The aim of this work was to develop a liquid chromatography-tandem mass spectrometry method for the determination of milk allergen and egg allergen in food products.Signature peptides GGLEPINFQTAADQAR,VGINYWLAHK,VLVLD...The aim of this work was to develop a liquid chromatography-tandem mass spectrometry method for the determination of milk allergen and egg allergen in food products.Signature peptides GGLEPINFQTAADQAR,VGINYWLAHK,VLVLDTDYK,FFVAPFPEVFGK,and NAVPITPTLNR were confirmed and synthesized as the quantitative peptide of ovalbumin,α-lactalbumin,β-lactoglobulin,α_(S1)-casein andα_(S2)-casein,the relative isotope-labeled internal standards were used in the quantitative analysis.Linear range was in the range of0.5-5000.0 nmol/L for egg and milk allergen in bread,cake,cookie,rice crust and wheat flour samples with free from egg and milk,the limits of detection of milk allergens and egg allergen were in the range between0.94 mg/100 g and 56.71 mg/100 g,limits of quantification of milk allergens and egg allergen were in the range between 2.36 mg/100 g and 141.78 mg/100 g.The recoveries ranged from 76.7%to 122.8%,the relative standard deviations were in the range of 1.60%-15.60%.The developed method has been successfully used for the detection of egg and milk allergen in various food samples.展开更多
BACKGROUND： Current studies related to the effects of proanthocyanidins on Alzheimer＇s disease have focused primarily on the signal transduction pathway of cellular apoptosis. However, the influence of p53 gene expr...BACKGROUND： Current studies related to the effects of proanthocyanidins on Alzheimer＇s disease have focused primarily on the signal transduction pathway of cellular apoptosis. However, the influence of p53 gene expression on cell cycle regulation, with regard to the protective mechanisms of proanthocyanidins, has not been reported. OBJECTIVE： To observe the effect of proanthocyanidins on cell cycle distribution, cellular apoptosis and p53 gene expression in β-amyloid peptide （25-35） （Aβ25-35）-induced PC12 cells cultured in serum-free media, and to investigate the molecular neuroprotective mechanisms of proanthocyanidins with regard to cell cycle regulation. DESIGN, TIME AND SETTING： A parallel, controlled, at the Institute of Biochemistry and Molecular Biology cellular, and molecular study was performed Guangdong Medical College from July 2006 to July 2008. MATERIALS： Proanthocyanidins were provided by Nanjing Xuezi Medical and Chemical Research Center, China; Aβ25-35 was provided by Sigma, USA; PC12 cells were provided by the Institute of Basic Medical Science, Academy of Military Medical Sciences; and rabbit anti-p53 polyclonal antibody was provided by Santa Cruz Biotechnology, USA. METHODS： PC12 cells were cultured in serum-free media for 24 hours. Cells from the model group were treated with 25 μmol/L Aβ25-35 for 24 hours. Cells in the drug protection group were pre-treated with 30 mg/L proanthocyanidins for 1 hour and then treated with 25 μmol/LAβ2^-35 for 24 hours. The control group was not treated. MAIN OUTCOME MEASURES： Flow cytometry was used to detect cell cycle distribution and rate of apoptosis; reverse-transcriptase polymerase chain reaction was used to detect p53 mRNA expression; and Western blot was used to detect p53 protein expression. RESULTS： After treating with 25 μmol/LAβ25-35 for 24 hours, the rate of apoptosis and the percentage of cells in S phase were significantly increased （P 〈 0.01 ）, and p53 mRNA and protein expressions were decreased. Pretreatment with proanthocyanidins for 1 hour blocked the increase in apoptosis and the percentage of cells in S phase in Aβ25-35-induced PC12 cells （P 〈 0.01 ） and increased p53 mRNA and protein expressions. CONCLUSION： Proanthocyanidins blocked apoptosis and S-phase arrest in Aβ25-35-induced PC12 cells cultured in serum-free media. The protective mechanism could be related to increased p53 mRNA and protein expressions.展开更多
