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Anticancer activity of sodium caffeate and its mechanism

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Acta Pharmacologica Sinica 2005年第10期26卷 1248-1252页

作者： Feng XU~(2,3.4), Sheng-hua ZHANG~3. Rong-guang SHAO~3. Yong-su ZHEN~3.~2 Department of Pharmacology Zhujiang Hospital, Southern medical university Guangzhou 510280 ~3.Department of Ontology Medicinal Biotechnology, Chinese Academy of medical Sciences and Peking Union medical College, Beijing 100050, china Department of Pharmacology Zhujiang Hospital Southern Medical University Guangzhou China Department of Oncology Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Aim: To study the anticancer activity of sodium caffeate （SC）. Methods: A nucleoside transport assay was used to analyze the inhibitory effects of SC on nucleoside rescue. The MTT assay was used to measure cell proliferation. Flow cytometrywas used to measure the apoptosis of BEC-7402 induced by SC and the cell cycledistribution change. Western blotting analysis was employed to investigate Bcl2, caspase and Bax expression. Intracellular Ca2+and mitochondrial membranepotential were determined by flow cytometry. In vivo anti-tumor activity wasmeasured using a tumor transplantation model in mice. Results: SC inhibited thenucleoside transport of BEL-7402 cells with an IC50of 1.02 mg/mL. SC inhibitedtumor cell proliferation with an IC50between 100 μg/mL and 200μg/mL. SC induced BEL-7402 cell apoptosis in a time-and dose-dependent manner, which wasinduced by arresting cells in S phase. The in vivo study showed that tumorgrowth was inhibited in a dose-dependent manner. Activated caspase-3.and Baxexpression were up-regulated after treatment with SC, while Bcl-2 expression wasdown-regulated. Intracellular Ca2+was increased while mitochondrial membranepotential was decreased by SC. Conclusion: SC is a new anticancer agent withpromising potential.

关键词： caffeic acid anticancer activity cell division cell apoptosis cell cycle phytogenic antineoplastic agent flow cytometry Western blotting

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats

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World Journal of Gastroenterology 2001年第5期7卷 672-677页

作者： Li-Hong Zhang~1 Chang-Bai Yao~2 He-Quan Li~3.1 Department of Anesthesiology,Second Clinical College,china medical university,Shenyang 110003.Liaoning Province,china2 Department of General Surgery,Second Clinical College,china medical university3.Department of Pathophysiology,china medical university Department of Anesthesiology Second Clinical College China Medical University Liaoning Province China. cumzhanglihong@***

AIM: To compare the effects of extract F of red-rooted Salvia (EFRRS) on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock and reperfusion in rats. METHODS: The rats were subject to hemorrhagic shock and followed by reperfusion, and were divided randomly into two groups. Group 1 received saline, and group 2 received EFRRS intravenously. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesional area in the corpus or antrum. The degree of gastric mucosal lesions (DGML) was catalogued grade 0,1,2 and 3. The concentrations of prostaglandins (PGs) were measured by radioimmunoassay. The concentration of MDA was measured according to the procedures of Asakawa. The activity of SOD was measured by the biochemical way. The growth rates or inhibitory rates of above-mentioned parameters were calculated. RESULTS: As compared with IGML (%), grade 3.damage (%) and MDA content (nmol/g tissue) of gastric antrum which were respectively 7.96 +/- 0.59, 3..86 +/- 4.96 and 156.98 +/- 16.12, those of gastric corpus which were respectively 23.18 +/- 6.82, 58.44 +/- 9.07 and 23..56 +/- 19.3. increased markedly (P 3.01 +/- 1.01, 8.3. +/- 1.95, 540.48 +/- 182.78, 714.3. +/- 123.74, 17.3. +/- 5.93.and 13..29 +/- 13.3. were markedly lower than those of antrum which were respectively 13.92 +/- 2.25, 26.78 +/- 6.06, 2218.56 +/- 43..12, 253..76 +/- 492.3., 43.46 +/- 8.51 and 187.45 +/- 17.67 (P3..56, 3.8.62, 40.75, 74.75, 92.29 and 122.25 were higher than those in antrum which were respe

关键词： Phytotherapy Salvia Alprostadil derivatives Animals Dinoprostone Gastric Mucosa Hydroxyl Radical Male Malondialdehyde Plant Extracts Pyloric Antrum Rats Rats, Wistar Reperfusion Injury Research Support, Non-U.S. Gov't Shock, Hemorrhagic Superoxide Dismutase Thromboxane B2

Role of melatonin in Alzheimer-like neurodegeneration

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Acta Pharmacologica Sinica 2006年第1期27卷 41-49页

