检索结果-南通市图书馆

Effect and mechanism of LW-AFC on chronic unpredictable mild stress-induced mood and cognition impairment of mice

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2018年第4期32卷 344-345页

作者： Ming-hao ZHU wen-xia zhou Ning JIANG Institute of Pharmacology and Toxicology Beijing 100850 China State Key Laboratory of Toxicology and Medical Countermeasure Beijing 100850 China Nanjing University of Chinese Medicine Nanjing 210046 China

OBJECTIVE To explore the effect and mechanisms of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on chronic unpredictable mild stress(CUMS)-induced mood and cogni.tion impairment in mice.METHODS C57 BL/6 J mice were randomly placed into seven groups(n=10):normal control group,CUMS group,Fluoxetine(10 mg·kg^(-1),once per day) group,Liuwei Dihuang decoction group(LW,10 g·kg^(-1),once per day),and LW-AFC(0.8 g·kg^(-1),1.6 g·kg^(-1),3.2 g·kg^(-1),once per day) group.The stressed group was given CUMS for 4 weeks to set up a chronic multiple-stressed model.LW and LW-AFC was oral administered a week prior to CUMS and until the end of the study(a total of 35 d),while fluoxetine was administrated orally for 4 weeks.The anxiety behavior was analyzed using the open field test(OFT) and elevated plus maze test(EPM).The depression behavior was ana.lyzed using the sucrose preference test(SPT) and forced swimming test(FST).Spatial cognition was evaluated using Morris water maze(MWM) test and working memory was evaluated using new object recognition test(NORT).RESULTS CUMS for 28 d increased depressive-and anxiety-like behaviors.LW-AFC(1.6 g·kg^(-1)) significantly increased the numbers of entries into the open arm and time in the open arm of CUMS mice(P<0.05).LW-AFC(3.2 g·kg^(-1)) increased sucrose consumption and de.creased the immobility time of FST(P<0.01) of CUMS mice.The MWM test showed that spatial learning andmemory in CUMS mice were remarkably affected relative to controls,whereas LW-AFC(3.2 g·kg^(-1)) im.proves cognitive functions(P<0.05).CONCLUSION The mood and theability of learning and memory of thestressed group can be affected after exposure to CUS.Oral administration of LW-AFC significant.ly improved CUMS-induced impairments of mood and cognition in mice.

关键词：六味地黄汤中医治疗方法临床分析

Design and synthesis of 3＇-(prop-2-yn-1-yloxy)-biphenyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2016年第6期27卷 961-963页

作者： Jia-Kuo Liu Wei Gu xiao-Rui Cheng Jun-Ping Cheng Ai-Hua Nie wen-xia zhou Beijing Institute of Pharmacology and Toxicology Beijing 100850 China

Based on the lead compounds 1 and 2, a series of novel BACE1 inhibitors were designed and synthesized,among which compound 9h exhibited a 60 fold improvement in potency over the lead compound 1. This represents a good lead for the discovery of more promising BACE1 inhibitors for the potential treatment of AD. The result also showed that the prop-2-yn-1-yloxy is a suitable fragment for modification of cyclic acylguanidine BACE1 inhibitors.

关键词： Alzheimer’s disease BACE1 inhibitor Prop-2-yn-1-yloxy Cyclic acylguanidine

Design and synthesis of 5-cyclopropyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2016年第10期27卷 1626-1629页

作者： Jia-Kuo Liu Wei Gu xiao-Rui Cheng Jun-Ping Cheng Ai-Hua Nie wen-xia zhou Beijing Institute of Pharmacology and Toxicology Beijing100850China

By taking compound 1 as a lead, a series of 5-cyclopropyl substituted cyclic acylguanidine compounds were designed and synthesized as BACE1 inhibitors, compound 4d exhibited 84-fold improved inhibition efficiency than lead compound 1. The diphenyl fragment at the P3 position and the substituents at the second phenyl ring were essential for the compounds to achieve improved inhibition efficiency. This SAR studies provides new insights into the design and synthesis of more promising BACE1 inhibitors for the potential treatment of AD.

关键词： Alzheimer＇s diseaseBACE inhibitor SecretaseDrug discoveryCyclic acylguanidine

Design and synthesis of cyclic acylguanidines as BACE1 inhibitors

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2015年第10期26卷 1327-1330页

作者： Jia-Kuo Liu Wei Gu xiao-Rui Cheng Jun-Ping Cheng wen-xia zhou Ai-Hua Nie Beijing Institute of Pharmacology and Toxicology

Based on the lead compound 1 reported in literature, a series of novel BACE1 inhibitors were designed and synthesized, among which compound 11 exhibited a 14-fold improvement in potency over the lead compound 1. This ... 详细信息

