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Combinational therapeutic targets for Alzheimer's disease based on network pharmacology

Combinational therapeutic targets for Alzheimer's disease ba...

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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： Wen-Xia ZHOU~*,Xiao-Rui CHENG,Peng LI,Sheng YANG,Yong-Xiang ZHANG (Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China)

AIM Alzheimer's disease(AD) is a chronic neurodegenerative disorder and it's pathogenesis remains *** present one-drug,one-target paradigm for anti-AD treatment appears to be clinically unsuccessful,and AD arises via multiple pathological or neurotoxic pathways,so the combinational targets composed of several biomolecules based on bio-network may be optimum for the discovery of anti-AD *** study aims to search the combinational targets for AD based on traditional Chinese medicine (TCM) with multi-function,multi-target characteristics using network pharmacology *** The nootropic effects of TCM prescriptions Liu-Wei-Di-huang decoction(LW),Ba-Wei-Di-Huang decoction(BW),Huang-Lian-Jie-Du decoction(HL), Danggui-Shaoyao-San(DSS),Tiaoxin Recipe(TXF),were validated by cognitive behavior test in senescence accelerated mouse prone 8(SAMP8 ),and the combinational therapeutic targets were investigated using cDNA microarray,RT-PCR,bioinformatics and computational biology *** The TCM prescriptions LW,BW,HL,DSS,and TXF significantly improve the cognitive behavior of *** are 39 genes expression in hippocampus(H) and 52 genes expression in cerebral cortex(C) regulated by LW in SAMP8,13 in H and 7 in C by BW,34 in H and 41 in C by HL,7 in Hand 11 in C by DSS,24 in H and 11 in C by TXF. These genes regulated by five prescriptions involve in the biomolecular *** were 384 nodes and 383 edges in the network effected by LW,384 nodes and 343 edges in the network effected by LW,86 nodes and 76 edges by BW,298 nodes and 262 edges by HL,92 nodes and 85 edges by DSS,155 nodes and 146 edges by TXF *** hub nodes included 9 molecules,STUB1, STRN4,RPS6KA1,ROCKl,MAP3K3,TICAM2,MAPT,UBE2D2 and ***,RPS6KA1,SLC17A7 and FHIT are the common nodes effected by every one of five prescriptions and may be therapeutic potential targets for *** The molecules including 9 hub nodes and 3 common nodes might formulate the

关键词： Alzheimer's disease traditional Chinese medicine combinational therapeutic targets molecular network network pharmacology

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Reversal effects and mechanisms of Ganoderma lucidum polysaccharide on multidrug resistance in K562/A in vitro and in vivo

Reversal effects and mechanisms of Ganoderma lucidum polysac...

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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-Dong LI,Nan SHEN,Min LI,Zhi-Bin LIN (Department of Pharmacology,School of Basic Medical Sciences,Peking University Health Science Center, Beijing 100191,China)

AIM To observe the reversal effects of Ganoderma lucidum polysaccharide（Gl-PS） on multidrug resistance（MDR） to K562/A in vitro and in *** investigate the mechanism of MDR-reversal effect on *** In vitro,K562/A cells were cultured for 2 weeks in ADM-free medium prior to the *** resistance index of the K562/A cells toward ADM was detected by CCK-8 *** reversal effect of GZ-PS(50,100 and 200 mg·L ) on the multidtug K562/A cell toward ADM was detected by CCK-8 *** protein expression of GST-πwas determined by Western blot,and the early apoptosis effect of GZ-PS onK562/A was detected by Annexin V *** vivo,K562/A cells in the logarithmic growth phase were subcutaneously injected in the right flank of nude mice,and the parent K562 cells were subcutaneously injected in the left flank of the nude *** injection contained 1×10～7 *** nude mice were divided into seven groups:saline control group,verapamil combined with ADM group, ADM group,Gl-PS(100 mg·kg) group,G/-PS(50,100 and 200 mg·kg) combined with ADM group,*** GST-πmRNA expression was determined by reverse-transcriptase polymerase chain reaction（RT-PCR）.The expression of GST-πand caspase 3 was assayed by Western *** IC of K562/A and K562 to ADM were 38.33 and 0.78 mg·L,respectively. GZ-PS(50,100 and 200 mg·L) could decrease the IC of K562/A to ADM,IC of K562/A to ADM were 28.05,24.21 and 23.61 mg·L,***-PS(100 and 200 mg·L ) could effectively reverse MDR-resistance（P<0.05）.GZ-PS(50,100 and 200 mg·L ) could not effectively decrease the IC of K562 to ***-PS(100 and 200 mg·L ) could decrease the protein expression of GST-πin vitro（P<0.05）,while Gl-PS could not significantly change the protein level of GST-π.Gl-PS(100 and 200 mg·L ) could significantly induce the early apoptosis of K562/A in vitro（P<0.05 ）.After administration of Gl-PS(50,100 and 200 mg·kg ) combined with ADM for 14 d,the groups of middle and high dose could significa