BACKGROUND：Studies have demonstrated that hydrogen sulfide（H2S） levels are 55% lower in brains of Alzheimer＇s disease（AD） patients than in age-matched normal individuals,which suggests that H2S might be involved...BACKGROUND：Studies have demonstrated that hydrogen sulfide（H2S） levels are 55% lower in brains of Alzheimer＇s disease（AD） patients than in age-matched normal individuals,which suggests that H2S might be involved in some aspects of AD pathogenesis.OBJECTIVE：To observe the protective mechanisms of varied concentrations of H2S against β-amyloid-peptide（Aβ） induced apoptosis in pheochromoytoma（PC12） cells,and to analyze the pathway of action.DESIGN,TIME AND SETTING：A controlled,observational,in vitro experiment was performed at Neurophysiology Laboratory in Zhongshan Medical School,Sun Yat-sen University between July 2006 and May 2007.MATERIALS：PC12 cells were provided by the Animal Experimental Center of Medical School of Sun Yat-sen University.Glybenclamide,rhodamine123,and dihydrorhodamine123 were purchased from Sigma（USA）.METHODS：PC12 cells were incubated at 37 ℃ in a 5% CO2-enriched incubator with RPMI-1640 medium,supplemented with 5% horse-serum and 10% fetal bovine serum.Cells in logarithmic growth curves received different treatment：The PC12 cells were maintains at 37 ℃ with the original medium,then incubated in Aβ25-35,sodium hydrosulfide（NaHS）,glybenclamide,NaHS＋ Aβ25-35,or pretreated with glybenclamide 30 minutes prior to administration of and Aβ25-35,respectively.MAIN OUTCOME MEASURES：（1） The survival rate of PC12 cells was detected by MTT assay and Hoechst staining.（2） The apoptosis rate of PC12 cells was detected utilizing flow cytometry with propidium iodide staining,and morphological changes of apoptotic cells were observed.（3） The mitochondrial membrane potential was detected by Rhodamine123-combined flow cytometry.（4） The intracellular reactive oxygen species content was detected by dihydrorhodamine123-combined flow cytometry.RESULTS：Aβ25-35 induced significantly decreased viability and increased percentage of apoptosis in PC12 cells,as well as dissipated mitochondrial membrane potential expression and an overproduction of reactive oxygen species.When PC12 cells were co-treated with NaHS and Aβ25-35,the decreased cell viability induced by 20 μmol/L Aβ25-35 was concentration-dependently blocked by NaHS（50,100,and 200 μmol/L）.NaHS（100 μmol/L） obviously reduced the percentage of apoptotic PC12 cells induced by 20 μmol/L Aβ25-35.In addition,100 μmol/L NaHS inhibited mitochondrial membrane potential dissipation and reactive oxygen species overproduction.When the ATP-sensitive K channel（KATP） inhibitor,glybenclamide,was administered 30 minutes prior to NaHS and Aβ25-35 treatment,the NaHS-dependent cellular protection was partly blocked.This resulted in reduced PC12 cell viability and increased the percentage of apoptosis,as well as significantly blocked mitochondrial membrane potential preservation and inhibited reactive oxygen species overproduction due to NaHS treatment.CONCLUSION：NaHS protected PC12 cells against Aβ25-35-induced damage.NaHS-dependent cellular protection was associated with mitochondrial membrane potential preservation and inhibition of reactive oxygen species overproduction.The KATP channel inhibitor,glybenclamide,significantly blocked the cellular protective effects of NaHS,indicating that KATP channel activation plays an important role in NaHS-induced protection of PC12 cells to Aβ25-35-induced damage.展开更多
Alzheimer’s disease(AD)is the most common neurodegenerative disease characterized by cognitive decline and memory impairment.Many lines of evidence indicate that excessiveβ-amyloid peptide(Aβ)generation and aggrega...Alzheimer’s disease(AD)is the most common neurodegenerative disease characterized by cognitive decline and memory impairment.Many lines of evidence indicate that excessiveβ-amyloid peptide(Aβ)generation and aggregation play pivotal roles in the initiation of AD,leading to various biochemical alteration including oxidative damage,mitochondrial dysfunction,neuroinflammation,signaling pathway and finally resulting in neuronal death.AD has a complex pathogenic mechanism,and a single-target approach for anti-AD strategy is thus full of challenges.To overcome these limitations,the present study focused to review on one of multiple target-compounds,(-)-epigallocatechin-3-gallate(EGCG)for the prevention and treatment of AD.EGCG is a main bioactive polyphenol in green tea and has been reported to exert potent neuroprotective properties in a wide array of both cellular and animal models in AD.This review demonstrated multiple neuroprotective efficacies of EGCG by focusing on the involvement of Aβ-evoked damage and its Aβregulation.Furthermore,to understand its mechanism of action on the brain,the permeability of the blood-brain barrier was also discussed.展开更多
