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PF11 protects neuronal function from alcohol induced neuroinflammation-oxidative stress in the adult rat following a 4-day binge ethanol exposure

PF11 protects neuronal function from alcohol induced neuroin...

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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： Ya-Nan ZHAO,Fang WANG,Xiao-Mei HU,Wei ZHANG,Hui-Li WENG,Yi-Fei XU, Jing-Yu YANG,Chun-Fu WU~* (Department of Pharmacology,Shenyang Pharmaceutical University,Shenyang 110016,China)

AIM Pseudoginsenoside-F11(PF1l),an ocotillol-type saponin existing in American ginseng,can inhibit the ethanol -induced neuronal damage in vitro in our previous *** further investigate the effects of PF11 on alcoholism and the underlying mechanisms,we examined the effects of PF11 on neuronal function in the adult rat following a 4-day binge ethanol *** Sprague-Dawley rats were pretreated with PF11 or vehicle for 7 d,then a 4 d binge concurrent with PF11 or vehicle treatment was *** hour after last ethanol treatment,neuronal activity and ultrastructure were investigated by Fluoro-Jade B staining and electron microscopy,microglial and astrocyte response were assessed by immunohistochemistry,MDA and 3NT production of oxidative stress were detected by biochemical kits and western *** last,learning and memory abilities were explored by Morris water maze and novel object recognition test following 4 d of ethanol *** Pre-treatment with PFl 1 protected against ethanol -induced neurodegeneration,reduce microglial and astrocyte response and MDA and 3NT *** more,neuroprotective effects of PF11 were accompanied by prevention of deficits in spatial reversal learning ability and object recognition *** The results of the present study suggest an involvement of regulation of neuroinflammation-oxidative stress in the action of PF11 to protect against binge ethanol neurotoxicity.

关键词： pseudoginsenoside-F11 ethanol neurodegeneration neuroinflammation

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Curcumin and ginkgolide B inhibit renal cyst development

Curcumin and ginkgolide B inhibit renal cyst development

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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： Bao-Xue YANG Jin-Sheng GAO Hong ZHOU Tian-Luo LEI Department of Pharmacology School of Basic Medical SciencesPeking Universityand Key Laboratory of Molecular Cardiovascular SciencesMinistry of EducationBeijing 100191China

AIM To develop candidate drugs for treating autosomal dominant polycystic kidney disease (PKD) from natural compound *** An MDCK cyst model, a murine embryonic kidney cyst model and a PKD mouse model were used to screen positive compounds and to evaluate cyst inhibitory *** viability, proliferation, apoptosis, CFTR function and expression,and signaling pathways in MDCK cells were determined to explore the mechanism of cyst *** Curcumin and ginkgolide B were found to significantly inhibit MDCK cyst development in both MDCK cyst model and embryonic kidney cyst model with dose-response *** two compounds neither induced cytotoxicity nor apoptosis in MDCK *** failed to affect the chloride transporter CFTR expression and ***, curcumin and ginkgolide B inhibited forskolin-promoted cell proliferation and promoted the tubule formation in MDCK cells, which indicates they promotes MDCK cell ***,curcumin and ginkgolide B altered Ras/MAPK signaling *** B significantly inhibited cyst enlargement in PKD mouse *** Both cureumin and ginkgolide B inhibit renal cyst formation and enlargement, suggesting that these natural compounds or their analogues might be developed into novel candidate drugs for polycystic kidney disease.

关键词： curcumin ginkgolide B natural product ADPKD renal cyst

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Selective immunosuppression by natural products

Selective immunosuppression by natural products

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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： Qiang XU (State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University, Nanjing 210093,China) State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210093China

Most of current immunosuppressive agents have severe side effects due to their non-selective effect *** we report a series of natural products that show a selective inhibition on T cell-mediated immune response distinct from current drugs. These small molecule compounds include a new cerebroside fusaruside,a plant cyclopeptide astin C,plant flavonoids Jaceosidin,cirsilineol and astilbin,and the fungal metabolites fumigaclavine C and its derivatives,*** them,astin C induces apoptosis of activated T cells with a mitochondria-dependent but not endoplasmic reticulum stress-mediated *** and cirsilineol exert their immunosuppressive effects through downregulation of the IFN-γ/STAT1/T-bet signaling in T *** to fusaruside,this unique compound triggered tyrosine phosphorylation of Src homology 2-containing protein tyrosine phosphatase 2（SHP-2 ） in T cells from C57BL/6 *** the interaction of pY-SHP-2 with cytosolic STAT1 stopped the recruitment of STAT1 to IFN-γreceptor for phosphorylation and selectively inhibited STAT1 signaling,which led to a reduction in Th1 cytokine levels and an improvement of experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid（TNBS） in *** the pY-SHP-2-STATl interaction,by using either the SHP-2 inhibitor NSC-87877 or shp-2 T cells,prevented the inhibition of STAT1 activation and abolished the improvement of colitis by *** above compounds are valuable to be further investigated on the detailed mechanisms arid the possibility as a novel drug candidate for a variety of immune diseases.