作者： Jian-zhi WANG~(2,4) Ze-fen WANG~(2,3.2 Pathophysiology Department,Key Laboratory of Neurological Diseases of Hubei Province,Tongji medical School,Huazhong university of Science and Technology,Wuhan 43.03.,china 3.Department of Physiology,medical College,Wuhan university Wuhan 43.071,china Pathophysiology Department Key Laboratory of Neurological Diseases of Hubei Province Tongji Medical School Huazhong University of Science and Technology Wuhan China Department of Physiology Medical College Wuhan University Wuhan China

Alzheimer disease (AD),an age-related neurodegenerative disorder with progres-sive loss of memory and deterioration of comprehensive cognition,is character-ized by extracellular senile plaques of aggregated β-amyloid (Aβ),and intracellularneurofibrillary tangles that contain hyperphosphorylated tau *** showed that melatonin,an indoleamine secreted by the pineal gland,mayplay an important role in aging and AD as an antioxidant and *** decreases during aging and patients with AD have a more profoundreduction in this *** from clinical trials indicate that melatonin supple-mentation improves sleep,ameliorates sundowning,and slows down the progres-sion of cognitive impairment in Alzheimer's *** efficiently pro-tects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloidproperties:it not only inhibits Aβ generation,but also arrests the formation ofamyloid fibrils by a structure-dependent interaction with Aβ.Our recent studieshave demonstrated that melatonin efficiently attenuates Alzheimer-like *** the exact mechanism is still not fully understood,a direct regulatory influence of melatonin on the activities of protein kinases andprotein phosphatases is ***,melatonin also plays a role inprotecting cholinergic neurons and in ***,the neuroprotectiveeffects of melatonin and the underlying mechanisms by which it exerts its effectsare *** capacity of melatonin to prevent or ameliorate tau and Aβpathology further enhances its potential in the prevention or treatment of AD.

关键词： Alzheimer disease melatonin tau,beta amyloid

Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotype in healthy Chinese subjects

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Acta Pharmacologica Sinica 2005年第3期26卷 384-388页

作者： Yong-mei HU~(2,3. Jian-ming XU~(3.5) Qiao MEI~3.Xin-hua XU~3.Shu-yun XU~42 Anhui Geriatric Institute 3.Department of Gastroenterology,First Affiliated Hospital of Anhui medical university 4 Clinical Pharmacology Institute,Anhui medical university,Hefei 23.022,china Anhui Geriatric Institute Hefei 230022 China Department of Gastroenterology First Affiliated Hospital of Anhui Medical University Hefei 230022 China Clinical Pharmacology Institute Anhui Medical University Hefei 230022 China

Aim:To investigate whether the pharmacodynamics and pharmacokinetics ofrabeprazole are dependent on CYP2C19 genotype status in healthy Chinese ***:The CYP2C19 genotype status of healthy Chinese Hart volun-teers was determined using the polymerase chain reaction-restriction fragmentlength polymorphism *** healthy subjects volunteered to participatein the *** were seven homozygous extensive metabolizers （homEM）,sixheterozygous extensive metabolizers （hetEM）,and seven poor metabolizers （PM）.All subjects were Helicobactor pylori-negative,which was determined by sero-logy and13.-urea breath *** （20 mg） was taken orally once daily inthe morning for 8 days,and intragastric pH values were monitored for 24 h byDigitrapper pH after day 1 （single dose） and day 8 （repeated dose）.Meanwhile,blood samples were collected at various time-points for 24 h after *** serum concentrations of rabeprazole were measured using high-performanceliquid ***:The mean area under the curve （AUC） values forrabeprazole differed among the three different genotype groups,with a relativeratio of 1.0,1.3.and 1.8 after a single dose and 1.0,1.1,and 1.7 after repeated dosesin the homEM,hetEM,and PM groups,*** AUC values forrabeprazole after a single dose and after repeated doses were significantly differ-ent between the homEM and PM groups,but not between the homEM and hetEMor hetEM and PM *** significant differences in intragastric pH median,pH>4 total time,and pH>4 time percentage of 24 h,were observed among the threedifferent genotype groups after a single dose or after repeated doses of ***:In healthy Chinese Hart subjects,the pharmacokinetics of rabeprazoleare dependent on a certain degree on CYP2C19 genotype status;however,theacid-inhibitory efficacy of rabeprazole is not influenced significantly by CYP2C 19genetic polymorphism.

