检索结果-南通市图书馆

Down regulation of cyclooxygenase-2 is involved in delayed neuroprotec-tion by ischemic preconditioning in rats

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2005年第4期26卷 441-446页

作者： Liang XIAO Fei-li ZHAO Xing-zu ZHU~1 Department of pharmacology II,shanghai institute of materia medica,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 2.12.3,china Department of pharmacology II Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Aim:To examine whether the prostaglandins(PGs)pathway is involved in trigger-ing delayed neuroprotection by ischemic preconditioning(IPC)and evaluate theeffects of IPC on cyclooxygenase-2(COX-2)expression following focal cerebralischemia and reperfusion in ***:IPC was induced by 10 min of salineinfusion into the left internal carotid artery with the right common carotid arteryclamped at the same *** cerebral artery occlusion(MCAO)and reperfusionmodel was produced using intraluminal filament ***:IPC 48 h priorto MCAO significantly reduced infarct area as compared with MCAO *** inhibitor of COX indomethacin(3 mg/kg ip)applied 1 h prior to or 1 hafter IPC failed to affect its protective *** had no direct effect on thecortex COX-2 mRNA and protein expression 72 h later,but decreased the expres-sion of COX-2 mRNA and protein following ischemia and reperfusion ***:PGs pathways was not involved in triggering delayed neuroprotectionby IPC,and IPC induced down-regulation of COX-2 following focal cerebral is-chemia and reperfusion in rats in vivo.

关键词： ischemic preconditioning brain ischemia prostaglandins cyclooxygenase-2

Design,synthesis,antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2007年第1期28卷 140-152页

作者： Hai-hong LI~2 Xiu-hua ZHANG~3 Jin-zhi TAN~2 Li-li CHEN~2 Hong LIU~(2,5) Xiao-min LUO~(2,5) Xu SHEN~(2,4) Li-ping LIN~(3,5) Kai-xian CHEN~2 Jian DING~3 Hua-liang JIANG~(2,4)2 Center for Drug Discovery and Design,State Key Laboratory of Drug Research,shanghai institute of materia medica,shanghai institutes for biological sciences,and Graduate School,chinese academy of sciences,shanghai 2.12.3,china 3 division of anti-tumor pharmacology,shanghai institute of materia medica,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 2.12.3,china 4 School of Pharmacy,East china University of Science and Technology,shanghai 200237,china Center for Drug Discovery and Design State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences and Graduate School Chinese Academy of Sciences Shanghai China division of anti-tumor pharmacology Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China School of Pharmacy East China University of Science and Technology Shanghai China

Aim:To design and synthesize a novel class of antitumor agents,featuring the 3,5-substituted indolin-2-one ***:Based on enzyme binding fea-tures of（Z）-SU5402,introducing a β-pyrrole group at the 3-position of the indolin-2-one core,a series of novel 3,5-substituted indolin-2-ones were designed *** human carcinoma cell lines of A-43l,A-549,MDA-MB-468,and Autosomal Dominant Polycystic Kidney disease were chosen for the cellproliferation ***:Twenty new compounds（1a-t）with E configurationhave been designed,synthesized and *** structural features weredetermined by nuclear magnetic resonance（NMR）spectra,low-and high-resolu-tion mass spectra,and confirmed by X-ray *** the enzymeassay showed a weak inhibition effect against the epidermal growth factor receptor,vascular endothelial growth factor receptor,fibroblast growth factor receptor andplatelet-derived growth factor receptor tyrosine kinases,the cell-based antitumoractivity was *** 1 g and lh showed higher inhibitory activitytoward the A-549 and MDA-MB-468 cell lines with IC50of 0.065-9.4 μmol/***:This study provides a new template for further development ofpotent antitumor drugs.