关键词： Ganoderma lucidum polysaccharide multidrug resistance glutathione S-transferaseπ K562/A

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Inhibition of cell cycle progression via p27Kip1 upregulation and the PDK-Akt/PKB survival pathway by Rhus verniciflua Stokes

Inhibition of cell cycle progression via p27Kip1 upregulatio...

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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： Seong-Gyu KO Department of Basic Science of Koreanl Medicine Lab of Clinical Biology and Pharmaco genomicsCenter for Clinical Research and GenomicsCollege of Korean MedicineKyung Hee UniversityDongdaemun-guSeoulRepublic of Korea

ABM Botanical preparations are widely used by patient with cancer in Korea,Japan and *** verniciflua Stokes（RVS） has traditionally been used as a medicinal ingredient for the therapy of stomach and uterine *** The AGS human gastric cancer cell line and normal rat intestinal epithelial（RIE1） cell lines were used and grown in RPMI 1640 or DMEM supplemented with 10%（V/V） heat-inactivated fetal bovine serum and 1%penicillin-streptomycin in a 37℃humidified incubator with 5%*** viability assay,Western blot and cytochrom c release analysis were *** measure△ψ,1×10～6 cells treated with an ethanol extract of RVS for various amounts of time were stained with 5 mg·L JC-1（molecular probes,5,5',6,6'tetrachloro -1,1',3,3' -tetraethylbenzimidazol-carbocyanine iodide）.For transient transfection,cells were seeded at a density of 1×10～5 cells per 60 mm dish in 1.5 ml of RPMI 1640 *** were then transfected with 2μg of ***.K179M using LipofectAMINE *** transfection was done as suggested by Qiagen with slight *** brief,AGS cells were plated at 1×10～5 per 60 mm *** next day,cells were transfected with 50 nmol·L of siRNA-control and siRNA-Akt/PKB using Lipofe ctAMINE *** transfection for 6 h,normal medium（RPMI 1640 medium containing 10%FBS） was added and cells were further incubatedfor 12 h prior to treatment with an ethanol extract of *** The extract induces G-cell cycle arrest through the regulation of cyclins,the induction of p27Kip1,and decrease the CDK2 kinase *** upregulated p27Kip1 level is caused by protein stability increment by the reduction of Skp2,a key molecule related with p27Kip1 ubiquitination and degradation,and de novo protein *** extract induces apoptosis through the expression of Bax,poly（ADP-ribose） polymerase（PARP） and activation of caspase 9 and caspase *** was mediated by the loss of mitochondrial membrane potential[MMP,Deltapsi（m）]and the release of cytochrome

关键词： Akt/PKB p27 skp2 apoptosis Rhus verniciflua Stokes

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Heijiangdan Ointment on relieving oxidative stress during radiation dermatitis induced by 60Coγ-ray in mice

Heijiangdan Ointment on relieving oxidative stress during ra...

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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： Yang LIN~1,Ming-Wei YU~1,Xiao-Min WANG~(1*),Guo-Wang YANG~1,Qi FU~1,Yong-Mei XU~1, Xiao-Qin LOU~1,Rui-Yun PENG~2,Ya-Bing GAO~2,Li ZHAO~2,Li-Feng WANG~2 (1.Department of Oncology,Beijing Hospital of TCM Affiliated to Capital Medical University,Beijing 100010, China 2.Institute of Radiation Medicine,Academy of Military Medical Sciences,Beijing 100850,China)

