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The continuous sedative effects of a newly synthesized purine derivative WS070133:is there any difference from diazepam?

The continuous sedative effects of a newly synthesized purin...

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第二届世界天然药物和传统药物药理学学术会议

作者： Xiao-Yu BAI~1,Song WU~2,Ling-Hua HAO~2,Wei-Ku ZHANG~1,Xiao-Hua ZHANG~3,Guan-Hua DU~(1*) (1.Beijing Key Laboratory of Drug Targets Identification and Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 10050,China 2.State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Department of New Drug Research and Development, Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050,China 3.School of Pharmaceutical Sciences,Shandong University, Jinan 250012,China)

AIM In clinical practice,sedatives are expected to induce the continuum of *** firstly combined a series of behavioral animal models to evaluate a new sedative candidate named WS070133 whether owned the continuous sedative effects. METHODS We used the elevated plus maze test to examine the minimal sedation(anxiolysis);the locomotor activity,hole-board and pentobarbital sodium induced hypnosis tests to evaluate the moderate sedation(twilight sleep);the tail flick test to investigate thedeepsedation(analgesia);the loss of righting reflex test to observe the general *** influence of WS070133 on the memory and motor coordinationin normal mice was also *** determination of adenosine deaminase activity and adenosine level in the brain of mice as well as picrotoxin induced seizure testwere conducted to explore the *** WS070133 significantly increased the entries and time spent in open arms;reduced head tips and locomotor activity counts;shortened the time to sleep, prolonged the sleeping time in pentobarbital sodium treated mice;increased pain threshold of normal mice in tail flick test;exerted non-anesthesia effect in the loss of righting reflex *** contrary to diazepam,WS070133made no significant influence on the memory and motor coordinationlesion,did not protect miceagainst picrotoxin induced seizure,but inhibited adenosine deaminase activity and increased adenosine level in the cortex and hypothalamus of *** We firstly reported the continuous sedative effects from minimal sedation to deep sedation of ***070133 lacked some side effects of diazepam and the mechanism underlying sedation was associated with adenosine system.

关键词： WS070133 continuum of sedation side effects adenosine

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Protective effect of scutellarin on cerebral ischemia-reperfusion injury in rats

Protective effect of scutellarin on cerebral ischemia-reperf...

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第二届世界天然药物和传统药物药理学学术会议

作者： Jia-Qi SUN~1,You-Lan WANG~2,Lei WANG~1,Ya-Juan CHEN~1,Lin LI~3,Tao GUO~3, Chen QING~1,Wei-Min YANG~(1*) (1.School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University,Kunming 650500,China 2.Kunming Institute of Medical Science,Kunming 650011,China 3.First Affiliated Hospital of Kunming Medical University,Kunming 650032,China)

AIM To study protective effects of scutellarin（SCU）,a flavonoid from a traditional Chinese medicinal plant,on brain damage in rats after ischemia-reperfusion（I-R） injury,and to investigate different interventions of SCU and SCU time-effect *** Transient cerebral ischemia was induced by middle cerebral artery occlusion（MCAO） for 1 h followed by 24 h reperfusion in *** deficit scores and brain infarction volume were measured 24 h after reperfusion,histopathological changes for HE staining was observed to certify the protective effects of *** The neurological scores of SCU 45 mg·kg were significantly decreased compared to that in model *** infarct volume were significantly decreased by administration of *** edema volume of SCU 45 mg·kg group were significantly *** histopathological changes in each treated group of SCU were significantly gentler than model *** concentration of vWF in plasma was reduced while the concentration of t-PA was increased by administration of *** pre-treatment,post-treatment and treatment during I-R showed protection on brain I-R damage,of which the treatment during I-R was most *** protective effects of SCU on brain I-R injury were observed continuously 1 -7 d after SCU *** infarct volume of SCU 45 and 180 mg·kg group were significantly decreased on 1,3, 7 d after *** with the length of reperfusion,infarct area of SCU 45 mg·kg group and model group were all in a trend of *** SCU(45 - 180 mg·kg,iv)treatment showed significantly protective effect on cerebral I-R injury in rats by markly reducing the infarct range and neurological deficit *** pre-treatment,post-treatment and treatment during I-R reduced rat brain I-R *** rat cerebral I-R injury has a trend of restore,the protective effects of SCU 45 mg·kg on rat brain I-R injury were observed between 1 -7 d after SCU once treatment.

关键词： scutellarin middle cerebral artery occlusion ischemia-reperfusion injury infarct volume

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20(s)-protopanaxadiol inhibits multiple cancer related signaling pathway and suppresses tumor growth of to human colorectal cancer

20(s)-protopanaxadiol inhibits multiple cancer related signa...

