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Acta Pharmacologica Sinica 2005年第11期26卷 1339-1344页

作者： hua sun, geng-tao liu~2 ~2 department of pharmacology, institute of materia medica, peking union medical college & chinese academy of medical sciences, beijing 100050, china department of pharmacology Institute of Materia Medica Peking Union Medical College & Chinese Academy of Medical Sciences Beijing China

Aim: To study the potential chemopreventive effect of dimethyl dicarboxylate biphenyl (DDB), an anti-hepatitis drug, on hepatocarcinogenesis in vitro. Methods: The anti-carcinogenesis effect of DDB was assessed on a two-stage chemical oncogenesis model induced by 3-methylcholanthrene and 12-0-tetradecanoyl phorbol 13-acetate (TPA) with WB-F344 rat liver epithelial cells (WB-F344 cells) in vitro. A soft-agar colony formation assay was used to determine the tumorigenic potential of the transformed WB-F344 cells. The gap junctional intercellular communication (GJIC) was detected using the scrape loading/ dye transfer technique. Results: DDB at 1 μmol/L, 2 μmol/L, and 4 μmol/L significantly prevented the malignant transformation of WB-F344 cells induced by 3-methylcholanthrene and TPA. The average number of transformed foci decreased dramatically by 10.0%, 37.2%, and 47.4%, respectively. In soft agar, a remarkable decrease in colony numbers was observed in transformed cells treated with 2 μmol/L and 4 μmol/L DDB. DDB at 1 μmol/L, 2 μmol/L, and 4 μmol/L inhibited the downregulation of GJIC induced by TPA in a dose-dependent manner. The GJIC recovered to 25.6%, 34.6%, and 44.9%, respectively, of the control WB-F344 cells by DDB. Conclusion: DDB has a potential chemopreventive effect on hepatocarcinogenesis induced by carcinogens in vitro.

关键词： dimethyl dicarboxylate biphenyl liver neoplasm: cell transformation chemoprevention epithelial cell gap junctions

Protective effects of compound FLZ onβ-amyloid peptide-(25-35)-induced mouse hippocampal injury and learning and memory impairment

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Acta Pharmacologica Sinica 2006年第6期27卷 651-658页

作者： Fang FANG geng-tao liu~2 department of pharmacology,institute of materia medica,peking union medical college and chinese academy of medical sciences,beijing 100050.china department of pharmacology Institute of Materia Medica Peking Union Medical College and Chinese Academy of Medical Sciences Beijing China

Aim:To study the protective effects of compound FLZ,a novel synthetic ana-logue of natural squamosamide,on learning and memory impairment and lesionsof the hippocampus caused by icv injection of β-amyloid25-35(Aβ25-35)in ***:Mice were icv injected with the Aβ25-35(15 nmol/mouse),and thentreated with oral administration of 75 mg/kg or 150 mg/kg of FLZ once daily for 16consecutive *** impairment of learning and memory in mice were testedusing step-down test and Morris water maze *** content of malondialdehyde(MDA)and the expressions of acetylcholinesterase(ACHE),Bax,and Bcl-2 in theCA1 region of the mouse hippocampus were measured by biochemical and immu-nohistochemical analysis,*** pathological damages of hippocam-pus were observed using a ***:FLZ(75 mg/kg,150 mg/kg)significantly attenuated Aβ25-35-induced impairment of learning and memory in thestep-down test and Morris water maze *** also reduced pathological dam-ages to the hippocampus induced by Aβ25-35Furthermore,FLZ prevented theincrease of AChE and Bax,and the decrease of Bcl-2 immunoreactive cells in theCA1 region of the hippocampus,and reduced the increase of MDA content in thehippocampus in mice injected with Aβ***:FLZ has protective ac-tion against the impairment of learning and memory and pathological damage tothe hippocampus induced by icv injection of Aβ25-35in mice.

关键词： FLZ Aβ25-35 intracerebroventricular injection hippocampus acetylcholinesterase Bax Bcl-2 malondialdehyde

Different effects of nine clausenamide ennatiomers on liver glutathione biosynthesis and glutathione S-transferase activity in mice

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Acta Pharmacologica Sinica 2006年第8期27卷 1024-1028页

作者： Yu-qun WU Li-de liu hua-ling WEI geng-tao liu~1 department of pharmacology,institute of materia medica,peking union medical college & chinese academy of medical sciences.beijing 100050.china department of pharmacology Institute of Materia Medica Peking Union Medical College & Chinese Academy of Medical Sciences Beijing China

Aim:To study the effects of nine synthetic clausenamide with different stereostructures on liver glutathione(GSH)biosynthesis and glutathione S-transferase(GST)activity in ***:The nine test compounds were racemic mixturesand their ennatiomers of clausenamide,neoclausenamide and *** were administered clausenamide 250 mg/kg once daily for 3 consecutivedays,ig,and were killed 24 h after the last *** mouse liver cytosol GSHand GST were determined with related biochemical ***:Nineclausenamides exhibited different effects on liver GSH and *** nineclausenamides,only(+)and(±)clausenamide markedly increased liver cytosolGSH *** mechanism of increasing liver GSH content of(+)clausenamideis mainly due to stimulating the key limiting enzyme γ-glutamylcysteine synthetase(γ-GCS)activity for GSH *** other test clausenamides had no sucheffect on liver *** of the nine clausenamides induced a significant increaseof GST ***:The effects of clausenamide ennatiomers on liverGST and GSH varied with the alterations of their spatial structures.(+)Clausena-mide stimulated liver GSH biosynthesis through enhancing γ-GCS activity.

