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中华妇产科杂志 2015年第5期50卷 367-373页

作者：任虹任国丽孙丽敏范秀华王钰然李晓茜河北医科大学第二医院妇产科石家庄050000 河北省元氏县人民医院妇产科河北省正定县人民医院妇产科

目的：探讨感染期子宫颈癌U14细胞荷瘤小鼠巨噬细胞分泌CC型趋化因子配体5（CCL5）受到抑制的机制。方法取6~8周龄的雌性C57BL/6小鼠随机（采用随机数字表法）分为4组，每组6只。无瘤组：皮下注射DMEM培养基；荷瘤组：皮下注射子宫颈癌... 详细信息

目的：探讨感染期子宫颈癌U14细胞荷瘤小鼠巨噬细胞分泌CC型趋化因子配体5（CCL5）受到抑制的机制。方法取6~8周龄的雌性C57BL/6小鼠随机（采用随机数字表法）分为4组，每组6只。无瘤组：皮下注射DMEM培养基；荷瘤组：皮下注射子宫颈癌细胞系U14细胞；无瘤＋脂多糖（LPS；用于诱导小鼠感染）组：皮下注射DMEM培养基，腹腔内注射LPS；荷瘤＋LPS组：皮下注射U14细胞，腹腔内注射LPS。（1）采用ELISA法及荧光定量PCR技术检测各组小鼠血清及巨噬细胞中CCL5和前列腺素E2（PGE2）的表达。（2）提取各组荷瘤小鼠血清制备肿瘤条件培养基（TCM），体外诱导巨噬细胞，检测诱导前、后各组上清液和巨噬细胞中CCL5、PGE2和环磷酸腺苷（cAMP）的表达。（3）荷瘤＋LPS组选用环氧合酶2（COX-2）抑制剂——NS398阻断PGE2的产生（即荷瘤＋LPS＋NS398组），蛋白激酶A（PKA）阻滞剂——H89阻断cAMP/PKA信号通路（即荷瘤＋LPS＋H89组），分别制备TCM并检测两组上清液和巨噬细胞中CCL5、PGE2和cAMP的表达。结果（1）荷瘤组小鼠血清中CCL5蛋白含量及巨噬细胞中CCL5 mRNA的表达水平[分别为（151±35）pg/ml、1.0]均明显低于无瘤组[分别为（691±85）pg/ml、4.5±0.8；P〈0.05]；其血清中PGE2蛋白含量及巨噬细胞中PGE2 mRNA的表达水平[分别为（1198±83）pg/ml、5.8±0.8]均明显高于无瘤组[分别为（187±25）pg/ml、1.0；P〈0.05]。无瘤＋LPS组小鼠血清中CCL5蛋白含量及巨噬细胞中CCL5 mRNA的表达水平[分别为（4049±141）pg/ml、31.5±2.0]均高于明显高于荷瘤＋LPS组[分别为（1951±71）pg/ml、12.1±2.8；P〈0.05]；其血清中PGE2蛋白含量及巨噬细胞中PGE2 mRNA的表达水平[分别为（676±70）pg/ml、3.4±0.4]均低于荷瘤＋LPS组[分别为（2550±382）pg/ml、11.6±0.9；P〈0.05]。（2）各组小鼠血清制备的TCM在体外培养巨噬细胞后，荷瘤组上清液中CCL5、PGE2、cAMP蛋白含量[分别为（1626±177）、（790±156）、（164±30）pg/ml]及巨噬细胞中CCL5、PGE2、cAMP mRNA的表达水平（分别为28.6±1.2、1.7±0.3、1.6±0.3）均明显高于无瘤组[其蛋白含量分别为（27±3）、（448±115）、（118±25）pg/ml，其mRNA的表达水平均为1.0；P〈0.05]。无瘤＋LPS组上清液中CCL5蛋白含量及巨噬细胞中CCL5 mRNA的表达水平[分别为（10475±742）pg/ml、212.0±5.7]均明显高于荷瘤＋LPS组[分别为（6375±530）pg/ml、142.3±2.5；P〈0.05]；无瘤＋LPS组上清液中PGE2、cAMP蛋白含量[分别为（2438±95）、（340±13）pg/ml]及巨噬细胞中PGE2、cAMP mRNA的表达水平（分别为4.3±0.7、4.1±0.4）均明显低于荷瘤＋LPS组[其蛋白含量分别为（3441±163）、（542±42）pg/ml，其mRNA的表达水分别为5.9±0.3、5.4±0.5；P〈0.05]。（3）与荷瘤＋LPS组比较，荷瘤＋LPS＋NS398组上清液中CCL5蛋白含量及巨噬细胞中CCL5 mRNA的表达水平[分别为（7691±269）pg/ml、159.0±8.9]明显升高（P〈0.05），而上清液中PGE2、cAMP蛋白含量及巨噬细胞中PGE2、cAMP mRNA的表达水平均明显降低（P〈0.05）；荷瘤＋LPS＋H89组上清液中CCL5蛋白含量及巨噬细胞中CCL5 mRNA的表达水平[分别为（8375±520）pg/ml、177.0±8.8]进一步升高（P〈0.05），而上清液中PGE2、cAMP蛋白含量及巨噬细胞中PGE2、cAMP mRNA的表达水平均进一步降低（P〈0.05）。结论感染期子宫颈癌U14细胞荷瘤小鼠血清可在体外抑制巨噬细胞分泌CCL5，这种抑制效应可能是通过cAMP/PKA通路而受PGE2的调控。