关键词： protein-tyrosine kinase indolin-2-one antitumor drug screening assays drug design molecular models

Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2005年第8期26卷 952-958页

作者： Yong HUANG, Jing LIU, Li-zhen WANG, Wei-yu ZHANG, Xing-zu ZHU~1 Department of pharmacology, shanghai institute of materia medica, shanghai institutes for biological sciences, chinese academy of sciences, Graduate School of chinese academy of sciences, shanghai 2.12.3, china Department of pharmacology Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of Chinese Academy of Sciences Shanghai China

Aim: To establish an in vitro injured motor neuronal model and investigate the neuroprotective effects and possible mechanism of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on this model. Methods: After macrophages were stimulated with lipopolysaccharide (LPS)+interferon-γ(IFN-γ) in the pre-sence or absence of celecoxib for 24 h, the cell-free supernatant of LPS-stimulated macrophages was transferred to the culture of NSC34 cells. Viability of NSC34 cells was assessed by MTT assay after a further 24 h and 72 h incubation. After macrophages were stimulated by LPS+IFN-γ for 12 h or 24h, the release of pros-taglandin E2(PGE2), nitric oxide (NO), reactive oxygen species (ROS), tumor necro-sis factor α(TNF-α) and interleukin-1β (IL-1β) from macrophages was measured by radioimmunoassay, Griess assay, fluorescence assay and enzyme-linked immunosorbent assay, respectively. The mRNA levels of COX-2, inducible nitric oxide synthase (iNOS), TNF-α and IL-1β in macrophages were determined by reverse transcription-polymerase chain reaction after macrophages were stimu-lated for 6 h and 12 h. Results: The supernatant of LPS-stimulated mouse mac-rophages induced the death of NSC34 cells and celecoxib protected the NSC34cells against this toxicity. The LPS-induced increases in the release of PGE2, NO,TNF-α and IL-1β from macrophages were attenuated by pre-treatment with celecoxib. However, celecoxib showed no effect on the ROS levels upregulated by LPS+IFN-γin the macrophage supernatant. The mRNA levels of COX-2, iNOS, TNF-α and IL-1β were increased in LPS-activated macrophages and, except COX-2, reduced by pre-treatment with celecoxib. Conclusion: An in vitro injured motor neuronal model was established by using the toxicity of LPS-stimulated mouse macrophages toward motor neuronal NSC34 cells. In this model, celecoxib exerted neuroprotective effects on motor neurons via an inhibition of the neurotoxic secretions from activated macrophages.

关键词： amyotrophic lateral sclerosis celecoxib macrophage NSC34 cell lipopolysaccharide cyclooxygenase-2 prostaglandin E2 nitric oxide reactive oxygen species

Insulin-sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative in vitro

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2007年第3期28卷 417-422页

作者： Hao-shu WU~(2,4) Juan-hong YU~(3,4) Ying-yin LI~2 Yu-she YANG~3 Qiao-jun HE~2 Yi-jia LOU~(2,5) Ru-yun JI~3 ~2Department of pharmacology and Toxicology,College of Pharmaceutical sciences,Zhejiang University,Hangzhou 310058,china ~3State Key Laboratory of Drug Research,shanghai institute of materia medica,shanghai institutes for biological sciences,Graduate School of the chinese academy of sciences,shanghai 2.12.3,china Department of pharmacology and Toxicology College of Pharmaceutical Sciences Zhejiang University Hangzhou China Department of State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Graduate School of the Chinese Academy of Sciences Shanghai China

Aim:To examine the insulin sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative YY20 in insulin-sensitive cell ***:Theperoxisome proliferator-activated receptor γ（PPARγ）agonist bioactivities of YY20were detected by a preadipocyte differentiation ***-PCR and Westernblotting analysis were used to detect the expression of the target gene or *** effects of YY20 on insulin-mediated glucose consumption were determined inthe HepG2 human hepatocellular carcinoma ***:YY20 could enhancethe differentiation of preadipocytes to adipocytes and upregulate the gene ex-pression of PPARγ2,as well as the protein expression of insulin receptor sub-strate-1（IRS-1）,glucose transporter-4（GLUT4）,and adiponectin（ACRP30）.Theeffects on GLUT4 and ACRP30 could be reversed by the PPARγ inhibitor ***,YY20 efficiently reduced glucose consumptions in HepG2 cells after24 h culture,and the effects were related to insulin and YY20 ***:YY20,a potential insulin-sensitizing agent like rosiglitazone,couldenhance glucose consumption in HepG2 cells in a concentration-and insulin-dependent *** may improve the insulin resistance associated with type 2diabetes.