关键词： clausenamide glutathione γ-glutamylcysteine synthetase glutathione S-transferase

High-throughput fluorescence polarization method for identifying ligands of LOX-1

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Acta Pharmacologica Sinica 2006年第4期27卷 447-452页

作者： Tian-tai ZHANG~2 Zhen-tai huaNG~3 Ying DAI~2 Xiu-ping CHEN~2 Ping ZHU~3 Guan-hua DU~(2,4) ~2National Centre for Pharmaceutical Screening,institute of materia medica,chinese academy of medical sciences and peking union medical college,beijing 100050,china:~3department of Natural Product Biosynthesis,institute of materia medica,chinese academy of medical sciences and peking union medical college,beijing 100050,china National Centre for Pharmaceutical Screening Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China department of Natural Product Biosynthesis Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Aim: To develop and optimize a competitive fluorescence polarization(FP)method,and use it as a high-throughput screening(HTS)assay for drug ***: Human lectin-like oxidized low-density lipoprotein receptor-1(hLOX-1)and oxidized low-density lipoprotein(oxLDL)were used to establish a high-throughput fluorescence polarization assay to screen ligands of human LOX-1. A96-well plate assay was performed with a fast plate reader. Three fluoresceinisothiocyanate-labeled hLOX-1 concentrations(100, 200, and 400 nmol/L)wereselected to be titrated by oxLDL(from 0.05 nmol/L to 100 μmol/L)in order to obtainoptimal reactive concentrations. The concentration of Me2SO used(0%, 1%, 3%,5%) and incubation time(15 min, 30 min, 1 h, 2 h)were optimized. The Z’factor wascalculated to estimate the quality of FP-based HTS. Results: Concentrations of200 nmol/L for human LOX-1 and 50 μmol/L for oxLDL were used in the actualassay. Concentrations of 0% to 5% Me2SO and different reaction times did notaffect the FP-based HTS. The Z’value was 0.66. By using this detection andscreening system, 12 700 compounds were screened and 3 ligands with an IC50ofless than 4.5 μmol/L were found. Conclusion: The established competitive FP-based assay is sensitive, stable, highly reproducible and robust, and suitable forHTS for ligands of the hLOX-1 receptor.

关键词： high-throughput screening fluorescence polarization assay LDL receptors oxidized low density lipoprotein

Rivastigmine inhibits voltage-activated potassium currents in rat hippocampal pyramidal neurons

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Rivastigmine inhibits voltage-activated potassium currents i...

2002全国青年药理学英文学术会议

作者： PAN Ya-Ping, XU Xiang-hua, WANG Xiao-Liang(department of pharmacology, institute of materia medica, peking union medical college & chinese academy of medical sciences, beijing 100050, china)

AIM: Rivastigmine is a new acetylcholinesterase (ACHE) inhibitor following tacrine and donepezil. It displays specificity for central ACHE. Potassium channels in the brain has been found in close relationship with learning and memory. While no research about the action of rivastigmine on central potassium currents has been reported up to date. In the present study, we examined the effects of rivastigmine on two main voltage-activated outward potassium currents including transient outward potassium current (I) and delayed rectifier potassium current (I) in rat hippocampal neurons. METHODS: Hippocampal

关键词： rivastigmine hippocampus pyramidal neurons potassium currents patch clamp technique

mRNA Expression Alteration of Inward Rectifier Potassium Channels in Rats Brain with Cholinergic Impairment

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mRNA Expression Alteration of Inward Rectifier Potassium Cha...

2002全国青年药理学英文学术会议

作者： XU Xiang-hua, PAN Ya-Ping, WANG Xiao-Liang(department of pharmacology, institute of materia medica, peking union medical college & chinese academy of medical sciences, beijing 100050, china)

AIM: Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by a slow, progressive decline in cognitive and memorial function. It has a high incidence rate in old population. Central cholinergic deficit and reduction of acetylcholine (Ach) have been much clarified in AD patients. Potassium channel is a kind of membrane ion channels which contains the most subtypes up to date. Each channel subtype has different effect on modulating and influencing cell functions. Central potassium channels have been shown close relationship with learning and memory. The dysfunction of central potassium

关键词： ibotenic acid ATP-sensitive potassium channel inward rectifier acetylcholinesterase

Echinacoside attenuates 6-hydroxydopamine-induced neurotoxicity in PC12 cells

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Echinacoside attenuates 6-hydroxydopamine-induced neurotoxic...