To explore the effects of Yizhi Capsule （益智胶囊, YZC） on learning and memory disorder and β-amyloid peptide induced neurotoxicity in rats. Methods： Various doses of YZC were administered to Sprague-Dawley （SD）...To explore the effects of Yizhi Capsule （益智胶囊, YZC） on learning and memory disorder and β-amyloid peptide induced neurotoxicity in rats. Methods： Various doses of YZC were administered to Sprague-Dawley （SD） rats for 8 consecutive days, twice a day. On the 8th day of the experiment, scopolamine hydrobromide was intraperitoneally injected to every rat and Morris water maze test and shuttle dark avoidance test were carried out respectively to explore the changes of learning and memory capacities in the rats. Resides, after the cerebral cortical neurons of newborn SD rats aged within 3 days were cultured in vitro for 7 days, drug serum containing YZC was added to the cultured neurons before or after β amyloid peptide25-35 （Aβ25-35） intoxication to observe the protective effect of YZC on neurotoxicity by MTT assay and to determine the LDH content in the supernatant. Results： Compared with those untreated with YZC, the rats having received YZC treatment got superiority in shorter time of platform seeking in Morris water maze test, as well as elongated latent period and less times of error in shuttle dark avoidance test. On the cultured neurons, YZC drug serum could effectively increase the survival rate of Aβ25-35 intoxicated neurons and reduce the LDH contents in cultured supernatant. Conclusion： YZC has an action of improving learning and memory disorder, and good protective effect on Aβ25-35 induced neurotoxicity in SD rats. KEY WORDS展开更多
Objective To study the therapeutic effects of Ginsenoside Rg-1 and Gastrodine on rats model of Alzheimer's disease(AD). Methods Aggregated β-Amyloid peptide (25-35) was injected into the lateral ventricle of rats...Objective To study the therapeutic effects of Ginsenoside Rg-1 and Gastrodine on rats model of Alzheimer's disease(AD). Methods Aggregated β-Amyloid peptide (25-35) was injected into the lateral ventricle of rats to establish AD models. Ginsenoside Rg-1, Gastrodine and Ginsenoside Rg-1+Gastrodine were intraperitoneally injected into rats of each test group(Ginsenoside Rg-1∶10mg/kg·day; Gastrodine 100mg/kg·day) for 4 weeks, the rats of control group received equal volume of saline. Passive avoidance task and Morris maze test were done to assess the ability of learning and memory. The content of superoxide dismutase (SOD), malondiadehyde (MDA), total-antioxidative capability (T-AOC), Choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissue were measured. Results Ginsenoside Rg-1 and Gastrodine significantly improved learning and memory deficits in the rats with AD induced by β-Amyloid peptide (25-35) (P<0.05). Ginsenoside Rg-1+Gastrodine group were better than Ginsenoside Rg-1 group and Gastrodine group (P<0.05). Ginsenoside Rg-1 reduced the increase of SOD, MDA, but inhibited the decrease of T-AOC, AchE and ChAT; Gastrodine reduced the increase of SOD, MDA, while inhibited the decrease of T-AOC. Gastrodine could also prevent the activity of ChAT and AchE decline in AD rats. Conclusion Both Ginsenoside Rg-1 and Gastrodine have therapeutic effects on rats with AD; Ginsenoside Rg-1 and Gastrodine injection at the same time were better than only using one of them. Their mechanisms might different. Ginsenoside Rg-1 can not only inhibit peroxidation but also increase the activity of AchE and ChAT in brain tissue, while Gastrodine can inhibit peroxidation only, but it can't prevent the decline of ChAT and AchE activity in AD rats.展开更多
