BACKGROUND: Modern pharmacological studies have demonstrated that Panax notoginseng saponins (PNS) can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and be...BACKGROUND: Modern pharmacological studies have demonstrated that Panax notoginseng saponins (PNS) can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer's disease (AD) remains unclear. OBJECTIVE: Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A. DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University. MATERIALS: Ninety healthy Wistar rats of both genders, 15-month-old (n =75) and 3-month-old rats as young controls (n =15), were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd (permission No. Z53021485, Yuxi, Yunan Province, China). Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science. METHODS: This study was performed at the Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each: model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose (5 mL/kg) every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μL ibotenic acid (5 g/L) bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were gavaged with 200 and 100 mg/kg PNS suspension, respectively. Huperzine A suspension (0.3 mg/kg) was used in the huperzine A group. Rats in the other 3 groups were gavaged with a corresponding volume of normal saline. In each group, administration was carried out once per day for 4 consecutive weeks. MAIN OUTCOME MEASURES: After administration, learning and memory abilities were measured by place navigation and spatial probe tests. Recording indices consisted of escape latency (time-to-platform), number of times to find the platform within 2 minutes, number of times the animal crosses the original platform location, and the percent of swimming time in each quadrant. RESULTS: Several rats died due to inflammatory reactions following brain lesion or intragastric administration; therefore, 61 rats were included in the final analysis. Results of spatial navigation test: Escape latency of rats in the model group was significantly prolonged, and number of times to find the platform within 2 minutes were significantly reduced compared with other groups (both P < 0.05). No significant differences in these two indices were measured among the administration groups (all P > 0.05). Results of spatial probe test: Times for crossing the original platform location and percent of time spent in the quadrant of original platform location were significantly less in the model group than in the other groups (P < 0.05). There were no significant differences in these two indices among the administration groups (P > 0.05). CONCLUSION: PNS can remarkably improve spatial learning and memory abilities of rats with AD. The therapeutic effect of PNS is not dose-dependent and is equivalent to the effect of huperzine A.展开更多
Objective Alzheimer's disease(AD)is the most common cause of dementia.The pathophysiology of the disease mostly remains unearthed,thereby challenging drug development for AD.This study aims to screen high throughp...Objective Alzheimer's disease(AD)is the most common cause of dementia.The pathophysiology of the disease mostly remains unearthed,thereby challenging drug development for AD.This study aims to screen high throughput gene expression data using weighted co-expression network analysis(WGCNA)to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus(GEO)database.Normalization,quality control,filtration,and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules.Furthermore,the correlation coefiidents between the modules and clinical traits were computed to identify the key modules.Gene ontology and pathway enrichment analyses were performed on the key module genes.The STRING database was used to construct the protein-protein interaction(PPI)networks,which were further analyzed by Cytoscape app(MCODE).Finally,validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules,among which 6 modules were identified as the key module relating to AD occurrence.These key modules are primarily involved in chemical synaptic transmission(G0:0007268),the tricarboxylic acid(TCA)cycle and respiratory electron transport(R-HSA-1428517).WDR47,OXCT1,C3orfl4,ATP6V1A,SLC25A14,NAPB were found as the hub genes and their expression were validated by external datasets.Conclusions Through modules co-expression network analyses and PPI network analyses,we identified the hub genes of AD,including WDR47,0XCT1,C3orfl4i ATP6V1A,SLC25A14 and NAPB.Among them,three hub genes(ATP6V1A,SLC25A14,OXCT1)might contribute to AD pathogenesis through pathway of TCA cycle.展开更多
[Objectives]To explore the effect of total flavonoids from Phyllanthus emblica L.on tumor proliferation and immune function.[Methods]The effects of total flavonoids of P.emblica L.on the proliferation of 6 different t...[Objectives]To explore the effect of total flavonoids from Phyllanthus emblica L.on tumor proliferation and immune function.[Methods]The effects of total flavonoids of P.emblica L.on the proliferation of 6 different tumor cell lines(human hepatoma cell line HepG-2,human cervical cancer cell line Hela,human gastric cancer cell line SGC7901,human nasopharyngeal carcinoma cell line CNE-2,human lung cancer cell line H460 and human ovarian cancer cell line A2780)were compared by SRB method.The effect of total flavonoids from P.emblica L.on the proliferation of mouse lymphocytes induced by concanavalin(ConA)or lipopolysaccharide(LPS)in vitro was detected by CCK-8 method.[Results]The results of SRB assay showed that compared with the normal group,the total flavonoids of P.emblica L.had obvious inhibitory effect on 6 kinds of tumor cells.Among them,the inhibitory effect on H460 cells and CNE-2 cells was the most significant,and the IC50 was(471.36±50.66),(463.26±40.75)μg/mL,respectively.The high dose group of total flavonoids from P.emblica L.had the same inhibitory effect as the positive drug 5-Fu.The results of CCK-8 assay showed that compared with the blank group,the total flavonoids of P.emblica L.significantly inhibited the proliferation of mouse lymphocytes induced by ConA or LPS(*P<0.05,**P<0.01).[Conclusions]The total flavonoids of P.emblica L.had significant anti-tumor activity.展开更多