关键词： polymorphism(genetics) pharmacokinetics pharmacodynamics rabeprazole

Reduced cell death by inosine pretreatment after photochemically induced cerebral ischemia in adult rats

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Progress in Natural Science:Materials International 2008年第12期18卷 1513-1518页

作者： Zhongliang WU~(a,1) Fei Liu~(a,1) Yazhou Wang~a Xiying Jiao~a Ming Shi~a Qingbo Zhao~b Gong Ju~a Siwei You~a a Institute of Neurosciences,The fourth military medical {3.,17 Changlexi Road,Xi’an 71003.,china b Department of Biostatisties,The fourth military medical {3.,17 Changlexi Road,Xi’an 71003.,china Institute of Neurosciences The Fourth Military Medical University 17 Changlexi Road Xi’an 710032 China Department of Biostatistics The Fourth Military Medical University 17 Changlexi Road Xi’an 710032 China

Protective effect of inosine against cell death after photochemically induced focal cerebral ischemia was investigated in adult rats. Intraperitoneal injection of inosine was started 24 h before operation and continued till the animals were *** TUNEL method and Nissl staining were used to identify apoptosis and necrosis,***-positive cells were located in the transitional zone between the necrotic core and normal *** mean maximum area of the necrotic cores and mean number of TUNEL-positive cells 24 h after operation were reduced significantly in the inosine-treated rats when compared with those in the saline-treated control animals. We suggest that inosine can significantly reduce both necrosis and apoptosis following cerebral ischemia induced by photothrombosis in adult rats.

关键词： Cell death Cerebral infarction Inosine Photothrombosis Rat

Down-regulation of C-type natriuretic peptide receptor by vasonatrin peptide in cardiac myocytes and fibroblasts

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Acta Pharmacologica Sinica 2004年第4期25卷 26-32页

作者： Shun-yan Lü, Miao-zhang ZHU2, Dian-shi WANG3. Jun YU, Hai-tao GUO, Yu-zhen HU, Qi-ming WEI4 Department of Physiology, Departmentof Anatomy, fourth military medical {3., Xi-an 71003., china 4Cardiorenal 3. Molecular Laboratory, {3. of Maryland School of Medicine, Baltimore21201, USA Department of Physiology Fourth Military Medical University Xi'an 710032 Cardiorenal Molecular Laboratory University of Maryland School of Medicine Baltimore 21201 美国

AIM: To investigate the regulatory effects of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in cultured neonatal rat cardiac myocytes and fibroblasts. METHODS: Quantitative RT- PCR was undertaken to evaluate the levels of NPR-C mRNA and radioimmunoassay was used to determine the formation of intracellular cGMP. RESULTS: Twenty-four hours hypoxic exposure increased the level of NPR-C mRNA in cardiomyocytes, while did not alter the expression of NPR-C in cardiac fibroblasts. VNP (1×10-8-1×10-6 mol/L) reduced the levels of NPR-C mRNA in cardiac myocytes induced by hypoxia in a concentration-dependent manner, and with high concentration (1×10-6mol/L) also decreased the expression of NPR-C in cardiac fibroblasts and air-control cardiac myocytes. The inhibitory effects of VNP on the expression of NPR-C was mimicked by 8- bromo-cGMP 1×10-6 mol/L (a membrane permeable analog of cGMP). VNP (1×10-8-1×10-6mol/L) increased the formation of intracellular guanosine-3.,5'-cyclic monophosphate (cGMP) in both cardiac myocytes and fibroblasts. HS-142-1, the particulate guanylyl cyclase-coupled receptor antagonist, partially abrogated the above effects of VNP. CONCLUSION: Hypoxic exposure for 24 h up-regulated the expression of NPR-C in cultured neonatal rat cardiac myocytes. VNP decreased the expression of NPR-C in cardiac myocytes and fibroblasts under both air- control and hypoxic condition, which was at least partially mediated by guanylate cyclase linked natriuretic peptide receptors through increasing the intracellular cGMP.

关键词： C-type natriuretic peptide myocardium fibroblasts hypoxia

Treatment with Vector-expressed Small Hairpin RNAs against Ki67 RNA-induced Cell Growth Inhibition and Apoptosis in Human Renal Carcinoma Cells

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Acta Biochimica et Biophysica Sinica 2006年第4期38卷 254-261页

作者： Jun-Nian ZHENG~(1,3.) Ya-Feng SUN~(2#) Dong-Sheng PEI~2 Jun-Jie LIU~1 Teng-Xiang MA~3.Rui-Fa HAN~3.Wang LI~1 Dian-Bao ZHENG~1 Jia-Cun CHEN~1 Xiao-Qing SUN~1 1 Laboratory of Urology,Affiliated Hospital of Xuzhou medical College,Xuzhou 221002,china 2 Research Center for Biochemistry and Molecular Biology,Xuzhou medical College,Xuzhou 221002,china 3.Institute of Urology,medical university of Tianjin,Tianjin 3.0211,china Laboratory of Urology Affiliated Hospital of Xuzhou Medical CollegeXuzhou 221002 China Institute of Urology Medical University of TianjinTianjin 300211 China Research Center for Biochemistry and Molecular Biology Xuzhou Medical CollegeXuzhou 221002 China