Deposition of amyloid in the brain is a critical step in the pathogenesis of Alzheimer＇s disease. The endocytosis of β-amyloid peptide （Aβ） is an important factor among the many factors that contribute to the gen...Deposition of amyloid in the brain is a critical step in the pathogenesis of Alzheimer＇s disease. The endocytosis of β-amyloid peptide （Aβ） is an important factor among the many factors that contribute to the genesis of amyloid deposits. Since cholesterol participates in many important physiological processes, the present work investigated the relationship between the cellular cholesterol content and the endocytosis of the exogenic Aβ, and found that reduction of the cholesterol content by methyl-β-cyclodextrin could reduce the endocytosis of AI3. The study indicates that the endocytosis of Aβ is partly mediated by cholesterol.展开更多
Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis sh...Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis showed that brain-derived neurotrophic factor provided neuroprotection against cellular apoptosis by suppressing the decline in β-amyloid（25 35）-induced cell activity and the increasing ratio of Bax/Bcl-2. After treating pheochromocytoma cells with tyrosine kinase receptor B receptor inhibitor K252a, brain-derived neurotrophic factor reverses the above- mentioned changes. The experimental findings suggested that brain-derived neurotrophic factor prevented β-amyloid peptide-induced cellular apoptosis by modulating Bax/Bcl-2 expression, and this effect was associated with binding to the specific tyrosine kinase receptor B receptor.展开更多
Ratanasampil (RNSP) is a traditional Tibetan medicine used for the treatment of stroke and cerebrovascular diseases. Previous discoveries that RNSP can reduce β-amyloid protein levels and increase learning and memory...Ratanasampil (RNSP) is a traditional Tibetan medicine used for the treatment of stroke and cerebrovascular diseases. Previous discoveries that RNSP can reduce β-amyloid protein levels and increase learning and memory in Alzheimer’s mouse models (Tg2576) led us to investigate whether RNSP can improve cognitive functions in Alzheimer’s patients. In this study, 146 AD patients living in Qinghai province received either one gram or 0.33 gram daily of RNSP for 16 weeks. Placebo patients received Piracetam. Serum Aβ40 and Aβ42 levels were measured at the beginning of the study and after 4 and 16 weeks of treatment. Compared to the same group before treatment, MMSE scores, ADAS-cog scores and ADL scores were significantly improved (p 0.05, p > 0.05). After 16-week treatment, serum TNF-α, IL-1β, IL-6 and Aβ42 levels were significantly decreased (p < 0. 01) in the high-dose RNSP group, whereas no significant differences were found in the low-dose and placebo groups. The Aβ42/Aβ40 ratio was significantly decreased after 4-week and 16-week treatment in the high-dose RNSP group (p < 0. 05, p < 0.01). Furthermore, serum Aβ42 concentrations had a strong positive correlation with TNF-α, IL-1β and IL-6 levels. There were no observable adverse effects in either treatment or control groups. We conclude that further clinical trials of RNSP in Alzheimer disease are warranted.展开更多
基金supported by National Key Research and Development Program of China(2019YFC1606400)Science and Technology Project of State Administration for Market Regulation(2021MK023)+1 种基金Hebei Province High-level Talent Funding Program(A201901008)Research Project of Hebei Administration for Market Regulation(2020ZD12)。
文摘The aim of this work was to develop a liquid chromatography-tandem mass spectrometry method for the determination of milk allergen and egg allergen in food products.Signature peptides GGLEPINFQTAADQAR,VGINYWLAHK,VLVLDTDYK,FFVAPFPEVFGK,and NAVPITPTLNR were confirmed and synthesized as the quantitative peptide of ovalbumin,α-lactalbumin,β-lactoglobulin,α_(S1)-casein andα_(S2)-casein,the relative isotope-labeled internal standards were used in the quantitative analysis.Linear range was in the range of0.5-5000.0 nmol/L for egg and milk allergen in bread,cake,cookie,rice crust and wheat flour samples with free from egg and milk,the limits of detection of milk allergens and egg allergen were in the range between0.94 mg/100 g and 56.71 mg/100 g,limits of quantification of milk allergens and egg allergen were in the range between 2.36 mg/100 g and 141.78 mg/100 g.The recoveries ranged from 76.7%to 122.8%,the relative standard deviations were in the range of 1.60%-15.60%.The developed method has been successfully used for the detection of egg and milk allergen in various food samples.