AIM To investigate the effects of Heijiangdan Ointment on regulating oxidative stress in Coγ-ray radiation injured dermatitis tissue in *** Female Wistar mice with 4 grade radiation dermatitis induced by Coγ-ray were randomly divided into 4 groups（n = 12）,the Heijiangdan Ointment group,the recombinant human epidermal growth factor（rhEGF） group,the Trolox group and the model group,and the negative control group was set up *** 11 and 21 day,6 mice in each group were *** levels of superoxide dismutase（SOD）,malondialdehyde（MDA） and lactate dehydrogenase（LDH） were detected by using *** fibroblast mitochondria were observed by transmission electron *** SOD activity was（10.4±1.0）kU·g protein,MDA level was（15.7±0.6）μmol·g protein and LDH activity was（2184±87 ） U·g protein, indicated that on 11 day damage induced by oxidative stress was *** activity increased to（15.1±1.0）kU·g protein, MDA levels decreased to（12.1±0.6）μmol·g protein and LDH activity decreased to（1920±46） U·g protein in Heijiangdan Ointment *** was a significant difference between Heijiangdan Ointment group and the control group（P<0.05 ）.SOD activity was（15.8±0.2） kU·g protein,MDA level was（9.5±0.3）μmol·g protein and LDH activity was（1784±50） U·g protein,suggesting that on 21 the damage of oxidative stress was *** Heijiangdan Ointment group,SOD activity increased to （19.4±0.6） kU·g protein,MDA levels decreased to（7.4±0.3）μmol·g protein and LDH activity decreased to（1549±62）U·g *** was a significant difference between Heijiangdan Ointment group and the control group（P<0.05）.Under transmission electron microscopic observation,fibroblast mitochondria was swelling and cristae was fractured in the model *** in Heijiangdan Ointment group,the swelling of mitochondria was limited and rough endoplasmic reticulum was more relaxed. CONCLUSION Heijiangdan Ointment can relieve the injury of oxidative stress,increase the

关键词： Heijiangdan Ointment radiation dermatitis oxidative stress antioxidant fibroblast mitochondria transmission electron microscope

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SCM-198 attenuates lipopolysaccharide-induced inflammation in microglia and improves cognitive impairment caused by β-amyloid protein fragment 1-40 in rats

SCM-198 attenuates lipopolysaccharide-induced inflammation i...

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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： Zhen-Yi HONG Xue-Ru SHI Kai ZHU Ting-Ting WU Yi-Zhun ZHU Department of Pharmacology School of PharmacyFudan UniversityShanghai 201203China

AIM Chronic inflammation in central nervous system (CNS) is a conspicuous hallmark in neurodegenerative diseases, including Alzheimer's disease (AD) and microglia activation is now widely accepted as a key factor in neuroinflammatory ***, also called SCM-198, is an alkaloid extracted from Herba *** the present study, we investigated its possible anti-inflammatory therapeutic effects both in vitro and in *** Immortalized murine BV-2 microglial cell line and purified rat primary microglia were incubated with lipopotysaccharide (LPS) 1 mg-L-1 or were preincubated with different concentrations (0.01-10 μmol ·L-1) of SCM198 2 h before LPS was *** viability, nitric oxide production, proinflammatory cytokine release were measured by MTT assay, Griess reaction and ELISA, ***-time PCR and Western blot were used to analyze gene and protein expressions and immunocytochemistry staining were performed for NF-κB translocation in ***, microglia/neuron co-culture system was used to determine whether SCM-198 could protect neuron indirectly via inhibition the activation of *** in vivo study, bilateral intrahippocampal β-amyloid protein fragment 1-40 (Aβ1-4o) injections were selected as model:60 male Sprague-Dawley rats were randomly divided into six groups: sham group, Aβ1-4o group, Aβ1-40 + SCM198 15, 30 and 60 rag· kg-1 groups, Donepezil group (DON, 1.0 rag-kg-1 as a positive control) (n =10, respectively).Cognitive performance was evaluated by novel object recognition task (NOR) and Morris water maze (MWM), microglia activation was detected by immunohistochemistry; gene and protein expressions were analyzed by real-time PCR, ELISA, Western *** SCM-198 could reduce nitric oxide production from LPS-activated microglia and could inhibit iNOS, TNF-α, IL-11β mRNA and protein expressions both in vitro and in ***, LPS-induced NF-κB translocation in BV-2 cells was effectively

关键词： Alzheimer' s disease SCM-198 microglia lipopolysaccharide

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Effects of Morinda Offwinalis capsule on bone mineral density, bone metabolism ,bone mineral contents and biomechanical and morphological properties in ovariectomized rats

Effects of Morinda Offwinalis capsule on bone mineral densit...