关键词： Alzheimer’s disease BACE1 inhibitor Cyclic acylguanidine

LW-AFC and its active components ameliorate corticosterone-induced long-term potentiation impairment in mice

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2017年第10期31卷 989-990页

作者： Yan HUANG Dong LI wen-xia zhou Yong-xiang ZHANG State Key Laboratory of Toxicology and Medical Countermeasures Beijing 100850 China Department of TCM and Neuroimmunopharmacology Beijing Institute of Pharmacology and Toxicology Beijing 100850 China

OBJECTIVE LW-AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang Decoction.Previous studies have showed that LW-AFC could improve learning&memory ability in amny animal models.In this study,we focused on evaluating the effect of several main active components fromLW-AFC(B-B;loganin,LOG;morroniside,MOR;paeoniflorin,PF and stachyose,STA)on LTP.METHODS In vivo recording of LTP was used in this study to evaluate the effects of LW-AFC and it′s active components on coticorsterone(Cort)induced LTP impairment.RESULTS The results showed that LW-AFC could ameliorate Cort-induced LTP impairment.The effect of LW-AFC was abolished when the immune function was inhibited.Single administration(ig,ip,icv)of any of the components had no effect on Cort-induced LTP impairment.Consecutively intragastric administration or intraperitoneal injections(chronic administration)of B-B,LOG,MOR or PF for 7 d showed protective effect on Cort-induced LTP impairment.Intragastric administration of STA for 7 d protected LTP from impairment induced by Cort,while there was little improving effect when STA was administrated via intraperitoneal injection.In addition,when the intestinal microbiota was disrupted by applying the antibiotic cocktail,STA showed little protective effect against Cort.CONCLUSION In conclusion,LW-AFC and it′s components showed positive effects against cort induced LTP impairment,it seems that all displayed protective effects via indirectly,immune modulation might be the common pathway for all components;the exact pathways are different in each component,B-B,LOG,MOR and PF could be absorbed into the bloods tream and then modulate the peripheral immune function,while STA could not be absorbed and modulates the immune function via modulating intestinal microbiota.Further studies are needed to invesgate the underlying mechanisms and the synergetic effects of all components.

关键词： LW-AFC active components synaptic plasticity long-term potentiation intestinal microbiota

Neural stem cells derived from sporadic Alzheimer disease iPSCs exhibit excessive cell apoptosis and premature neuronal differentiation

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2018年第4期32卷 335-336页

作者： Lin ZHANG Ning JIANG wen-xia zhou Yong-xiang ZHANG Institute of Pharmacology and Toxicology Beijing 100850 China State Key Laboratory ofToxicology and Medical Countermeasures Beijing 100850 China School of Life Science and Biopharmaceutical Sciences Shenyang Pharmaceutical University Shenya

OBJECTIVE To establish an in vitro cell model based on patient-specific human neural stem cells to study the pathomechanism of sporadic AD as well as screen candidate drugs.METHODS The peripheral blood cells from sporadic AD patients and cognitive normal controls were repro.grammed into inducedpluripotent stem cells(iPSCs),which were further induced into neural stem cells and neurons.The cell growth curve during the differentiation process was recorded by the IncuCyte ZOOM,and neural stem cells and neurons were identified by immunofluorescence.The apoptosis of neural stem cells and neurons was detected by Click-iT~Plus TUNEL Assay.RESULTS Neural stem cells derived from AD patients and cognitive normal controls can express neural stem cell markers Nes.tin,Sox1,Sox2 and Ki67.TUNEL assay results showed that the number of TUNEL-positive cells in neu.ral stem cells derived from AD patients was significantly higher than that of cognitive normal controls(P<0.01).When neural stem cells were differentiated into neurons,the percentage of MAP2 positive cells in the neural stem cell-derived culture dish of AD patients was significantly higher than the cogni.tive normal controls at day 16 of neuronal differentiation(P<0.01);the TUNEL assay showed that the number of TUNEL-positive cells in AD-derived neurons was significantly greater than that in cognitive normal controls(P<0.01) at day 16 of neuronal differentiation.CONCLUSION Our study revealed that AD-iPSC-derived neural stem cells exhibit premature neuronal differentiation and increased neural apoptosis,which might be relevant to the neuronal loss of AD,thus may provide valuable new tools to screen candidate drugs for the disease and to discover the mechanisms underlying AD pathogenesis.