关键词：宫颈肿瘤趋化因子CCL5 环AMP依赖性蛋白激酶类地诺前列酮环氧化酶2 肿瘤,实验性 Chemokine CCL5 cyclooxygenase 2

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Dietary arachidonate in milk replacer triggers dual benefits of PGE2 signaling in LPS-challenged piglet alveolar macrophages

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Journal of Animal Science and Biotechnology 2019年第2期10卷 435-448页

作者： Kathleen R.Walter Xi Lin Sheila K.Jacobi Tobias Kaser Debora Esposito Jack Odle Department of Animal Science Plants for Human Health InstituteNorth Carolina State UniversityKannapolisNorth CarolinaUSA Department of Animal Science North Carolina State UniversityRaleighNorth CarolinaUSA Department of Animal Science Ohio State UniversityColumbusOhioUSA Department of Population Health and Pathobiology College of Veterinary MedicineNorth Carolina State UniversityRaleighNorth CarolinaUSA.

Background: Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2(supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE2 effects merits ***: Day-old pigs(n = 60) were allotted to one of three dietary groups for 21 d(n = 20/diet), and received either a control diet(CON, arachidonate = 0.5% of total fatty acids), an arachidonate(ARA)-enriched diet(LC n-6,ARA = 2.2%), or an eicosapentaenoic(EPA)-enriched diet(LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and m RNA was isolated to assess markers associated with inflammation and eicosanoid *** media were collected to assess PGE2 secretion. Oxidative burst in macrophages was measured by: 1)oxygen consumption and extracellular acidification(via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS ***: Concentration of ARA(% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3(P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA(P < 0.0001), and PGE2 secretion(P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance(P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation(P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation(P < 0.001)and nitric oxide production(P < 0.002) were observed after 18 h of LPS stimulation but were unaffected by ***: We infer that enriching diets with arachidonic acid may be an ef

关键词： Arachidonic acid cyclooxygenase Eicosanoid Eicosapentaenoic acid Inflammation Lipid mediator class switch LPS Lipoxin Porcine alveolar macrophage

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Clinical Use of COX-2 Inhibitors Containing Quinoline Heterocycle as a Selective Therapeutic Agents for Complementary Medicine

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Clinical Complementary Medicine and Pharmacology 2023年第3期3卷 60-77页

作者： Megha P.Ambatkar Nilesh R.Rarokar Pramod B.Khedekar Department of Pharmaceutical Sciences Rashtrasant Tukadoji Maharaj Nagpur UniversityNagpurMaharashtra 440033India