关键词： YY20 peroxisome proliferator-activated receptor y insulin sensitivity glucose consumption

Ohmefentanyl stereoisomers induce changes of CREB phosphorylation in hippocampus of mice in conditioned place preference paradigm

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Cell Research 2003年第1期13卷 29-34页

作者： CAN GAO, Li WEI CHEN, JIE CHEN, XUE JUN XU, ZHI QIANG CHISecond Department of pharmacology, shanghai institute of materia medica, shanghai institutes for biological sciences, chinese academy of sciences, shanghai 200031, chinaResearch Center for Biochemistry and Molecular Biology, Xuzhou medical College, Xuzhou, Jiangsu 221002, china Second Department of pharmacology Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China Research Center for Biochemistry and Molecular Biology Xuzhou Medical College Xuzhou China

The present study was designed to determine the changes of phosphorylation of cAMP- response element binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204) in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204 displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for a long time without affecting total CREB protein levels. The effect of F9204 was similar to morphine which effect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitive N-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phosphorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also the phosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterations in the phosphorylation of CREB be relevant to opiates signaling and the development of opiates depende

关键词： cAMP-response element binding protein (CREB) ohmefentanyl stereo isomers opiates hippocampus conditioned place preference (CPP).

Tetrahydroacridine inhibits voltage-dependent Na~+ current in guinea-pig ventricular myocytes

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2004年第9期 36-42页

作者： Wei WANG, Yi-ping WANG, Guo-yuan HUState Key Laboratory of Drug Research, The First Department of pharmacology, shanghai institute of materia medica, shanghai institutes for biological sciences, chinese academy of sciences, shanghai 2.12.3, china

AIM: To study the effects of tetrahydroacridine (tacrine) on voltage-gated Na+ channels in cardiac tissues. METHODS: Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltage-depe... 详细信息

关键词： Alzheimer disease cholinesterase inhibitors sodium channels tetrahydroacridine (tacrine) myocardium patch-clamp techniques

Pharmacokinetics of magnesium lithospermate B after intravenous administration in beagle dogs

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2004年第11期 18-23页

作者： Xiao-chuan LI, Chen YU, Wei-kang SUN, Gang-yi LIU, Jing-ying JIA, Yi-ping WANGDepartment of pharmacology, shanghai institute of materia medica, shanghai institutes for biological sciences, chinese academy of sciences, shanghai 2.12.3 Central Laboratory, shanghai Xuhui Central Hospital, shanghai 200002, china

AIM: To develop a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the phar-macokinetic study of magnesium lithospermate B (MLB), and study the pharmacokinetics of MLB after iv administration in beagle dogs. METHODS: Each beagle dog was iv administered MLB 3, 6, and 12 mg/kg random. The serum drug concentration was determined by specific liquid chromatography-tandem mass spectrometry (LC-MS/ MS) assays. The pharmacokinetic parameters were calculated by Drug and Statistics version 1.0 program. RESULTS: The calibration curve for MLB was linear over a range of 16-4096μg/L with coefficients of correlation >0.999. The intra- and inter-day precisions (CV) of analysis were 3 %. After iv administration of MLB at the doses of 3, 6, and 12 mg/kg, the C0 values for MLB were estimated to be of 24, 47, and 107 mg/L, respectively. The AUC increased with the increasing doses for iv administration, and the mean AUC0-t values were 109.3, 247.9, and 5

关键词： Salvia miltiorrhiza magnesium lithospermate B pharmacokinetics liquid phromatography-tandem mass spectrometry

Design,synthesis and antitumor evaluation of a new series of N-substi-tuted-thiourea derivatives

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2006年第9期27卷 1259-1271页

作者： Jian LI~2 Jin-zhi TAN~2 Li-li CHEN~2 Jian ZHANG~2 Xu SHEN~(2,3)Chang-lin MEI~(4,6)Li-li FU~4 Li-ping LIN~5 Jian DING~5 Bing XIONG~2 Xi-shan XIONG~4 Hong LIU~(2,6)Xiao-min LUO~(2,6)Hua-liang JIANG~(2,3)2 Drug Discovery and Design Centre,State Key Laboratory of Drug Research,shanghai institute of materia medica,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 2.12.3.china 3 School of Pharmacy.East china University of Science and Technology,shanghai 200237,china 4 division of Nephrology,Department of Internal Medicine,Changzheng Hospital,Second Military medical University,shanghai 200003,china 5 division of antitumor pharmacology,shanghai institute of materia medica,shanghai 2.12.3.china Drug Discovery and Design Centre State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China School of Pharmacy East China University of Science and Technology Shanghai China division of Nephrology Department of Internal Medicine Changzheng Hospital Second Military Medical University Shanghai China division of antitumor pharmacology Shanghai Institute of Materia Medica Shanghai China