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第二届世界天然药物和传统药物药理学学术会议

作者： Jian-Li GAO~1,En-Yi HUANG~2,Ke YANG~2,Gui-Yuan Lü~1,Tong-Chuan HE~2 (1.Zhejiang Chinese Medical University,Hangzhou 310053,China 2.Molecular Oncology Laboratory, Department of Surgery,University of Chicago Medical Center,Chicago,IL 60637,USA)

AIM 20（s） -protopanaxadiol（PPD） is the metabolites of Ginseng saponin,including in both American ginseng （Panax quinquefolius L.,Araliaceae） and Asian ginseng（Panax ginseng ***）.In our previous study,we demonstrated that ginsenoside Rg3（the glucoside of PPD） exhibited antiproliferative effects on HCT-116 cells and reduced the tumor size of nude mice implanted with the HCT116 *** subsequence study exposed that the anti-tumor proliferation effect of PPD was stronger than ginsenoside Rg3 in vitro,but little reporter was focus on the in vivo anticancer effect of *** investigation is attempted to get more proofs about the effects of PPD to human colorectal cancer in vivo and in vitro,as well as to expose the mechanisms of action resulted by PPD in human colorectal *** The cytotoxicity of PPD was determined using MTT and crystal violet *** cycle analysis was detected by flow cytometry（FCM） after propidium iodide（PI） fluorescence *** effects of PPD on colon cancer growth in vivo were determined using Xenograft Tumor Model combined with Xenogen Bioluminescence Imaging.A novel cell-based assay was used for monitoring the influence of PPD to multiple cancer related-cells signaling *** expression and activity of A kinase（PRKA） anchor protein 8（AKAPA8L） and phosphatidylinositol transfer protein,alpha（PITPNA）(target genes from pervious microarray data) were analyzed by PCR and RNA interference *** PPD inhibited growth and induced cell cycle arrest in HCT116 ***,PPD also inhibited tumor growth in athymic nude mice bearing HCT116 cells as xenograft. Treating with PPD(30 mg·kg ) for 1 -3 weeks could reduce the tumor size of nude mice implanted with the HCT116 cells. PPD also changed the expression of AKAPAL8 and *** assay indicated PPD significantly suppressed the signals of NF-κB, JNK and MAPK/ERK signaling *** These results suggest that AKAPAL8 and PITPNA maybe,in part, relat

关键词： ginseng 20(s) -protopanaxadiol human colorectal cancer

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Target cells and binding sites for immunomodulatory action of Lycium barbarum polysaccharides LBPF4-OL

Target cells and binding sites for immunomodulatory action o...

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第二届世界天然药物和传统药物药理学学术会议

作者： Yong-Xiang ZHANG~*,Xiao-Rui ZHANG,Wen-Xia ZHOU,Chun-Hui QI (Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China)

AIM Lycium barbarum *** a renowned Yin strengthening agent in traditional Chinese *** barbarum ***-protein complex is well-known for its immunoregulatory and antitumor ***4-OL is the glycan part of Lycium barbarum ***-protein complex fraction 4（LBPF4）.The purpose of this study was to identify the immune target cell and binding site of *** Miltenyi MicroBeads were used to purify the *** proliferation was analyzed with[H]TdR incorporation *** of T and B cells was analyzed by flow cytometry（FCM）.Cytokine concentration was determined by multiplex bead analysis or ***4 gene mutation mice C3H/HeJ,antibody block and biolayer interferometry（BLI） were used to verify the binding *** Lymphocyte proliferation assay indicated that LBPF4-OL could not induce T and B lymphocytes proliferation spontaneously,but B cell proliferation could take place in the presence of activated macrophages or *** analysis found that LBPF4-0L could not activate T and B cells when co-cultured with splenocyte for 24 h in vitro. But it significantly prompted CD86 and MHC-Ⅱmolecules expression on macrophage in *** assay showed that LBPF4-OL greatly increased the levels of TNF-αand IL-1βon macrophage *** bead analysis showed that LBPF4-OL induced IL-6,IL-8,1L-10 and TNF-αproduction in a concentration dependent manner,but had no effect on IL-2 and IL-13 *** possible binding sits of CD19 on B lymphocyte,TLR4,TLR2 and CR3 on macrophages were studied,and TLR4 as the binding site of LBPF4-OL was further verified in C3H/HeJ *** showed that LBPF4-0L obviously induced the proliferation of splenocyte and the secretion of TNF-αand IL-1βin macrophage from wildtype mice C3H/*** the proliferation of splenocyte from mutation mice C3H/HeJ reduced *** results showed that LBPF4-OL could bind directly with TLR4 in *** Both B lymphocytes a

关键词： Lycium barbarum L.polysaccharide macrophage T lymphocyte B lymphocyte TLR4

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Curcumin and its derivatives against chronic myeloid leukemia - from lead to candidates

Curcumin and its derivatives against chronic myeloid leukemi...