第二届世界天然药物和传统药物药理学学术会议

作者： Yue-hua WANG~(1,2),Shuo TIAN~2,Guo-Rong HE~2,Lian-hua FANG~2,Xiao-Ping PU~(1*),Guan-hua DU~(2*) (1.department of Molecular and Cellular pharmacology,School of Pharmaceutical sciences,peking University, beijing 100191,china 2.beijing Key Laboratory of Drug Target Identification and Drug Screening, institute of materia medica,chinese academy of medical sciences & peking union medical college, beijing 100050,china)

＜正＞AIM To investigate the effects and the underlying mechanism of Echinacoside（ECH） against 6-OHDA-induced injury in *** 6-OHDA was added to cultured PC12 cells after pretreatment for 1 h with different concentration of ECH or saline and co-incubated for another 24 *** evaluate the protective effects of ECH,the morphological change was observed by microscope,the viability of PC12 cells was assayed by MTT *** explore the mechanism of ECH against 6-OHDA neurotoxicity, the mitochondrial oxidation-reduction activity（REDOX）,mitochondrial membrane potential（△ψm）,reactive oxygen species（ROS） production,ATP level,cytochrome c release,the activity of caspase 3,and apoptosis in PC12 cells were *** 6-OHDA induced the decrease of cell viability,ROS generation increase,ATP content decrease,mitochondrial dysfunction,and mitochondria -mediated apoptosis in PC12 *** could attenuate 6-OHDA-induced neurotoxicity,inhibit the collapse of△ψm,reduce the mitochondrial *** also inhibited cyt c release and caspase 3 *** Our results indicate that ECH attenuates 6-OHDA-induced neurotoxicity through anti-oxidative and anti-apoptosis mediated by mitochondria.

关键词： echinacoside Parkinson’s disease 6-hydroxydopamine

Analgesic effect of Tibet medicine Stellera chamaejasme Limt

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Analgesic effect of Tibet medicine Stellera chamaejasme Limt

第三届中日双边药理学和临床药理学学术会议

作者： sun Fang-Yun~1 ZHANG Bin~2 ZHU Xiao-Ming~2 ZHU Shen-Yin~2 DU Guan-hua~2 (1.Tibet National college Medicine department,Xianyang 712082,china 2.institute of materia medica, chinese academy of medical sciences and peking union medical college,beijing 100050,china)

＜正＞AIM To study the analgesic effect of Tibet medicines,Stellera chamaejasme Limt,which can offer an experimentation basis for the study of Tibet medicine. METHODS Acetic acid-induced wring test and hot- plate test in mice were used to study the analgesic effect. RESULTS The *** Limt ethanol extract could increase pain-threshold induced by hot irritation, and prolong the swing-tail time by electricity stimulation of the *** wring responses by acetic acid were signifi- cantly suppressed by it by over 50%.CONCLUSION The *** Limt ethanol extract has obviously analgesic effects on pain by heat *** pain reac- tion induced by chemical stimulus is obviously relieved by *** Limt,and they are worth further study.

关键词： Tibet medicine Stellera chamaejasme Limt,analgesic effect

Histiocytoid Sweet’s syndrome in a chinese woman associated with pleuritis:a case report and observation of the treatment

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Histiocytoid Sweet’s syndrome in a Chinese woman associated...

The Second Eastern Asia Dermatology Congress(EADC2012)

作者： WANG tao XU Chen-chen ZHOU Xi-ping and liu Yue-hua department of Dermatology peking union medical college Hospital peking union medical college chinese academy of medical sciences beijing 100730 china

＜正＞Histiocytoid Sweet’s syndrome（HSS） is a recently described entity by Requena et al in 2005 which has clinical feature to typical Sweet’s syndrome but is distinguished by dermal infiltration of immature neutrophilic granulocytes, immunohistochemically,most cells of the infiltrate showed immunoreactivity for CD15,CD43,CD45,CD68,MAC-386,

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Involvement of brain serotonergic system in Ganoderma Lucidum Extraction induced sleep

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Involvement of brain serotonergic system in Ganoderma Lucidu...

中国药理学会第十次全国学术会议

作者： Xiang-Yu Cui~a,Su-Ying Cui~a,Guo-Rong He~b,Lian-hua Fang~b,Guan-hua Du~b,Yong-He Zhang~(*a) (a department of pharmacology,School of Basic medical Science,peking University,38 Xue YuanLu Rd,beijing 100191,china b Insitute of materia medica,chinese academy of medical sciences and peking union medical college,1 XianNongTan St,beijing 100050)

Our pervious study indicated that GLE(Ganoderma Lucidum Extract) may have benzodiazepine-like hypnotic activity to some *** china,Ganoderma lucidum has been used as a tranquilizing agent to treat insomnia for thousands of years,although its mechanism remains *** a traditional chinese herb preparation, GLE may regulate sleep through multi-pathway activation besides GABAergic system.

关键词： Ganoderma Lucidum Extract Hypnotic effects GABAergic System Serotonergic system