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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： Ye LI Wei-Hai CHEN Cong-Cong ZHANG Xiao-Na ZHANG Min HOU Qing TANG Xiao-Yu XU Department of Pharmaceutical Sciences Chongqing Research Center for Efficacy Evaluation & Engineering TechnologyInstitute of Traditional Chinese MedicineSouthwest UniversityChongqing 400716China Department of PsychologySouthwest UniversityChongqing 400716China

AIM To find out the effects of Morinda Offwinalis capsule on the bone mineral density and metabolism in ovariectomized *** Rats were ovariectomized and an osteoporotic animal model was built, by which the organ indexes, the difference of the bone mineral density, bone minerals, tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (AKP),osteocalcin (OC), calcium (Ca), phosphorus (P), 1,25-dihydroxyvitaminD3 (1,25 (OH) 2VD3), parathyroid hormone (PTH) and osteogenic growth peptide (OGP) concentration in the blood, as well as pyridinium (PYD) concentration in the urine before and after administration was to be found out, bone's physical, biomechanical and morphological indexes were measured and the relevant parameters were calculated so as to observe the effects of the *** Compared with model Group, the 3-month administration of Morinda Officinalis capsule via oral garage led to a significant increase (P < 0.05) in serm OC, Ca and Zn content, vertebral maximum load, a highly significant increase (P < 0.01) in vertebral bone mineral density (BMD) , serm OGP , Percentage of Tibial Cortical Bone Area (% ***) and decrease (P <0.01) in urine PYD, serm AKP and TRAP, percentage of bone marrow cavity area (% ***) and a significant increase(P <0.05) in were observed at high, medium and low doses of Morinda Officinalis capsule,which were 810,270 and 90 mg·kg-1 respectively; a highly significant increase in serum 1,25 (OH) 2 VD3 (P < 0.01) and a significant increase (P < 0.05) in femoral ash weight, femoral maximum load and modulus, percentage of vertebral trabecular bone area (%***) were observed at high and medium doses of Morinda Offtcinalis capsule, which were 810 and 270 mg·kg-1, respectively; a significant increase in the femoral mineral density and vertebral modulus (P < 0.01) as well as in the iron, copper, calcium and magnesium concentrations , the displacement of femur and vertebra, area of cort

关键词： Morinda Officinalis capsule osteoporosis bone metabolism bone mineral density and content biomechanics and morphology

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Combinational therapeutic targets for Alzheimer's disease based on network pharmacology

Combinational therapeutic targets for Alzheimer's disease ba...

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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： Wen-Xia ZHOU Xiao-Rui CHENG Peng LI Sheng YANG Yong-Xiang ZHANG Beijing Institute of Pharmacology and Toxicology Beijing 100850China

AIM Alzheimer's disease (AD) is a chronic neurodegenerative disorder and it's pathogenesis remains *** present one-drug, one-target paradigm for anti-AD treatment appears to be clinically unsuccessful, and AD arises via multiple pathological or neurotoxic pathways, so the combinational targets composed of several biomolecules based on bio-network may be optimum for the discovery of anti-AD *** study aims to search the combinational targets for AD based on traditional Chinese medicine (TCM) with muhi-function, multi-target characteristics using network pharmacology *** The nootropic effects of TCM prescriptions Liu-Wei-Di-huang decoction (LW), Ba-Wei-Di-Huang decoction (BW), Huang-Lian-Jie-Du decoction (HL),Danggui-Shaoyao-San (DSS), Tiaoxin Recipe (TXF), were validated by cognitive behavior test in senescence accelerated mouse prone 8 (SAMP8), and the combinational therapeutic targets were investigated using cDNA microarray, RT-PCR, bioinformatics and computational biology *** The TCM prescriptions LW, BW, HL, DSS, and TXF significantly improve the cognitive behavior of *** are 39 genes expression in hippocampus (H) and 52 genes expression in cerebral cortex (C) regulated by LW in SAMP8, 13 in H and 7 in C by BW, 34 in H and 41 in C by HL, 7 in H and 11 in C by DSS, 24 in H and 11 in C by *** genes regulated by five prescriptions involve in the biomolecular *** were 384 nodes and 383 edges in the network effected by LW, 384 nodes and 343 edges in the network effected by LW, 86 nodes and 76 edges by BW, 298 nodes and 262 edges by HL, 92 nodes and 85 edges by DSS, 155 nodes and 146 edges by TXF *** hub nodes included 9 molecules, STUB1,STRN4, RPS6KA1, ROCK1, MAP3K3, TICAM2, MAPT, UBE2D2 and ***, RPS6KA1, SLC17A7 and FHIT are the common nodes effected by every one of five prescriptions and may be therapeutic potential targets for *** The molecules including 9 hu