关键词： Selective immunosuppression by natural products

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Investigation on the anti-inflammatory effect of Aconitum brachypodum Diels

Investigation on the anti-inflammatory effect of Aconitum br...

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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： Wei REN Da-Jiang ZHOU Jun LI Xian-Ju HUANG College of Pharmacy South Central University for NationalitiesWuhan 430074China

AIM In order to study the anti-inflammatory effects and its mechanism of extract from Aconitum brachypodum Diels (EABD).The present study was conducted to observe the effects of the EABD on the prohferation, apoptosis, production of the nitric oxide (NO) and reactive oxygen species (ROS) of mouse peritoneal macrophages induced by lipopolysaccharide (LPS) in *** The mouse peritoneal macrophages was prepared under sterile condition, then the cells were divided into control group,LPS groups and EABD *** different time of incubation, the cell activities of mouse peritoneal macrophages were analyzed by the methods of *** 33258 fluorescent staining was used to detect the effect of EABD on cell apoptosis induced by *** release in the medium were determined by Griess reagent, and ROS production was determined by fluorescence probe *** EABD could dose-dependently inhibit the activity and apoptosis of mouse peritoneal macrophages induced by LPS,demonstrating a significant anti-inflammatory effect in *** concentrations of EABD could inhibit the production of NO induced by 10 rag· L-1 of LPS in a dose-dependent ***, the production of ROS in mouse peritoneal macrophages induced by LPS was significantly inhibited by *** The extract from Aconitum brachypodum Diels has significant antiinflammatory effect in vitro, which may due to an anti-oxidative mechanism of the folk plant.

关键词： Aconitum brachypodum Diels anti-inflammatory apoptosis nitric oxide reactive oxygen species

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S-propargyl-cysteine-induced angiogenesis was mediated through a H2S/VEGFR2/STAT3 axis

S-propargyl-cysteine-induced angiogenesis was mediated throu...

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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： Jun-Tao KAN~(1,2),Wei GUO~1,Cheng-Rong HUANG~1,Yi-Zhun ZHU~(1,2) (1.School of Pharmacy,Fudan University,Shanghai 201203,China 2.Institutes of Biomedical Sciences, Fudan University,Shanghai 201203,China)

AIM We investigated the pro-angiogenic effect of S-propargyl-cysteine（SPRC）,a novel water-soluble modulator of endogenous hydrogen sulfide,to provide experimental basis for angiogenesis-mediated drug therapy of ischemic heart *** Some models such as Transwell and Matrigel plug were carried out to determine the pro-angiogenic effect of SPRC under normal ***-limb ischemia model was induced to explore the angiogenesis in ischemic condition by laser doppler imaging and angiography. Western blot and immunofluorescence were used to detect the level and location of *** and CHIP were performed to determine the activation of STAT3 and its downstream *** SPRC promoted cell proliferation,adhesion,migration and tube formation of primary HUVEC and increased angiogenesis ex vivo and in vivo under both normal and ischemic conditions. The former research reported HS could directly active VEGFR2 by disrupting the disulfide bonds within ***,we found the interaction between VEGFR2 and STAT3 was also enhanced after ***,the elevated phosphorylation of STAT3 induced by SPRC could be abolished by addition of SU5416,an inhibitor of *** addition,SPRC induced translocation of STAT3 to nucleus,followed by transcriptional activation of downstream *** critical roles of STAT3 in SPRC-induced angiogenesis were confirmed by RNA *** SPRC promoted angiogenesis under both normal and ischemic conditions,and effected through a HS/VEGFR2/STAT3 axis.

关键词： angiogenesis hydrogen sulfide S-propargyl-cysteine STAT3

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Multitarget strategy of traditional Chinese medicine to treat Alzheimer's disease

Multitarget strategy of traditional Chinese medicine to trea...

