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Doxorubicin (Dox) is an effective wide-spectrum antitumor drug. However, its clinical application may be hampered by dose-dependent cardiotoxicity. The mechanisms of cardiotoxicity have not been clearly elucidated, but are known to involve oxidative stress, mitochondrial dysfunction and apoptosis. Autophagy is a lysosome-dependent protein degradation pathway. More recently, many studies have suggested that autophagy plays an important role in Dox-induced cardiotoxicity. This paper gives a systematic review of the role of autophagy in Dox-induced cardiotoxicity. © 2017 Chinese Journal of Pharmacology and Toxicology. All rights reserved. 相似文献
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Rutin is extracted from Ruta graveolens L. with many pharmacological activities such as anti-inflammation, anti-oxidation , protecting cardiovascular system and analgesia. As a natural product, rutin has the advantages of low side effects and difficult tolerance, but its instability and low bioavailability still limit its clinical application. This paper summarizes the analgesic mechnism of rutin, and looks forward to the clinical applica¬tion of rutin based on its derivative and dosage forms. It is expected to provide ideas for further analgesic research and drug development and application of rutin in the future. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
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Deng X. Meng D. Wu J.-Y. Jiang B.-T. Yang Y.-Y. Zhang Y.-Q. Zhao Y. Huang F. Che Y.-Y. 《中国药理学通报》2023,(9):1696-1704
Aim To elucidate the effect of corilagin (Cor) on cholesterol metabolism in macrophages and the underlying mechanism. Methods Molecular docking was applied to predict the protein target of Cor on cellular cholesterol metabolism. The RAW264.7 macrophage foam model induced by 80 mg • L-1 oxidized low density lipoprotein (ox-LDL) was established to evaluate the activity of Cor on lowering-cholesterol. The expression of genes and proteins related with cholesterol metabolism were detected by q-PCR and Western blotting,respectively. Then the activity of Cor on lipid metabolism was validated in ApoE mice fed with high-fat-diet. Results Cor and Class A Scavenger receptor (SRA), CD36, peroxisome proliferator-activated receptor γ (PPAR-γ), ATP binding cassette transporter Gl(ABCGl), which associated with cholesterol metabolism, could form hydrogen bonds and hydrophobic interactions. Cell experiments showed that Cor (60,120 and 240 μmol • L-1) significantly decreased TC content in macrophages, Cor could down-regulate SRA and CD36 gene expression, SRA protein expression, up-regulate the expression of ABCA1 and ABCG1 genes. Animal experiments demonstrated that Cor (15,30 and 60 mg • k g - 1 ) could decrease the serum TMAO content, the plaque area and formation of foam cells in the aortic root,the expression levels of CD36 and SRA fluorescent proteins in aortic root plaques. Conclusions Cor could inhibit the formation of macrophage foam cells through the regulation of cholesterol metabolism mediated by CD36,SRA, ABCA1 and ABCG1 to cure the AS. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
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Lyu C.Hou Z.-H.Wei Y.-B.Feng J.-H.Di Y. 《中国药理学通报》2015,(12):1652-1655
RAGE (receptor for advanced glycation end products) is a multiligand receptor on the cell surface. Ligand-RAGE interactions activate several signal transduction pathways that propagate cellular oxidative stress and inflammatory response. RAGE expressed on the CD4+ T cells has been identified as a central transduction receptor which affects the activation, proliferation, migration and differentiation of the cells. In addition, blockade of RAGE suppressed the development of multiple immune-related disorders mediated by CD4+ T cells. These studies highlight the importance of RAGE and its ligands for CD4+ T cells. This article briefly reviews the role of RAGE and its ligands on the proliferation, migration and differentiation of CD4+ T cells and summarizes the related research progress. 相似文献
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《中国药理学与毒理学杂志》2018,(11):830-834
2018年8月23-25日在江苏省连云港市举行了'网络药理学与生物医药发展国际论坛'。本次论坛由中国科协海智办、国际药理学联合会天然药物药理学分会、中国药理学会、中国药学会、江苏省科学技术协会、江苏省食品药品监督管理局、连云港市人民政府共同主办,中国药理学会网络药理学专业委员会承办. 相似文献
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Zhou K.-X.Xu L.-T.Ma Y.-J.Zhou J.-S.Dai J.-J.Liang L.-L.Wei H. 《中国药理学与毒理学杂志》2016,(11):1198-1205
With the extension of human life, the number of patients with Alzheimer disease (AD) is increaseing. However, the mechanisms of AD are still not very clear and there is no effective prevention and treatment process for this disease. In recent years, the importance of intestinal microbiota in the health field has been gradually elaborated, which has become a new research area for AD. There is chronic inflammation, a low level of neurotransmitter 5-hydroxy tryptamine and neurotrophic factor in the central nervous system of AD patients, and a changed structure of AD intestinal microbiota. The intestinal microbiota can cause chronic inflammation, produce neurotoxic substances, and may be related to obesity, type 2 diabetes and other metabolic diseases which are AD high-risk disease, suggesting the correlation between AD and intestinal microbiota. Intestinal microbiota can be regulated by probiotics, prebiotics and traditional Chinese materia medica and beneficial microbiota can reduce inflammation and the occurrence of metabolic syndrome such as diabetes, increase the level of brain neurotransmitter 5-hydroxytryptamine and neurotrophic factor and improve cognitive function. Intestinal microbiota regulation may become a new approach to the prevention and treatment of AD. 相似文献