关键词：神经干细胞神经元临床分析治疗方法

Effects of Liuwei Dihuang decoction and its compatible prescriptions on the function of hypothalamus-pituitary-adrenal axis in senescence-accelerated mouse

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2015年第S1期29卷 74-75页

作者： Ning JIANG Si-di LI wen-xia zhou Yong-xiang ZHANG Beijing Institute of Pharmacology and Toxicology China Beijing 100850

OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-xie(three eliminators)components on the function of HPA axis.METHODS Male SAM-resistance/1(SAMR1)and SAM-prone/8(SAMP8)at the ages of 6and 12 months old were used.SAMP8 were orally administered with LW,three tonics and three eliminators at the doses of 10,6.4and 3.6g·kg-1·d-1,respectively,for consecutive 60 d.Serum level of CORT was assayed with ELISA method.The levels of hypothalamic CRH and pituitary ACTH was determined with radioimmunoassay.RESULTS The levels of hypothalamic CRH,pituitary ACTH and serous CORT were much higher in 6 and 12 months old SAMP8 than those in age-matched SAMR1,which suggested the abnormal function of HPA axis in SAMP8.Oral administration of LW and three tonics significantly decreased the level of hypothalamic CRH of 6 and 12 months old SAMP8,and reduced the levels of pituitary ACTH and serous CORT of 6 month old SAMP8.Three eliminators significantly decreased the level of hypothalamic CRH of 6 months old SAMP8.The results indicated that oral administration of LW,three tonics and three eliminators improved the function of HPA axis of SAMP8.CONCLUSION The results showed the hyperactivity of HPA axis of SAMP8,and LW improved the hyperactivity of 6 month old SAMP8.Three tonics and three eliminators had similar effects as LW,which had better effect after compatibility.

关键词： Liuwei Dihuang decoction senescence accelerated mo

Construction of NIM sub-network regulated by Liuwei Dihuang decoction and its characteristics

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2018年第4期32卷 306-307页

作者： Tong-xing WANG Lu HAN xiao-rui CHENG wen-xia zhou Yong-xiang ZHANG Beijing Institute of Pharmacology and Toxicology Beijing 100850 China The State Key Laboratory of Toxicology and Medical Countermeasures Beijing 100850 China

OBJECTIVE To construct the neuroendocrine immunomodulation(NIM) sub-network regulated by Liuwei Dihuang decoction(LW) and analyze its characteristics.METHODS We took the GSE57273 in GEO database and screened the differentially expressed genes(DEGs)(P10).Among them,there were 19 NIM signaling molecules in which only ESR1 changed significantly and 3 non-DEGs(NFATC2,RARA,TP53).However,the down.stream of the hub nodes were significantly changes.CONCLUSION The results suggested that LW might mainly regulate the non-hub nodes to recovery of the network imbalance of the body in the state of disease.

关键词：六味地黄汤神经内分泌治疗方法临床分析

Immunopotentiating activities and TLR4/MAPK related molecular mechanisms research of Lycium barbarum polysaccharide

在线全文

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2018年第4期32卷 263-264页

作者： xiao-rui ZHANG Ying-jie LI Chun-hui QI wen-xia zhou Yong-xiang ZHANG State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology Beijing China

OBJECTIVE To observe the effect and molecular mechanisms of Lycium barbarum polysaccharide(LBP) and glycopeptides on T,B lymphocytes and macrophages.METHODS ~3H-TdR incorporation method was used to compare the effects of LBP and glycopeptides on the proliferation lymphocytes.Peritoneal macrophages induced by sodium thioglycolate were used to compare the effects of LBP and glycopeptides.T and B lymphocytes were purified by immunomagnetic beads method.Using antibody blocking methods screening polysaccharide activity related receptors.C3H/HeJ mice were further used to observe the activity of LBP.Biolayer interference method was used to observe the binding kinetics of LBP with TLR4 in vitro.TLR4 level was tested by flow cytometry.Western blotting was used to observe the phosphorylation of p-38,SAPK/JNK and ERK.RESULTS The monosaccharide compo.sition of LBP is rhamnose,arabinose and galactose,and does not contain amino acids.The mixed lymphocyte proliferation experiment showed that LBP had more obvious effect on the proliferation of B cells,and glycosides induced T cells proliferation was more obvious.On the purify lymphocytes,it was found that LBP-induced B cells proliferation requires the involvement of macrophages.Further research found that anti-TLR4 antibody had significant inhibitory effect on LBP-induced macrophage release of TNF-α and IL-1β but not the anti-CR3 treatment.C3 H/HeJ mice related results further demonstrated that TLR4 is necessary for LBP activity.Although biolayer interference showed no obvious binding of TLR4/MD2 with LBP,flow cytometry confirmed that LBP could increase TLR4 expression.Western Blot experiments showed that the effect of LBP on macrophage was related to its activation of p-38/MAPK pathway and inhibition of ERK/MAPK and JNK/MAPK pathways.CONCLUSION TLR4 is the activity related receptors of LBP.LBP cannot directly bind to TLR4/MD2 complex in vitro,but can increase TLR4 expression and activate macrophage p-38/MAPK signaling pathway,inhibiting ERK-MAPK and JNK-MAPK signaling pathways.

关键词：枸杞多糖糖肽淋巴细胞治疗方法