基金Supported by: the National Natural Science Foundation of China, No. 30560189the Grant from Innovation Groupfor Developing Chinese HerbsNew Drugsamong University Talents in Guangxi
文摘BACKGROUND: Modern pharmacological studies have demonstrated that Panax notoginseng saponins (PNS) can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer's disease (AD) remains unclear. OBJECTIVE: Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A. DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University. MATERIALS: Ninety healthy Wistar rats of both genders, 15-month-old (n =75) and 3-month-old rats as young controls (n =15), were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd (permission No. Z53021485, Yuxi, Yunan Province, China). Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science. METHODS: This study was performed at the Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each: model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose (5 mL/kg) every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μL ibotenic acid (5 g/L) bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were gavaged with 200 and 100 mg/kg PNS suspension, respectively. Huperzine A suspension (0.3 mg/kg) was used in the huperzine A group. Rats in the other 3 groups were gavaged with a corresponding volume of normal saline. In each group, administration was carried out once per day for 4 consecutive weeks. MAIN OUTCOME MEASURES: After administration, learning and memory abilities were measured by place navigation and spatial probe tests. Recording indices consisted of escape latency (time-to-platform), number of times to find the platform within 2 minutes, number of times the animal crosses the original platform location, and the percent of swimming time in each quadrant. RESULTS: Several rats died due to inflammatory reactions following brain lesion or intragastric administration; therefore, 61 rats were included in the final analysis. Results of spatial navigation test: Escape latency of rats in the model group was significantly prolonged, and number of times to find the platform within 2 minutes were significantly reduced compared with other groups (both P < 0.05). No significant differences in these two indices were measured among the administration groups (all P > 0.05). Results of spatial probe test: Times for crossing the original platform location and percent of time spent in the quadrant of original platform location were significantly less in the model group than in the other groups (P < 0.05). There were no significant differences in these two indices among the administration groups (P > 0.05). CONCLUSION: PNS can remarkably improve spatial learning and memory abilities of rats with AD. The therapeutic effect of PNS is not dose-dependent and is equivalent to the effect of huperzine A.
基金Fund supported by the National Natural Science Foundation of China(81460598 and 81660644)the Natural Science Foundation of Jiangsu Province(BK20170267)Guangxi Special Fund for the First-Class Discipline Construction Project(05019038).
文摘Objective Alzheimer's disease(AD)is the most common cause of dementia.The pathophysiology of the disease mostly remains unearthed,thereby challenging drug development for AD.This study aims to screen high throughput gene expression data using weighted co-expression network analysis(WGCNA)to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus(GEO)database.Normalization,quality control,filtration,and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules.Furthermore,the correlation coefiidents between the modules and clinical traits were computed to identify the key modules.Gene ontology and pathway enrichment analyses were performed on the key module genes.The STRING database was used to construct the protein-protein interaction(PPI)networks,which were further analyzed by Cytoscape app(MCODE).Finally,validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules,among which 6 modules were identified as the key module relating to AD occurrence.These key modules are primarily involved in chemical synaptic transmission(G0:0007268),the tricarboxylic acid(TCA)cycle and respiratory electron transport(R-HSA-1428517).WDR47,OXCT1,C3orfl4,ATP6V1A,SLC25A14,NAPB were found as the hub genes and their expression were validated by external datasets.Conclusions Through modules co-expression network analyses and PPI network analyses,we identified the hub genes of AD,including WDR47,0XCT1,C3orfl4i ATP6V1A,SLC25A14 and NAPB.Among them,three hub genes(ATP6V1A,SLC25A14,OXCT1)might contribute to AD pathogenesis through pathway of TCA cycle.
基金Supported by School-level Project of Guangxi University of Chinese Medicine(XP018091)Basic Ability Improvement Project of Young and Middle-aged Teachers in Colleges and Universities in Guangxi(2017KY0323).
文摘[Objectives]To explore the effect of total flavonoids from Phyllanthus emblica L.on tumor proliferation and immune function.[Methods]The effects of total flavonoids of P.emblica L.on the proliferation of 6 different tumor cell lines(human hepatoma cell line HepG-2,human cervical cancer cell line Hela,human gastric cancer cell line SGC7901,human nasopharyngeal carcinoma cell line CNE-2,human lung cancer cell line H460 and human ovarian cancer cell line A2780)were compared by SRB method.The effect of total flavonoids from P.emblica L.on the proliferation of mouse lymphocytes induced by concanavalin(ConA)or lipopolysaccharide(LPS)in vitro was detected by CCK-8 method.[Results]The results of SRB assay showed that compared with the normal group,the total flavonoids of P.emblica L.had obvious inhibitory effect on 6 kinds of tumor cells.Among them,the inhibitory effect on H460 cells and CNE-2 cells was the most significant,and the IC50 was(471.36±50.66),(463.26±40.75)μg/mL,respectively.The high dose group of total flavonoids from P.emblica L.had the same inhibitory effect as the positive drug 5-Fu.The results of CCK-8 assay showed that compared with the blank group,the total flavonoids of P.emblica L.significantly inhibited the proliferation of mouse lymphocytes induced by ConA or LPS(*P<0.05,**P<0.01).[Conclusions]The total flavonoids of P.emblica L.had significant anti-tumor activity.