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第二届世界天然药物和传统药物药理学学术会议

作者： Jian-Hua XU,Li-Xian WU,Yan-Fang LIN,Yang LIU,Rui-Jia CHEN,Xiu-Wang HUANG,Yuan-Zhong CHEN (1.Department of Pharmacology,2.Department of Pharmacochemistry Fuijan Key Laboratory of Natural Medicine Pharmacology School of Pharmacy 3.Fujian Institute of Hematology,Union Hospital Fujian Medical University,Fuzhou,China)

AIM Curcumin（Cur） a natural phenolic compound,is the major component of *** improve the its bioavailability, we synthesized series derivatives and investigated the activity of Cur and its derivatives against chronic myeloid leukemia （CML）.METHODS CML cell line K562 was used to investigate the effects of Cur and its derivatives and their mechanisms against CML;cell proliferation was assay by MTT;kinase assay by luminescence was used to test BCR-ABL kinase activity;Western blot was performed to test protein level of signal molecules;immunoprecipitation was used to test the co-chaperone complex of *** Cur was a potent inhibitor of proliferation of K562 cells with low toxicity to normal marrow mononuclear cells,and induced cytosolic accumulation of cytochrome c and activities of caspase 3,triggering apoptosis of K562 *** treatment produced a dose dependent increase in G/G phase and decrease in G/M phase,consistent with this,cyclin D1,cyclin B1 was deregulated in a dose dependent *** inhibited the proliferation and induced apoptosis of K562 cells was correlated with down-regulation of P210 and inhibition of tyrosine kinase activity of P210 without influence on bcr-abl mRNA level,moreover,Ras/MEKK/ SEK/JNK/c-Jun signal transduction pathway were also inhibited by Cur.A mechanistic explanation for these findings was provided in a subsequent study in which it was shown that down-regulation of P210 by Cur involves dissociation of the binding of P210 with Hsp90/p23 *** effects were observed as combination of Cur and Gleevec on both K562 cells and Gleevec resistant K562/G01 cells.C0806 is one of the derivatives serving as a Cur *** showed no spontaneous hydrolysis at pH 7.4,but was susceptible to hydrolysis and release Cur by homogenized liver and blood ***-MS analysis showed that the t and AUC of Cur released by C0806 in plasma were 10- and 20-fold higher than those of Cur,*** characteristics result

关键词： curcumin curcumin derivative chronic myeloid leukemia P210bcr/abl HSP90

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JTN,an α-glucosidase inhibitor from Bombyx mori excreta exerts hypoglycemic effects and improves beta cell dysfunction in the IGT mouse models

JTN,an α-glucosidase inhibitor from Bombyx mori excreta exe...

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第二届世界天然药物和传统药物药理学学术会议

作者： Quan LIU Shuai-Nan LIU Su-Juan SUN Zhu-Fang SHEN (Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Diabetes Research Center of Chinese Academy of Medical Sciences Beijing 100050 China) Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Bioactive Substances and Functions of Natural MedicinesDiabetes Research Center of Chinese Academy of Medical SciencesBeijing 100050China

＜正＞AIM To evaluate the impact of JTN on beta cell function in mice with impaired glucose tolerance（IGT）. METHODS Two animal models with IGT were chosen to evaluate the effect of JTN on beta cell *** MSG obese mice were induced with L-sodium glutamate,which have certain features of prediabetes,such as obesity,impaired glucose tolerance,beta cell *** mice characterized with impaired glucose tolerance and moderately *** of two IGT mouse models were randomly divided into five *** groups of IGT mice（n = 10） were fed for 45 d either a 50%sucrose diet（control） or a 50%sucrose diet supplemented with JTN 8,12,16 g or acarbose 0.3 g per kilogram *** glucose tolerance test（OGTT） and insulin tolerance test were *** plasma glucose,TG,TCHO and insulin level were measured at the end of the supplementation. Blood pressure and cataracta of eyes in MSG mice were *** beta cell function was quantified using a hyperglycemic *** After 7 weeks of supplementation,JTN flatted blood glucose peak and reduced the AUG during OG’IT compared with the control ***-βindex was significantly higher in JTN *** supplementation of JTN improved insulin sensitivity in both MSG and KKAy *** also decreased the fasting plasma glucose and *** hyperglycemic clamps,JTN increased glucose infusion rate（GIR） with dose-dependent fashion in MSG and KKAy mice,which indicated the improved beta cell insulin secretory *** the end of experiment,JTN also reduced the incidence of cataract in MSG *** These results suggested that JTN showed beneficial effect on glucose,lipid metabolism and the diabetic complication which were due to the improvement in insulin sensitivity and beta cell function.

