the subsequent research and experiment in the mechanism study of aging and antiaging medicines.
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Objective To explore the effect of D-galactose(D-gal) on murine pancreatic injury and its pathogenesis.Methods C57BL/6J mice were randomly divided into control group and D-gal model group [D-gal 120 mg/(kg · d) for 42 days].On the 2nd day after drug injection completed,the peripheral blood was taken for measuring the level of fasting blood glucose(FBG) and fasting insulin(FINS);and then the organ index of pancreas was calculated by the ratio of pancreatic wet weight(mg) and mouse body weight(g);HE stain was routinely prepared to observe the histologic structure of pancreatic tissue;the TEM was used to analyze ultrastructural changes of pancreatic cells;the pancreatic frozen sections were prepared to test senescence-associated β-galactosidase (SA-β-gal) and its relative absorbance(RA) of positively stained cells in the pancreatic islets;immunohistochemistry assays to study advanced glycation end products (AGEs) and its RA;pancreas tissue homogenate was made to detect the content of superoxide dismutase(SOD),malonaldehyde(MDA) and total antioxidant capacity(T-AOC).Results In D-gal group mice,the FBG increased(P＜0.05) and FINS reduced;pancreas wet weight and organ increased obviously (P＜0.01);light microscopic structure of the pancreas presented without typical pathologic change,however the single nucleated cell's area within the islet was increased significantly(P＜0.05);the pancreas endocrine and exocrine cells were showed the ultrastructure damaged and lipofuscin formation increased;the RA of positive pancreas cells in SA-β-gal staining increased(P＜0.05);the RA of AGEs positive regional expression markedly increased (P＜0.01);the content of SOD and T-AOC decreased (P ＜ 0.05),the content of MDA increased (P ＜ 0.01).Conclusions Aging mice model replicated by D-gal can cause the pancreatic injury,its mechanisms may be closely related to oxidative injury of pancreatic cells caused by D-gal.
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Objective This study aimed to investigate the role of pyrroloquinoline quinone (PQQ) in repairing oxidative nerve cells,and to study the antioxidant capacity of PQQ on the oxidative damage of rats caused by apolexis,as well as the effects on learning and memory abilities of apolexis rats.Methods Oxidative damage of PC12 was induced by H2O2,and the repairing rate of PQQ on oxidative PC12 cells was tested by methylthiazolyldiphenyl-tetrazolium bromide assay kit.The 18-month-old male SD rats were administered PQQ (0,10,20,40 mg/kg).After 4 weeks,Morris water maze test was used to test the learning and memory ability.After 6 weeks,serum and brain tissue related indicators and antioxidant capacity were recorded.Results The survival rate of PC12 cells increased from 59.1％ to 90.5％ with 200 nmol/L PQQ.Compared with the apolexis model group,the latency of the PQQ group (20,40 mg/kg) was shortened in the Morris water maze experiment,the swimming distance was reduced,pass-through counts were increased,and the first secure platform pass-through was reduced.Meanwhile,the levels of malondialdehyde and lipofuscin in serum and brain tissue of PQQ group decreased,the levels of superoxide dismutase,glutathione peroxidase vitality,antioxidant capacity of PQQ group (20,40 mg/kg) were enhanced.Conclusion PQQ could repair the oxidative damage of nerve cells,and it was confirmed that PQQ could play the same antioxidant effect in body and brain,and increase the learning and memory ability of apolexis rats.