关键词： Alzheimer' s disease traditional Chinese medicine combinational therapeutic targets molecular network network pharmacology

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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 Jian-Xun LIU Wei DONG Peng LI Lei LI Beijing University of Chinese Medicine Beijing 100029China The Experimental Research CenterXiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China Beijing University of Chinese MedicineBeijing 100029China The Experimental Research Center Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China

AIM To investigate the effect of citric acid and L-malate, two main components of Fructus Chwerospondiatis, 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-1) in 3 consecutive days, *** lh after the last administration, rats were subjected to 40 min ischemia by occluding the left anterior descending coronary artery and 120 rain *** infarct size, serum levels of tumor necrosis factor-or (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-1) and dihizem(45 rag·L-1), 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-1) 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-1) treatment significandy 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 (400and 200 mg· L-1) significantly reduced the rate of apoptosis in cells (P < 0.05 or P < 0.01).CONCLUSION Our results demonstrate citric acid and L-ma

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

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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 sign...

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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 En-Yi HUANG Ke YANG Gui-Yuan L(U) Tong-Chuan HE Zhejiang Chinese Medical University Hangzhou 310053China Molecular Oncology LaboratoryDepartment of SurgeryUniversity of Chicago Medical CenterChicagoIL 60637USA

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 MTI 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 Modal 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 boating HCT116 cells as *** with PPD (30 mg·kg-1) for 1-3 weeks could reduce the tumor size of nude mice implanted with the HCT116 *** also changed the expression of AKAPAL8 and *** assay indicated PPD significantly suppressed the signals of NFκB, JNK and MAPK/ERK signaling *** These results suggest that AKAPAL8 and PITPNA m

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

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C-Jun N-terminal kinase/stress-activated protein kinase is critical for growth factors-induced angiogenesis in vitro and in vivo

C-Jun N-terminal kinase/stress-activated protein kinase is c...

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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： Li-Li JI Kai-Kai SHEN Bin LU Zheng-Tao WANG Shanghai R&D Centre for Standardization of Chinese Medicines Shanghai 201210China The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201210China The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201210China

AIM The present study was designed to obverse whether c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) regulates the angiogenesis of human umbilical vein endothelial cells (HUVEC) induced by angiogenic growth *** Cell proliferation, migration and tube formation were observed in HUVEC, and in vivo Matrigel plug assay was ***-blotting analysis was used to observe the related *** Vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) both stimulated HUVEC proliferation, migration and tube formation in a concentration-dependent *** results showed that VEGF and bFGF induced the activation of JNK/SAPK, p38 kinase and extracellular signal-regulated kinase 1 and 2 (ERK1/2), while JNK/SAPK inhibitor SP600125 and specific siRNA both blocked all those angiogenic effects induced by VEGF or ***, in vivo matrigel plug assay showed that SP600125 inhibited VEGF-induced ***,JNK/SAPK inhibitor SP600125 and specific siRNA inhibited VEGF or bFGF-induced JNK/SAPK signal cascade *** results showed that SP600125 and JNK/SAPK siRNA decreased VEGF-induced VEGFR2 (Flk-1/KDR) sustained phosphorylation in *** Taken together, all these results indicates that JNK/SAPK signal pathway plays an important role in mediating growth factors-induced angiogenic responses, and thus JNK/SAPK is a potential target for drug development in angiogenesisrelated diseases such as cancer, diabetic retinopathy, etc.

关键词： c-Jun N-terminal kinase/stress-activated protein kinase vascular endothelial growth factor basic fibroblastic growth factor human umbilical vein endothelial cells angiogenesis

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