关键词： Bombyx mori excreta impaired glucose tolerance beta cell function hyperglycemic clamp

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Primary study on the comparison of the two methods of serum pharmacology

Primary study on the comparison of the two methods of serum ...

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第二届世界天然药物和传统药物药理学学术会议

作者： Dan LI Jin-Cai HOU Cheng-Ren LIN Lei LI Jian-Xun LIU Experimental Research Center Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China

AIM To explore the different effect on endothelial cell by two methods of serum pharmacology , which are normal serum and model *** Normal and model serum obtained from normal mini-swine and coronary heart disease (CHD)mini-swine ***-swine were fed with high fat forage for 10 weeks and the coronary left anterior descending branch was injured by balloon intervention technique after 2 week feeding to establish CHD *** normal group were fed with common forage and not to do *** endothelial cell derived from normal mini-swine coronary arteries (Coronary arterial endothelial cells,CAEC).They were cultured in the presence of oxidized low-density lipoprotein (ox-LDL) by 50, 100 and 200 mg· L-1 for 24 h; and injured by hypoxia 2, 4 and 6 h/reoxygenation 24 h model (H/R), or neither (control).The cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction *** levels of lactate dehydrogenase (LDH), creatine kinase(CK), nitric oxide (NO) were determined by biochemical *** levels of endothelin-1 (ET-1) were detected by *** As compared with cells in the control group, on H/R injury and ox-LDL injury, cell vitality and NO were decreased,LDH, CK and ET-lwere *** with normal serum, the model serum on H/R injury CAEC,cell vitality was more decreased (P < 0.05) ; LDH, CK were more increased (P < 0.05) ; on ox-LDL injury CAEC, cell vitality and NO were more decreased (P < 0.05).ET-1 were more increased (P < 0.05).CONCLUSION Significant difference existed between the role of the two methods of serum pharmacology.

关键词： serum pharmacology normal serum model serum

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Cardioprotective effect of organic acids in Fructus Choerospondiatis on myocardial ischemia-reperfusion injury

Cardioprotective effect of organic acids in Fructus Choerosp...

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第二届世界天然药物和传统药物药理学学术会议

作者： Xi-Lan TANG~(1,2),Jian-Xun LIU~(1*),Wei DONG~2,Peng LI~1,Lei LI~1 (1.The Experimental Research Center,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China 2.Beijing University of Chinese Medicine,Beijing 100029,China)

AIM To investigate the effect of citric acid and L-malate,two main components of Fructus Choerospondiatis,on myocardial ischemia-reperfusion（I-R） injury and the underlying *** Rats were pretreated with citric acid and L-malate(0.5 and 0.25 g·kg) in 3 consecutive days,*** 1h after the last administration,rats were subjected to 40 min ischemia by occluding the left anterior descending coronary artery and 120 min *** infarct size,serum levels of tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6）,the maximum platelet aggregation rate were ***,the direct effects of citric acid and L-malate against cardiomyocyte necrosis and apoptosis were investigated in in vitro *** the presence of citric acid,L-malate(200,100 and 50 mg·L ) and diltizem(45 mg·L ),a positive control,neonatal rat cardiomyocytes were subjected to 3 h hypoxia followed by 2 h reoxygenation for necrosis（valued with the release of LDH in the culture medium） or 6 h reoxygenation for apoptosis studies（valued with flow cytometry ）.RESULTS We found that pretreatment with citric acid and L-malate(0.5 and 0.25 g·kg ) significantly reduced myocardial infarct size,the maximum platelet aggregation rate and the serum level of TNF-α（P<0.05 or P<0.01）,but not significantly reduced that of *** vitro experiments revealed that after 3 h hypoxia followed by 2 h reoxygenation（H-R） injury,the LDH levels were markedly increased in the medium of *** contrast, citric acid and L-malate(200 mg·L) treatment significantly reduced LDH release compared with the HR group（P<0.05 or P<0.01）.The apoptosis rate of HR-induced cardiomyocytes significantly increased,whereas treatment with citric acid and L-malate(400 and 200 mg·L ) significantly reduced the rate of apoptosis in cells（P<0.05 or P<0.01）.CONCLUSION Our results demonstrate citric acid and L-malate play a pivotal role in the protection on myocardial I-R injury,which is possible due to the

关键词： organic acids Fructus Choerospondiatis myocardial reperfusion injury citric acid L-malate

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Compound T-856 extends lifespan of the Nematode Caenorhabditis elegans

Compound T-856 extends lifespan of the Nematode Caenorhabdit...