基金Key Discipline Key Projects in Guangdong Province (9808)
文摘BACKGROUND： Current studies related to the effects of proanthocyanidins on Alzheimer＇s disease have focused primarily on the signal transduction pathway of cellular apoptosis. However, the influence of p53 gene expression on cell cycle regulation, with regard to the protective mechanisms of proanthocyanidins, has not been reported. OBJECTIVE： To observe the effect of proanthocyanidins on cell cycle distribution, cellular apoptosis and p53 gene expression in β-amyloid peptide （25-35） （Aβ25-35）-induced PC12 cells cultured in serum-free media, and to investigate the molecular neuroprotective mechanisms of proanthocyanidins with regard to cell cycle regulation. DESIGN, TIME AND SETTING： A parallel, controlled, at the Institute of Biochemistry and Molecular Biology cellular, and molecular study was performed Guangdong Medical College from July 2006 to July 2008. MATERIALS： Proanthocyanidins were provided by Nanjing Xuezi Medical and Chemical Research Center, China; Aβ25-35 was provided by Sigma, USA; PC12 cells were provided by the Institute of Basic Medical Science, Academy of Military Medical Sciences; and rabbit anti-p53 polyclonal antibody was provided by Santa Cruz Biotechnology, USA. METHODS： PC12 cells were cultured in serum-free media for 24 hours. Cells from the model group were treated with 25 μmol/L Aβ25-35 for 24 hours. Cells in the drug protection group were pre-treated with 30 mg/L proanthocyanidins for 1 hour and then treated with 25 μmol/LAβ2^-35 for 24 hours. The control group was not treated. MAIN OUTCOME MEASURES： Flow cytometry was used to detect cell cycle distribution and rate of apoptosis; reverse-transcriptase polymerase chain reaction was used to detect p53 mRNA expression; and Western blot was used to detect p53 protein expression. RESULTS： After treating with 25 μmol/LAβ25-35 for 24 hours, the rate of apoptosis and the percentage of cells in S phase were significantly increased （P 〈 0.01 ）, and p53 mRNA and protein expressions were decreased. Pretreatment with proanthocyanidins for 1 hour blocked the increase in apoptosis and the percentage of cells in S phase in Aβ25-35-induced PC12 cells （P 〈 0.01 ） and increased p53 mRNA and protein expressions. CONCLUSION： Proanthocyanidins blocked apoptosis and S-phase arrest in Aβ25-35-induced PC12 cells cultured in serum-free media. The protective mechanism could be related to increased p53 mRNA and protein expressions.
基金Medical Research Foundation of Shaoguan, Guangdong Province, No.Y08042
文摘BACKGROUND：Studies have demonstrated that hydrogen sulfide（H2S） levels are 55% lower in brains of Alzheimer＇s disease（AD） patients than in age-matched normal individuals,which suggests that H2S might be involved in some aspects of AD pathogenesis.OBJECTIVE：To observe the protective mechanisms of varied concentrations of H2S against β-amyloid-peptide（Aβ） induced apoptosis in pheochromoytoma（PC12） cells,and to analyze the pathway of action.DESIGN,TIME AND SETTING：A controlled,observational,in vitro experiment was performed at Neurophysiology Laboratory in Zhongshan Medical School,Sun Yat-sen University between July 2006 and May 2007.MATERIALS：PC12 cells were provided by the Animal Experimental Center of Medical School of Sun Yat-sen University.Glybenclamide,rhodamine123,and dihydrorhodamine123 were purchased from Sigma（USA）.METHODS：PC12 cells were incubated at 37 ℃ in a 5% CO2-enriched incubator with RPMI-1640 medium,supplemented with 5% horse-serum and 10% fetal bovine serum.Cells in logarithmic growth curves received different treatment：The PC12 cells were maintains at 37 ℃ with the original medium,then incubated in Aβ25-35,sodium hydrosulfide（NaHS）,glybenclamide,NaHS＋ Aβ25-35,or pretreated with glybenclamide 30 minutes prior to administration of and Aβ25-35,respectively.MAIN OUTCOME MEASURES：（1） The survival rate of PC12 cells was detected by MTT assay and Hoechst staining.（2） The apoptosis rate of PC12 cells was detected utilizing flow cytometry with propidium iodide staining,and morphological changes of apoptotic cells were observed.（3） The mitochondrial membrane potential was detected by Rhodamine123-combined flow cytometry.