Aim:To design and synthesize a novel class of protein tyrosine kinase inhibitors,featuring the N-(2-oxo-1,2-dihydroquinolin-3-yl-methyl)-thiourea ***:First,compounds 1 and 2 were identified using the virtual screeningapproach in conjunction with binding assay based on surface plasmon ***,3 regions of compounds 1 and 2 were selected for chemical *** compounds were characterized potent inhibitory activities toward thehuman lung adenocarcinoma cell line SPAC ***:Forty new compounds(1-2,3a-g,4a-w,and 5a-l)were designed,synthesized and *** com-pounds(1,3e,41,4w,5a,and 5b)were found to show promising inhibitory activityagainst the SPAC1 tumor cell *** inhibitory activity of compound 5aincreases approximately 10 times more than that of the original compound ***:This study provides a promising new template with potential antitu-mot activity.

关键词： N-substituted-thiourea derivatives antitumor SPAC1 tyrosine kinase inhibitor virtual screening

(5R)-5-hydroxytriptolide inhibits IFN-γ-related signaling

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2006年第12期27卷 1616-1621页

作者： Ru ZHOU~2 Jun-xia WANG~2 Wei TANG~2 Pei-lan HE~2 Yi-fu YANG~2 Yuan-chao LI~3 Xiao-yu LI~2 Jian-ping ZUO~(2,4)2 Laboratory of Immunopharmacology and 3 Laboratory of Chemistry,State Key Laboratory of Drug Research,shanghai institute of materia medica,shanghai institutes for biological sciences,chinese academy of sciences,shanghai 2.12.3,china Laboratory of Immunopharmacology State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China Laboratory of Chemistry State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Aim:(5R)-5-hydroxytriptolide(LLDT-8)displayed anti-arthritis and anti-allogenictransplantation rejection activities in our previous ***,we aim to furtherclarify the effect of LLDT-8 on the pro-inflammatory cytokine IFN-γ.Methods:Tcells were activated with anti-CD3 antibody or concanavalin A(ConA).The ex-pression of cell surface molecules was detected with flow *** werelabeled with carboxyfluorescein diacetate succinimidyl ester(CFSE)to test ***-γ production was determined by enzyme-linked *** proliferation was evaluated by[~3H]-thymidine *** wereimmunized with ovalbumin to assess the in vivo immune ***-PCR andReal-time PCR were applied to determine the mRNA *** protein phos-phorylation levels were detected by Western immunoblot ***:LLDT-8 at 100 nmol/L did not change the CD25,CD69,and CD154 expressions in anti-CD3-stimulated T ***-8 markedly blocked the cell division of CD4 andCD8 T cells after ConA ***-8 inhibited T cell-derived IFN-γ***,LLDT-8 suppressed the ovalbumin-specific T cell prolif-eration and IFN-γ *** anti-CD3-activated T cells,LLDT-8 abrogated themRNA expression of signal transducer and activator of transcriptionl(STAT1),T-box transcription factor,IL-12 receptor β2,STAT4,and interferon regulatory fac-tor 1 in the IFN-γ expression *** blot analysis showed that LLDT-8 blocked the phosphorylation levels of extracellular signal-regulated kinase,stress-activated protein kinase(SAPK)/c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase in anti-CD3 plus anti-CD28-activated T *** addition,LLDT-8 reduced the transcripts of macrophage inflammatory protein(Mip)-1α,Mip-1β,regulated upon activation normally T-cell expressed and secreted,induc-ible protein-10,IFN-inducible T cell a chemoattractant,and monokine induced byIFN-7 in IFN-γ-stimulated murine macrophage cell line Raw 264.7 ***:LLD

关键词： (5R)-5-hydroxytriptolide IFN-γ MAPK chemokine