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Objective:To explore the effects of caffeine on the prevention of Alzheimer's disease (AD).Methods:Use Ethanol as a solvent to extract the caffeine in tea and then injecting 5％ D-galactose saline solution 1ml/d/kg to establish aging model mice.Divide mice randomly into experimental group (high-dose/low-dosecaffeine),positive control group,negative control group,and normal con-trol group (NS) and injecting appropriate drugs for consecutive four weeks.Test superoxyde dismutase (SOD) and malondialdehvde (MDA) periodically.Take mice's hippocampus and use Western blotting to detect the expression of brain derived neurotrophic factor (BDNF) and extracellular signal-regulated kinasesl/2 (p-ERK1/2).Results:The expression of BDNF and p-ERK1/2,negative control group is less than low-dose experimental group and positive control group (P＜0.01);The p-ERK1/2 expression of injecting D-galactose mice was significantly lower than normal group,negative control group compared weth the normal group,the differencd was significant (P＜0.05).The level of SOD in model group was significantly lower than that in normal control group,high,low dose caffeine group and positive control group (P＜0.01),but the level of MDA is opposite.Conclusions:Caffeine can delay aging process by increasing the level of SOD in aging mice,and enhancing the expression of BDNF and P-ERK1/2.Caffeine does a lot to prevent AD.
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Objective To explore the effect of Cortex Eucommiae (CE) extract on oxidative stress markers of brain aging mice. Methods Brain aging mice model was made via subcutaneously administered D-galactose. The ethanol extract of CE was intra-gastrically administered to the model mice. Apoptosis ratio of brain cells of mice was determined by a flow cytometry to evaluate the anti-aging function of CE extract. A series of biomarkers related to oxidation, including malonyldialdehyde (MDA), superoxide dis-mutase (SOD), protein carbonyl (PCO), and nitric oxide (NO) in serum of mice were determined by ELISA. Results Compared with the model mice, the apoptosis ratio of brain cells in the CE extract group decreased significantly (P<0.01). ELISA test results showed that,compared with the normal group, NO and SOD levels in serum of CE extract group were significantly higher (P<0.01). Compared with the model group, MDA and PCO levels in serum of CE extract group were significantly lower (P<0.01), and SOD level was obviously higher (P<0.01). Conclusion The CE extract might play the role of brain anti-aging by the effective attenuation of oxidative damage.
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Objective To explore the effect of Cortex Eucommiae(CE)extract on oxidative stress markers of brain aging mice. Methods Brain aging mice model was made via subcutaneously administered D-galactose. The ethanol extract of CE was intra?gastrically administered to the model mice. Apoptosis ratio of brain cells of mice was determined by a flow cytometry to evaluate the an?ti-aging function of CE extract. A series of biomarkers related to oxidation,including malonyldialdehyde(MDA),superoxide dis?mutase(SOD),protein carbonyl(PCO),and nitric oxide(NO)in serum of mice were determined by ELISA. Results Compared with the model mice,the apoptosis ratio of brain cells in the CE extract group decreased significantly(P<0.01). ELISA test results showed that,compared with the normal group,NO and SOD levels in serum of CE extract group were significantly higher(P<0.01). Compared with the model group,MDA and PCO levels in serum of CE extract group were significantly lower(P<0.01),and SOD level was obviously higher(P<0.01). Conclusion The CE extract might play the role of brain anti-aging by the effective attenuation of ox?idative damage.
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Objective_To investigate the effect of ginsenoside Rg1 on the spleen structure and function of aging rats and its relative mechanism.Methods_Forty SD rats were randomly divided into normal control group, aging model group (D-galactose 120 mg/kg,qd ×42 d), Rg1 intervention group(D-galactose 120 mg/kg,qd ×42 d and Rg1 20 mg/kg, from day 15th,qd ×28 d) and Rg1 control group.After finishing injections the spleen index was meas-ured, paraffin sections were then made to observe spleen microscopic structure.Senescence-associatedβ-Galactosi-dase( SA-β-Gal) stain was used to detect aging splenocytes.The proliferative capacity of splenocytes stimulated with Concanavalin A (ConA) was measured by CCK-8.The content of IL-2,IL-6 and advanced glycosylation end products(AGEs) was detected by ELISA.The level of ROS was analyzed by flow cytometry(FCM).Malondialde-hyde(MDA), superoxide dismutase (SOD) were detected by enzymatic assay.The expression of senescence-associ-ated protein P53,P21 and RB were detected by Western blot analysis.Results_Comparing the Rg1 intervention group with the aging model group, spleen index, splenic white pulp area proportion, the proliferative capacity of splenocytes were significantly increased (P<0.05);The secretory capability of IL-2 and IL-6, the active content of SOD were obviously increased(P<0.01);The percentage of SA-β-Gal positive splenocytes, the productions of ROS and MDA were significantly decreased (P<0.01);The production of AGEs was decreased (P<0.05);The expressions of P53,P21 and Rb were also significantly down-regulated ( P<0.01) .Conclusions_Ginsenoside Rg1 relieves injure of the spleen in aging rats induced by D-galactose.It is suggested that the mechanism may be Rg1 in-hibiting oxidative stress and down-regulating P53-P21-RB signaling pathway.