Inflammation represents an initial response of immune system and is involved in a number of biochemical *** incidents may multiply and further develop the provocative *** the past 15 years,various classes of secondary metabolites that were isolated from plant and marine sources have been described as natural cyclooxygenase(COX)*** majority of natural COX inhibitors could be used as a selective therapeutic agent for complementary medicine and clinical ***,the inflammation is commonly treated by non-steroidal anti-inflammatory drugs(NSAIDs),several medications of which,however,have been linked to renal and gastrointestinal side effects.A variety of inhibitors of COX-2 that are selective(celecoxib,rofecoxib,valdecoxib and others)have been designed as NSAIDs mostly with enhanced stomach safety *** helps to improve the compliance and functions in the geriatric patients as they have so many complications and problems associated with the *** use of complementary medicine in combination with clinical therapy might give better results than medicine *** disease condition like cancer which shows the COX-2 expressions could also have treatment related problems in such cases the selective inhibitors used as a complementary *** the other hand,elevated cardiovascular risks have brought increasing worries about the safety of using specific inhibitors of *** current review focuses on how quinoline heterocycle was used for creation of inhibitors of COX-2 since 2009 along with its clinical significance in complementary *** agents included the variety of substituents on the ring or ring attached to other *** a result,the quinoline heterocycle will be used for creating and finding anti-inflammatory COX-2 medicines.

关键词： Quinoline Heterocycle Inflammation cyclooxygenase Natural Complementary NSAID COX-2 inhibitor

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OBSERVATION ON EFFECTS OF DRUGS ON TWO MAJOR METABOLIC PATHWAYS OF ARACHIDONIC ACID BY USING RAT PLEURAL NEUTROPHILS

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Chinese Science Bulletin 1988年第10期33卷 866-871页

作者：岳天立麦凯 Department of Pharmacology Faculty of Pharmacy Second Military Medical University CPLA Shanghai

Prostaglandins (PG) and leukotrienes (LT) are two major groups of products with potent biological activities, generated from arachidonic acid (AA) via cyclooxygenase (CO) pathway and 5-lipoxygenase (5-LO) pathway, respectively. Since these products are involved in various pathological processes, such as inflammation, thrombosis and allergy, considerable attention has been given to them. In order

关键词： lipoxygenase allergy cyclooxygenase inflammation potent ACID ethanol inhibited manner assessed

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Molecular Analysis of Clerodendrum formicarum Effects in Painful Diabetic Neuropathy in Rat

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World Journal of Neuroscience 2015年第4期5卷 258-269页

作者： Ghislain Loubano-Voumbi Mor Diaw Valentin Ouedraogo Abdou Khadir Sow Aissatou Seck Luc Magloire Anicet Boumba Abdoulaye Ba Abdoulaye Samb Laboratory of Physiology and Functional Exploration Faculty of Medicine of Pharmacy and OdontologyCheikh Anta Diop University of DakarDakarSenegal Laboratory of Molecular Biology of the Loandjili Hospital Pointe NoireRepublic of Congo

The pathophysiology of diabetic neuropathic pain is due to primarily metabolic and vascular factors. There is an increase in sorbitol and fructose, glycated end products, reactive oxygen species and activation of protein kinase C in the diabetic state. All these factors lead to direct damage to the nerves. Taking effective clinical management of neuropathic pain is based on a pharmacological treatment that has shown their limits and many side effects. The hypothesis of central sensitization inhibited by Clerodendrum formicarum, an African pharmacopoeia plant used to treat headaches, arthritis, epilepsy and chronic pain could act on astrocytes and microglial cells. The objective of this work is to study the effect of Clerodendrum formicarum (100, 150 and 200 mg/kg body weight) on astrocytes and microglial cells in a model of diabetic neuropathic pain induced by alloxan monohydrate (150 mg/kg). We noted a suppression of mechanical allodynia and mechanical hyperalgesia respectively by the Von Frey filaments test and the pressure test on the paw by the Clerodendrum formicarumextracts (ECF) at different doses from 2 h at the first injection of the ECF. After 5 days of treatment, we expressed by Western Blot bands of different proteins and by quantitative RT-PCR, we determined inhibition of the expression of GFAP, CD11b and isoforms 1 and 2 of cyclooxygenase. These results suggest that ECF inhibits the activation of astrocytes, microglial cells and cyclooxygenase signaling pathway.