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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： Lin LI,Lan ZHANG,Ru-Yi ZHANG (Department of Pharmacology,Xuan-wu Hospital of Capital Medical University,Key Laboratory for Neurodegenerative Diseases of Ministry of Education,Beijing 100053,China)

AIM To investigate the effects of Shen-wu capsule(SW) and 2,3,5,4'-tetrahydroxystilbene glucoside(TSG) on multiple targets of *** The drugs were intragastrically administered to the animal models for 1 or 2 *** water maze test was used to detect learning/memory ability,Western blotting and immuno-histochemistry to determine related proteins. RESULTS(1) In APP transgenic mice,SW and TSG improved learning/memory ability,and decreased Aβcontent andβ-secretase expression;(2) in a brain injection model,SW and TSG inhibited microglial activation,and decreased IL-1 and TNF content;(3) in ibotanic acid-induced basal forebrain colinergic damage rat model,SW and TSG improved learning/memory ability,increased the ratio of cholinacetyl-transfetase(ChAT) / cholinesterase(AChE),and enhanced M-receptor density;(4) in dementia rat model induced by mitochondria complexⅣinhibitor sodium azide,SW and TSG improved learning/memory ability,decreased Aβand hyperphosphorylated tau protein,and increased expression of protein phosphortase 2A(PP2A),brain derived neurotrophic factor(BDNF) and ChAT;(5) in aged rats,SW and TSG improved learning/memory ability,decreased cholinergic cell death,and increased expression of nerve growth factor and its receptor trkA in hippocumpus;(6) in aged mice,TSG protected synaptic structure and functions,and inhibited the overexpression and aggregation of alpha-synuclein in hippocampus,striatum and *** SW and TSG can act on multiple targets in the complicated pathogeneses of AD,thus may have strong potential to the treatment of AD.

关键词： traditional Chinese medicine tetrahydroxystilbene glucoside Alzheimer's disease animal model therapeutics

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Pharmacokinetic study of salvianolic acid A after oral administration in SD rats by a liquid chromatography-massspectrometry method

Pharmacokinetic study of salvianolic acid A after oral admin...

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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-Lin SUN,Li ZHANG,Guan-Hua DU (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)

AIM To develop a specific liquid chromatography-mass spectrometry（LC-MS） method for quantification of salvianolic acid A（Sal A）,and study the pharmacokinetics of Sal A after oral administrationin SD *** SD rats were oral administered Sal A 5,10 and 20 mg·kg *** plasma drug concentration was detected by a rapid and sensitive LC-MS *** pharmacokinetic parameters were calculated from plasma concentration-time data using the DAS pharmacokinetic soltware Data Analysis System Version 3.0 *** The calibration curve for Sal A was linear over a range of 2.5 - 1000μg·L with coefficients of correlation>*** intra- and inter-day precisions（CV） of analysis were<10%,and accuracy ranged from 95%to 110%.Stability results showed that Sal A was stable under a variety of storage and analysis *** *** of Sal A 5,10 and 20 mg·kg,the c values for Sal A were estimated to be 31.53,57.39 and 111.91μg·L,respectively. The AUC increased with increasing doses,and the AUC values were 105.93,167.18 and 317.11(μg·L·h),respectively. CONCLUSION This LC-MS method israpid,sensitive and specific for the pharmacokinetic study of Sal *** pharmacokinetic parameters of c and AUC have good linearity with the doses,suggesting linear pharmacokinetics.

关键词： savianolic acid A LC-MS pharmacokinetics

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Acute toxicity of YSY-01A in zebrafish is evaluated by still water method and ip method

Acute toxicity of YSY-01A in zebrafish is evaluated by still...

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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： Bing-Jie XUE,Wei GUO,Kan TONG,Mei ZHANG,Jing-Rong CUI (State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University, Beijing 100091,China)