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第二届世界天然药物和传统药物药理学学术会议

作者： Ai-Jun DING Shan-Qing ZHENG Qin-Li WAN Huai-Rong LUO State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China Graduate University of Chinese Academy of Sciences Beijing 100039China State Key Laboratory of Phytochemistry and Plant Resources in West ChinaKunming Institute of BotanyChinese Academy of SciencesKunming 650201China

AIM The goal of the study is to find compounds from natural products especially traditional Chinese medicines (TCM) that would increase the lifespan of Caenorhabditis elegans(***).METHODS The strains used in this study were wild-type N2 and TJ356 (DAF-16 : GFP).Compounds (0.5 mmol· L-1,0.05 mmol· L-1) extracted from TCMs were added directly to the top of NGM agar plates (3.5 mmΨ) containing 44 mmol-L-1 fluoredeoxyuridine (FUdR).*** OP50 was heat-killed at 65℃ for 30 *** synchronized L4 N2 worms (defined as day 1) were transferred to plates containing various concentrations of *** measurements of lifespan, hermaphrodites were analyzed every day from day 3 until *** that did not move when gently prodded were scored as *** and ruptured animals were *** the mean lifespan and maximum lifespan were *** analysis of the subcellular localization of DAF-16, synchronous IA TJ356 were transferred to plates containing compounds, for at least 1 h at 20℃ prior to analysis by fluorescence *** The Compound T-856 could extend the lffespan of C *** mean lifespan and maximum lifespan of C elegans could be extended by 16% andl7.8%.T-856 promoted DAF-16 translocation into the *** The Compound T-856 had anti-aging function, possibly by acting on insulin/IGF-1 signaling pathway.

关键词： natural products lifespan C.elegans Compound T-856

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Exploring therapeutic potential of FTY-720 for treating cardiac hypertrophic remodelling

Exploring therapeutic potential of FTY-720 for treating card...

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第二届世界天然药物和传统药物药理学学术会议

作者： Xin WANG Ming EEI Wei LIU Min ZI Ronald NAUMANN Rui-Ping XIAO Ludwig NEYSES R.John SOLARO Yun-Bo YE Elizabeth J.CAR TWRIGHT Faculty of Life Sciences Manchester Academic Health Sciences CentreThe University of ManchesterUK Max Planck Institute of Molecular Cell Biology and GeneticsGermany Institute of Molecular MedicinePeking UniversityBeijing 100871China Department of Physiology and Biophysics and Centre for Cardiovascular ResearchUniversity of Illinois at ChicagoUSA

AIM Cardiac hypertrophy is regarded as a clinical determinant of heart *** average age of cardiac hypertrophy onset is about 50 years old and the average patient with heart failure is 77 years *** leaves a relatively large time window where a patient displaying early cardiac hypertrophy could be treated to slow or even prevent the progression of hypertrophic remodelling; therefore studies to discover regulatory mechanisms underlying hypertrophic remodelling and to identify potential therapeutic targets for treating heart failure are of paramount *** Over the past few years using genetically modified mouse models and pharmacological agents our group has investigated the roles of a number of intracellular signalling proteins in cardiac hypertrophy, and recently identified a novel anti-hypertrophic molecule, p21-activated kinase-1 (Pak-1).RESULTS In the heart our studies demonstrate Pakl protection against stress-induced hypertrophic remodelling and targeting of Pak-1 in heart muscle by FTY-720 via Gi coupled sphingosine receptors is able to prevent the induction of stress-induced hypertrophy and reserve existing hypertrophy and fibrosis in wild-type mice, without compromising the cardiac functions.1FTY-720 is known as a sphingosine-like analogue, derived from myriocin, a component of the natural product Isaria *** Our data provides a scientific basis of development of FTY-720 for clinical applications in the treatment of cardiac hypertrophic remodelling.

关键词： FTY-720 p21-activated kinase-1 cardiac hypertrophy heart failure

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