关键词： Clerodendrum formicarum Astrocytes Microglial Cells Diabetic Neuropathy Pain cyclooxygenase

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Subject Index

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China Medical Abstracts(Internal Medicine) 2009年第4期26卷 234-262页

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Antioxidant and Anti-Inflammatory Effects of Peanut Skin Extracts

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Food and Nutrition Sciences 2013年第8期4卷 22-32页

作者： Wanida E. Lewis Gabriel K. Harris Timothy H. Sanders Brittany L. White Lisa L. Dean Department of Food Bioprocessing and Nutrition Sciences North Carolina State University Raleigh USA Market Quality and Handling Research Unit Agricultural Research Service United States Department of Agriculture Raleigh USA Market Quality and Handling Research Unit Agricultural Research Service United States Department of Agriculture Raleigh USA.

Peanut skins are regarded as a low economic value by-product of the peanut industry;however, they contain high levels of bioactive compounds including catechins and procyanidins, which are known for their health-promoting properties. The in vitro antioxidant activity of peanut skin extracts (PSE) has been reported but the associated anti-inflammatory properties have not been widely examined. This study investigated the anti-inflammatory effects of PSE on the pro-inflammatory enzyme, cyclooxygenase-2 (COX-2) protein expression, on its downstream product, prostaglandin E2 (PGE2), and on nitrous oxide (NO) levels. Defatted peanut skins were extracted using two aqueous solvent mixtures (50% acetone and 90% ethanol), in order to compare the effects of the two solvent systems on antioxidant and anti-inflammatory properties. PSE antioxidant activity was determined by the hydrophilic oxygen radical absorbance capacity (H-ORAC) assay, while total phenolics were determined by the Folin-Ciocalteu assay and flavan-3-ols and procyanidins were quantified by HPLC. Acetone extracted PSE (A-PSE) exhibited numerically, but not statistically higher H-ORAC and total phenolic values than the ethanol extracted PSE (E-PSE) (1836 μmol Trolox/100 g and 67.9 mg GAE/g, and 1830 μmol Trolox/100 g and 51.8 GAE/g respectively). A-PSE also had higher levels of flavan-3-ols and procyanidins than E-PSE. RAW 264.7 cells were pretreated with 1.0%, 2.5% and 5.0% (v/v) of A-PSE or E-PSE and induced with the inflammatory marker, lipopolysaccharide (LPS) for 12 hours. COX-2 protein expression, measured by Western blotting was significantly (p 2 and NO levels measured by ELISA, were significantly (p < 0.05) decreased with increasing added levels of A-PSE and E-PSE suggesting that A-PSE and E-PSE not also possess similar antioxidant properties, but also exhibit similar anti-inflammatory effects.

关键词： Peanut Skins Antioxidants Anti-Inflammatory cyclooxygenase (COX-2) Prostaglandin E2 (PGE2) Nitric Oxide (NO) Procyanidins

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Molecular Docking and ADMET Study of Emodin Derivatives as Anticancer Inhibitors of NAT2, COX2 and TOP1 Enzymes

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Computational Molecular Bioscience 2017年第1期7卷 1-18页

作者： Daniel M. Shadrack Valence M. K. Ndesendo Chemistry Department Faculty of Natural and Applied Sciences St. John’s University of Tanzania Dodoma Tanzania Department of Pharmaceutics and Formulation Sciences School of Pharmacy and Pharmaceutical Sciences St. John’s University of Tanzania Dodoma Tanzania

Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was carried out to evaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2, cyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics and explore their bonding modes. Molecular docking study suggested that D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested to be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind to the same pocket with different binding conformation. Pharmacokinetic study suggested that selected emodin derivatives can be potential cancer chemotherapeutic agent. Physicochemical parameters such density, balaban index, surface tension, logP and molar reflectance correlated to compounds activity. These finding provides a potential strategy towards developing NAT2 and TOP1 inhibitors.