AIM YSY-01A,a synthetic derivative of the Bortezomib,shows distictive anticancer action,while there is no any reports about its acute *** order to evaluate the acute toxicity of YSY-OIA using the least volume of YSY-OIA,the zebrafish model through two delivery mode in vivo were *** addition,we check the LD of YSY-OIA by zebrafish against by mice. METHODS The zebrafish acute toxicity testing was taken to evaluate the LD of YSY-OIA treated 96 h by both ip and still water method.0.1 ml YSY-01A solution of 9,12.9,18.5,26.4,37.7 and 53.9 mg·kg were delivered by ip injection respectively, 25 ml YSY-01A solution of 16.8,24,34.3,49,70 and 100 mg·L were delivered by still water *** mice acute toxicity testing was taken according to the classical acute toxicity method for *** The zebrafish acute toxicity testing suggested that after YSY-01A treated for 96 h,the LD by ip was 21.26 mg·kg,while the LD by still water method was 32.594 mg·L, sorted as acute toxicity levelⅢ.The LD by mice was 22.35 mg·kg,which was similar to the value of LD by *** Both still water method and ip could measure the LD in zebrafish acute toxicity testing,ip method need less drug and very close to the result of acute toxicity of mice.

关键词： YSY-01A acute toxicity testing zebrafish

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Protective effects of Panax notoginseng saponin on hydrogen peroxide induced toxicity in brain cells

Protective effects of Panax notoginseng saponin on hydrogen ...

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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： Gina N ALESI Richard F KEEP Department of Neurosurgery Medical SchoolUniversity of Michigan Department of Pharmacology Yunnan University of TCM

AIM Oxidative stress resulting from accumulation of reactive oxygen species（ROS） is involved in cell death associated with neurological disorders such as stroke,traumatic brain injury and brain *** compound,that to improve endogenous antioxidant defenses has been proposed for neural *** purpose of the present study was to investigate the potential protective effects of total saponin in leaves of Panax notoginseng（LPNS）,on HO-induced oxidative stress and cell death in brain cell damage in *** LPNS was used to analyzed for its anti-oxidation effects on HO-induced cytotoxicity by LDH assay and HO- induced ROS formation,the expression of inducible nitric oxide synthetase（iNOS）,nuclear factor erythroid 2-related factor 2（Nrf2） and its downstream reactive gene heme oxygenase-1（HO-1 ） were detected by Western blot in primary rat *** oxygen and glucose deprivation（OGD）-indueed cytotoxicity and HO induced morphological modifications in sh-sy5y,a neuronal cell line,were also *** In primary rat cortical astrocyte cells,LPNS dose-dependent reduction of the cell death by lactate dehydrogenase *** protection was found in sh-sy5y cell damage caused by transient exposure to *** protective effects of LPNS on astrocyte were associated with Nrf2 nuclear translocation and upregulated expression of antioxidative systems regulated by Nrf2 such as HO-1,attenuation of the ROS accumulation and inhibited the expression of *** These results demonstrate for the first time that LPNS has antioxidative stress which may has protective effects on neurological disorders.

关键词： oxidative stress total saponin,Panax notoginseng astrocyte sh-sy5y cells

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Effect of long-term alcohol consumption or high glucose and high fat diet on hypertension and kidney and liver function in rats

Effect of long-term alcohol consumption or high glucose and ...

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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： Su-Hong CHEN~1,Gui-Yuan Lü~2*,Chao-Qun XIA~1,Jie SU~2,Qi ZHANG~1 (1.Institute of Chinese Materia Medica,WenZhou Medical College,Wenzhou 325035,China 2.Institute of Materia Medica,Zhejiang Chinese Medical University,Hangzhou 310053,China)

AIM Referring to the relation between hypertension and excessive drinking and high fat diet,we established the hypertension model rats by feeding with alcohol and high glucose and fat diet,which is similar to human *** SD rats,half male and half female,were divided into 3 groups according to their *** first group were fed with alcohol and standard diet(the alcohol concentration increased from 5%to 22%).The second group received high glucose and high fat diet and *** third one,used as normal control group,received standard diet and *** whole experiment lasted 30 *** pressure were measured directly by tail arteries in awake *** were collected to detect the levels of serum ALT,AST,GGT,ALP,TP,ALB,UA,*** After drinking for 8 weeks,the blood pressure of SD rats started to rise *** 17 weeks,the SBP was close to 160 *** 6 weeks,the blood pressure of SD rats which fed with high glucose and high fat diet started to rise significantly and the SBP was close to 160 mmHg after 15 *** the drinking group or high glucose and high fat group,biochemical indexes which reflect liver and kidney functions appeared abnormal after 12 *** The blood pressure of SD rats could increase to some extent by long-term alcohol consumption or high glucose and high fat *** the same time,complications,such as liver and kidney injury,were also observed.

关键词： alcohol high glucose and high fat diet hypertension

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