Short hairpin RNAs (shRNAs) transcribed *** polymerase Ⅲ promoters can triggersequence-selective gene silencing in mammalian *** virtue of their excellent function in knocking downexpression of cancer-associated genes,shRNAs could be used as new therapeutic agents for *** of Ki67 in renal cancer has been correlated to a more aggressive tumor phenotype,inhibitionof Ki67 protein expression by means of shRNAs seems to be a promising approach for the therapy of *** this study,we constructed an expression plasmid encoding shRNAs against the Ki67 gene,namedpSilencerKi67,and transfected it into human renal carcinoma *** pSilencerKi67 was shown to signifi-cantly knock down the expression of the Ki67 gene in human renal carcinoma cells,resulting in inhibitingproliferation and inducing apoptotic cell death that can be maintained for at least *** findings offer thepromise of using vector-based shRNAs against Ki67 in renal cancer gene therapy.

关键词： Ki67 gene shRNAs renal cell carcinoma proliferation apoptosis

Effect of P145^(INK4b/MTS2) on the proliferation of human hepatoma cells SMMC-7721

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Chinese Science Bulletin 2000年第15期45卷 1408-1412页

作者： ZHANG Hong, LIU Huitu & SHI Fawu1. Key Laboratory of Cell Proliferation and Regulation Biology, Beijing Normal university, Beijing 100875, china 2. Institute of Basic medical Science, General Hospital of People’s Liberation Army LA, Beijing 10003., china 3. Institute of medical Information, medical Academy of china, Beijing 100020, china Correspondence should be addressed to Liu Huitu Key Laboratory of Cetl Proliferation and Regulation Biology Beijing Normal University Beijing China Institute of medical Information Medical Academy of China Beijing China Institute of Basic medical Science General Hospital of People’s Liberation Army LA Beijing China

The full length cDNA coding for P15 INK4b, which is a cyclin-dependent kinase inhibitor, was cloned to plasmid PXJ41-neo (Eco R I IXho 1 site) and the new constructed plasmid pXJp15 was obtained. pXJp15 was transferred into the human hepatoma SMMC-7721 cells by lipofectine reagent. After G418 selection, a series of cell lines stably expressing high levels of P15 (named SHT) and the clone containing vector PXJ41-neo only (named SVXJ) were obtained by Northern and Western analysis. The results showed that the proliferation of SHT cells is inhibited compared with that of SVXJ cells. Cell cycle analysis indicated that overexpressing of P15 inhibited the growth of SHT cells by decreasing progrssion of cells from G1 to S and G2 to M phases. The levels of c-Myc and c-Fos were obviously decreased in SHT cells compared with control cells by Western blotting. The decreased expression of oncogene may be one of the molecular mechanisms of the effect of P15 on the proliferation of in SHT cells.

关键词： CKIP15 human hepatoma cell cycle oncogene.

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Corticosterone activates Erk1/2 mitogen-activated protein kinase in primary hippocampal cells through rapid nongenomic mechanism

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Progress in Natural Science:Materials International 2005年第4期 38-43页

作者： QI Aiqun 1, QIU Jian 1, XIAO Lin 2 and CHEN Yizhang 2,3. *(1. Department of Physiology, Second military medical university, Shanghai 20043.,{3. 2. Department of Neurobiology, Second military medical university, Shanghai 20043.,{3. 3. Institute of Neuroscience, Second military medical university, Shanghai 20043.,{3.) Department of Physiology，Second military medical university，Shanghai 20043.，{3. Department of Neurobiology，Second military medical university，Shanghai 20043.，{3. Department of Neurobiology，Second military medical university，Shanghai 20043.，{3. Institute of Neuroscience，Second military medical university，Shanghai 20043.，{3.

Nongenomic effects of glucocorticoids (GC) in various cell types have been well documented, but it still remains unknown whether the mechanism also works in hippocampus which is a crucial target of glucocorticoids in neural system during physiological and/or pathophysiological processes. We present here that corticosterone (B) could rapidly activate Erk1/2 mitogen activated protein kinase (MAPK) in primarily cultured hippocampal cells within minutes, with a bell shaped time dependent curve which peaked at 15min and then went down to normal level in 3. min. This activation was blocked by protein kinase C (PKC) inhibitor (G6976), G protein inhibitor (GDPs), and MEK(MAPK/extracellular signal regulated kinase kinase) inhibitor(PD98059), but not by protein kinase A (PKA) inbibitor (H89), tyrosine kinase inhibitor (genistein), and glucocorticoid receptor (GR) antagonist (RU3.486). Thus, the rapid activation of Erk1/2 MAPK in primary hippocampal cells induced by B was likely mediated by a G protein coupled receptor (GPCR) pathway with involvement of PKC, which belonged to the nongenomic rather than genomic mechanism of GC's effects.

关键词： glucocorticoid MAPK rapid effects nongenomic mechanism.