关键词： Human Arylamine N-Acetyltransferase 2 (NAT2) cyclooxygenase 2 (COX2) Topoisomerase 1 (TOP1) Emodin In Silico Inhibition Pharmacokinetics Molecular Docking

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S(+)-Flurbiprofen Shows Potent PGE2 Inhibitory Activity in Inflammatory Cells, Superior Cell Transport Activity and Skin Permeability

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Pharmacology & Pharmacy 2016年第8期7卷 305-312页

作者： Yoshihisa Toda Masanori Sugimoto Hiromi Endo Miho Kamezawa Ichimaro Yamada Shogo Kawabata Shinsuke Kaku Noboru Otsuka Hideo Matsumoto Research Headquarters Taisho Pharmaceutical Co. Ltd. Saitama Japan Mitsubishi Tanabe Pharma Corporation Tokyo Japan Research Department Tokuhon Corporation Saitama Japan Development Headquarters Taisho Pharmaceutical Co. Ltd. Tokyo Japan Institute for Integrated Sports Medicine Keio University School of Medicine Tokyo Japan

We developed a novel topical non-steroidal anti-inflammatory drug (NSAID)patch, S(+)-flurbiprofen plaster, (SFPP), containing S(+)-flurbiprofen (SFP), an enantiomer of flurbiprofen (FP). In a previous study conducted in an animal model, we showed good skin absorption and potent analgesic efficacy of SFPP. In this study, to examine the superior features, as an NSAID patch, of SFP as compared to FP and R(-)-flurbiprofen (RFP), we tested the stereospecificity of SFP actions on Prostaglandin E2 (PGE2) inhibition in rat inflammatory leukocytes and in the binding activity of the drug to cells, and also the in vitro skin permeability of the drug in the Yucatan micropig (YMP). SFP showed potent inhibitory activity on PGE2 production from peritoneal leukocytes stimulated with a bacterial suspension, as compared to RFP and FP. The half maximal (50%) inhibitory concentration (IC50) values were 14 nM for SFP, 52 nM for FP, and 17,000 nM for RFP. In the cell binding study, significant and rapid increase of SFP binding to polymorphonuclear leucocytes (PMNs) was observed at 5 min after incubation, eventually reaching a steady state. SFP showed significantly higher binding activity for the inflammatory leucocytes as compared to RFP, suggesting its superior transfer potency. The skin permeability profile of SFP, RFP and FP in the YMP model showed that the rank order of the cumulative amount of permeated compounds in the skin was SFP > RFP > FP. The steady-state permeation rate (Flux) of SFP was significantly higher than that of FP (4.89 and 1.55 mg/cm2/h, respectively, p = 0.0068), indicating the remarkably superior skin permeability of SFP. SFP exerted potent inhibitory activity on PGE2 production and superior binding activity to the PMNs and skin permeability, as compared to FP and RFP. These results suggest that SFP possesses favorable characteristics for use as an active ingredient in the NSAID patch.

关键词： NSAIDs S(+)-Flurbiprofen cyclooxygenase Skin Permeability

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Mechanism research and effect of ulinastatin in the brain tissue injury of acute hydrogen sulfide intoxicated rats

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China Medical Abstracts(Internal Medicine) 2016年第2期33卷 10-11页

作者：周觉 Emerg Med Center1st Affil HospWenzhou Med Coll

Objective To observe the effect of Ulinastatin(UTI)in the dynamic changes of aquaporin 4(AQP4)and cyclooxygenase-2(COX-2)in the brain tissue injury of acute hydrogen sulfide(H2S)intoxicated,to explore

关键词： sulfide aquaporin cyclooxygenase creased edema exposure posed slight degen behavioral

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