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Objective: To study the anti-aging effect of polypeptides from Fructus Lycii(PFL) on D-galactose(D-gal) induced aging model mice and the possible mechanism. Methods: Sixty ICR mice were randomly divided nto normal control group, D-gal induced model group, PFL 200, 400 and 800 mg/(kg · d) groups and vitamin E(VitE) 100 mg/(kg · d) group. D-gal aging mouse model was established by cervicodorsal region subcutaneous injection with D-gal(10 mg/kg) once a day for five successive weeks. In the meantime, drugs were given by intragastric administration respectively n PFL and Vit E treatment groups. The effect of PFL on learning and memory ability of mice was observed. After 5 weeks, the superoxide dismutase(SOD) activity, malondialdehyde(MDA) content and telomerase activity in serum, heart, liver and brain tissues of mice were measured. Results: Compared with normal control group, for aging model mice, the weight increasement declined, the number of errors in step-down test increased, the SOD and tolemerase activities in serum heart, liver and brain tissues dropped, and the MDA content was raised, P<0.01. Compared with model group, for the mice in PFL and VitE treatment groups, the weight increasement rised(P<0.01), the error number in step-down test decreased(P<0.05), the SOD activity in serum, heart, liver and brain tissues enhanced, and the MDA content reduced (P<0.01). The telomerase activity in serum and heart of 400, 800 mg/(kg · d) PFL and VitE treatment groups also increased significantly than model group, while that in liver and brain did not change. Conclusion: PFL have anti-aging effect on D-gal induced aging mice, and the action mechanism is related to the increasement of SOD activity, the decreasement of MDA content in serum, heart, liver and brain of D-gal aging mice, and the increasement of telomerase activity in serum and heart.
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Objective To investigate the possibility of taking bees as laboratory animals and establishing the new rapid ag-ing animal model. Methods The bee model was established under environment of high temperature, lack of oxygen, and vibration. The appropriate conditions for establishing the model were investigated by observing the changes of appearance and measuring the activities of the total SOD and GSH-PX in the whole homogenate of bees. Meanwhile, the changes of biopsy were observed. Results Bees aging model could been set up at the conditions of appropriate temperature, hypoxia and noise. The model has obvious indications of aging, such as reduced activity of SOD and GSH-PX, and obviously pathological changes of brain organization and intestinal tissue. The aging indications are not the most seriously and are suit-able for the studies on drug improving the aging indications. Conclusion Being in the enviroment of high temperature (35 ℃), hypoxia and noise for4 hours, can result in the better bee aging model.
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OBJECTIVE:To study the effect of flavonoids of Astragalus complanatus(FAC) on D-galactose-induced sub-acute aging in mice. METHODS:The subacute aging mice model were established with the use of D-galactose,and the effect of FAC on the associated indexes in model mice such as enzymes,immune organ indexes,hypoxia tolerance time,swimming time under hypoxic condition etc were recorded. RESULTS:FAC treatment significantly up-regulated the activity of SOD,down-regulated MDA content,markedly increased the spleen index and thymus index,prolonged the surviving and swimming time markedly under anoxia condition. CONCLUSION:FAC has anti-aging effect and it can enhance mice's abil-ity against hypoxia and fatigue,which is probably associated to the enhancement of the nonspecific immunity in mice.
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With the dose of D-galactose 80mg/kg by sc administration to the female NIH mice for 6 weeks,the sub-acute aging model was established. In order to observe the effect of the polysaccharide (PSP) on anti-aging, the mice were received PSP 200mg/kg