（4） The intracellular reactive oxygen species content was detected by dihydrorhodamine123-combined flow cytometry.RESULTS：Aβ25-35 induced significantly decreased viability and increased percentage of apoptosis in PC12 cells,as well as dissipated mitochondrial membrane potential expression and an overproduction of reactive oxygen species.When PC12 cells were co-treated with NaHS and Aβ25-35,the decreased cell viability induced by 20 μmol/L Aβ25-35 was concentration-dependently blocked by NaHS（50,100,and 200 μmol/L）.NaHS（100 μmol/L） obviously reduced the percentage of apoptotic PC12 cells induced by 20 μmol/L Aβ25-35.In addition,100 μmol/L NaHS inhibited mitochondrial membrane potential dissipation and reactive oxygen species overproduction.When the ATP-sensitive K channel（KATP） inhibitor,glybenclamide,was administered 30 minutes prior to NaHS and Aβ25-35 treatment,the NaHS-dependent cellular protection was partly blocked.This resulted in reduced PC12 cell viability and increased the percentage of apoptosis,as well as significantly blocked mitochondrial membrane potential preservation and inhibited reactive oxygen species overproduction due to NaHS treatment.CONCLUSION：NaHS protected PC12 cells against Aβ25-35-induced damage.NaHS-dependent cellular protection was associated with mitochondrial membrane potential preservation and inhibition of reactive oxygen species overproduction.The KATP channel inhibitor,glybenclamide,significantly blocked the cellular protective effects of NaHS,indicating that KATP channel activation plays an important role in NaHS-induced protection of PC12 cells to Aβ25-35-induced damage.
文摘Alzheimer’s disease(AD)is the most common neurodegenerative disease characterized by cognitive decline and memory impairment.Many lines of evidence indicate that excessiveβ-amyloid peptide(Aβ)generation and aggregation play pivotal roles in the initiation of AD,leading to various biochemical alteration including oxidative damage,mitochondrial dysfunction,neuroinflammation,signaling pathway and finally resulting in neuronal death.AD has a complex pathogenic mechanism,and a single-target approach for anti-AD strategy is thus full of challenges.To overcome these limitations,the present study focused to review on one of multiple target-compounds,(-)-epigallocatechin-3-gallate(EGCG)for the prevention and treatment of AD.EGCG is a main bioactive polyphenol in green tea and has been reported to exert potent neuroprotective properties in a wide array of both cellular and animal models in AD.This review demonstrated multiple neuroprotective efficacies of EGCG by focusing on the involvement of Aβ-evoked damage and its Aβregulation.Furthermore,to understand its mechanism of action on the brain,the permeability of the blood-brain barrier was also discussed.
文摘To explore the effects of Yizhi Capsule （益智胶囊, YZC） on learning and memory disorder and β-amyloid peptide induced neurotoxicity in rats. Methods： Various doses of YZC were administered to Sprague-Dawley （SD） rats for 8 consecutive days, twice a day. On the 8th day of the experiment, scopolamine hydrobromide was intraperitoneally injected to every rat and Morris water maze test and shuttle dark avoidance test were carried out respectively to explore the changes of learning and memory capacities in the rats. Resides, after the cerebral cortical neurons of newborn SD rats aged within 3 days were cultured in vitro for 7 days, drug serum containing YZC was added to the cultured neurons before or after β amyloid peptide25-35 （Aβ25-35） intoxication to observe the protective effect of YZC on neurotoxicity by MTT assay and to determine the LDH content in the supernatant. Results： Compared with those untreated with YZC, the rats having received YZC treatment got superiority in shorter time of platform seeking in Morris water maze test, as well as elongated latent period and less times of error in shuttle dark avoidance test. On the cultured neurons, YZC drug serum could effectively increase the survival rate of Aβ25-35 intoxicated neurons and reduce the LDH contents in cultured supernatant. Conclusion： YZC has an action of improving learning and memory disorder, and good protective effect on Aβ25-35 induced neurotoxicity in SD rats. KEY WORDS
文摘Objective To study the therapeutic effects of Ginsenoside Rg-1 and Gastrodine on rats model of Alzheimer's disease(AD). Methods Aggregated β-Amyloid peptide (25-35) was injected into the lateral ventricle of rats to establish AD models. Ginsenoside Rg-1, Gastrodine and Ginsenoside Rg-1+Gastrodine were intraperitoneally injected into rats of each test group(Ginsenoside Rg-1∶10mg/kg·day; Gastrodine 100mg/kg·day) for 4 weeks, the rats of control group received equal volume of saline. Passive avoidance task and Morris maze test were done to assess the ability of learning and memory. The content of superoxide dismutase (SOD), malondiadehyde (MDA), total-antioxidative capability (T-AOC), Choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissue were measured. Results Ginsenoside Rg-1 and Gastrodine significantly improved learning and memory deficits in the rats with AD induced by β-Amyloid peptide (25-35) (P<0.05). Ginsenoside Rg-1+Gastrodine group were better than Ginsenoside Rg-1 group and Gastrodine group (P<0.05). Ginsenoside Rg-1 reduced the increase of SOD, MDA, but inhibited the decrease of T-AOC, AchE and ChAT; Gastrodine reduced the increase of SOD, MDA, while inhibited the decrease of T-AOC. Gastrodine could also prevent the activity of ChAT and AchE decline in AD rats. Conclusion Both Ginsenoside Rg-1 and Gastrodine have therapeutic effects on rats with AD; Ginsenoside Rg-1 and Gastrodine injection at the same time were better than only using one of them. Their mechanisms might different. Ginsenoside Rg-1 can not only inhibit peroxidation but also increase the activity of AchE and ChAT in brain tissue, while Gastrodine can inhibit peroxidation only, but it can't prevent the decline of ChAT and AchE activity in AD rats.
基金Supported by the National Key Basic Research and Development (973) Program of China (No. 2004CB20005)
文摘Deposition of amyloid in the brain is a critical step in the pathogenesis of Alzheimer＇s disease. The endocytosis of β-amyloid peptide （Aβ） is an important factor among the many factors that contribute to the genesis of amyloid deposits. Since cholesterol participates in many important physiological processes, the present work investigated the relationship between the cellular cholesterol content and the endocytosis of the exogenic Aβ, and found that reduction of the cholesterol content by methyl-β-cyclodextrin could reduce the endocytosis of AI3. The study indicates that the endocytosis of Aβ is partly mediated by cholesterol.
文摘Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis showed that brain-derived neurotrophic factor provided neuroprotection against cellular apoptosis by suppressing the decline in β-amyloid（25 35）-induced cell activity and the increasing ratio of Bax/Bcl-2. After treating pheochromocytoma cells with tyrosine kinase receptor B receptor inhibitor K252a, brain-derived neurotrophic factor reverses the above- mentioned changes. The experimental findings suggested that brain-derived neurotrophic factor prevented β-amyloid peptide-induced cellular apoptosis by modulating Bax/Bcl-2 expression, and this effect was associated with binding to the specific tyrosine kinase receptor B receptor.
文摘Ratanasampil (RNSP) is a traditional Tibetan medicine used for the treatment of stroke and cerebrovascular diseases. Previous discoveries that RNSP can reduce β-amyloid protein levels and increase learning and memory in Alzheimer’s mouse models (Tg2576) led us to investigate whether RNSP can improve cognitive functions in Alzheimer’s patients. In this study, 146 AD patients living in Qinghai province received either one gram or 0.33 gram daily of RNSP for 16 weeks. Placebo patients received Piracetam. Serum Aβ40 and Aβ42 levels were measured at the beginning of the study and after 4 and 16 weeks of treatment. Compared to the same group before treatment, MMSE scores, ADAS-cog scores and ADL scores were significantly improved (p 0.05, p > 0.05). After 16-week treatment, serum TNF-α, IL-1β, IL-6 and Aβ42 levels were significantly decreased (p < 0. 01) in the high-dose RNSP group, whereas no significant differences were found in the low-dose and placebo groups. The Aβ42/Aβ40 ratio was significantly decreased after 4-week and 16-week treatment in the high-dose RNSP group (p < 0. 05, p < 0.01). Furthermore, serum Aβ42 concentrations had a strong positive correlation with TNF-α, IL-1β and IL-6 levels. There were no observable adverse effects in either treatment or control groups. We conclude that further clinical trials of RNSP in Alzheimer disease are warranted.