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Aim To explore the inhibitory effect of isobavachalcone ( IBC) on migration and invasion of tongue squamous cell carcinoma Tca8113 cells and its possible mechanism. Methods Tca8113 cells were treated in different concentrations of IBC in vitro. Cell proliferation was detected by MTT; Wound healing assay and Transwell chamber assay were used to detect the ability of cell migration and invasion; Western blot was applied to detect the expression of Akt, p-Akt, MMP-2 and MMP-9 proteins. Results IBC could inhibit the proliferation of Tca8113 cells in a concentra-tion-and time-dependent manner. IBC can reduce cell migration and invasion. Western blot showed that IBC could an decrease the expression of p-Akt, MMP-2 and MMP-9 proteins in a concentration- dependent manner. However, the level of Akt was not affected by the concentration of IBC treatment. Conclusion IBC could inhibit the proliferation, migration and invasion in Tca8113 cells and its mechanism may be associated with the down-regulation of MMP-2 and MMP-9 proteins and the inhibition of phosphorylation of upstream Akt. 相似文献
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Aim To investigate the effects of cimifugin on mouse atopic dermatitis (AD) induced by fluorescein isothiocyanate (FITC) and further explore the mechanism of its action. Methods ICR mice were randomly divided into blank group, model group, positive group (dexamethasone),low dose group,high dose group and administration group of cimifugin. FITC solution was applied to the shaved abdomen of mice in the sensitization stage, and 0.6 % FITC solution was applied to attack the ears of mice in the stimulation stage. The administration groups were given medicine for seven consecutive days. The effects of cimifugin on body weight, thymus index and spleen index of mice were detected. Ear inflammatory cell infiltration was observed by HE staining. The ear swelling of mice was measured, and Th2 cytokines IL-5,IL-13 and the key promoter of allergy IL-33 were detected by ELISA. The epithelial barrier structural proteins, filaggrin, claudinl,occludin and E-cadherin,were detected by immunohistochemistry and Western blot. Results Compared with the blank group, the model group showed significant AD symptoms. Compared with the model group, cimifugin transdermal administration group significantly reduced ear inflammatory cell infiltration,ear swelling, IL-5,IL-13 and IL-33, and significantly increased the expression of filaggrin and occludin. Conclusions Transdermal administration of cimifugin could significantly inhibit AD in mice, and its mechanism involves repairing epithelial barrier function, restoring filaggrin and occludin, inhibiting allergy promoting factor IL-33, and finally inhibiting AD inflammation. © 2023 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
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Jian Y.Chen L.Yuan M.Zhuang X.-M.Li H. 《中国药理学与毒理学杂志》2016,(8):848-854
OBJECTIVE: To investigate enzyme kinetic characteristics of imperatorin in rat liver microsomes (RLM) or human liver microsomes (HLM), and to identify the reaction phenotyping of human recombinant cytochrome P450 enzyme (CYP) mediated phase I metabolism. METHODS: Imperatorin was incubated at 37°C with HLM or RLM in the presence or absence of nicotinamide adenine dinucleotide phosphate (NADPH) or uridine 5'-diphosphoglucuronic acid (UDGPA). The concentrations of imperatorin in the incubation systems were determined with LC-MS/MS to evaluate its metabolic stability and enzymatic kinetics. The CYP phenotyping of imperatorin was identified using a panel of human recombinant CYP isoforms (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) and also using a group of specific inhibitors in HLM. RESULTS: Imperatorin was metabolically eliminated in the presence of NADPH in HLM or RLM. The elimination rates for HLM and RLM in 30 min were 69.7% and 94.5%, respectively, and elimination half-life (t1/2) values were 18.9±0.6 and (2.8±0.4)min, respectively. The extrapolated hepatic clearance parameters (Clh) were 16.9±0.1 and (51.9±0.4)mL·min-1-kg-1. The Michaelism-Menten parameters (Km) were 13.60±0.16 and (14.00± 0.24)umol·L-1 and maximum velocity (Vmax) were (2928±96) and (8434±27)nmol·min-1·g-1, respectively. The metabolic elimination of imperatorin in RLM was quicker than in HLM. The results of CYP phenotyping indicated that CYP1A2, CYP2B6, CYP2C19 and CYP3A4 were the major CYP isoforms involved in the imperatorin metabolism. Their individual contributions assessed using the method of total normalized rate were 20.4%, 7.3%,10.5% and 61.8%, respectively. CONCLUSION: Imperatorin is mainly eliminated by CYP mediated metabolism in HLM and RLM. CYP1A2 and CYP3A4 are the major responsible enzymes with a contribution rate above 20%. 相似文献
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《中国药理学通报》2023,(7):F0004-F0004
本刊免费全文开放存取网址:http://www.zgylxtb.cn;还可查阅http://yaol.chinajournal.net.cn(中国知网);http://zgylxtb.periodicals.net.cn(万方数据),及维普数据。从1999年起,本刊连续获中国科学技术协会和国家自然科学基金专项资金资助。2006~2018年获中国科协精品期刊工程示范项目及学术创新引领项目资金资助。本刊荣获第1、第2届国家科技部、中共中央宣传部、国家新闻出版署优秀科技期刊二等奖(1992、1997;后停办);第2、第3届国家期刊奖百种重点期刊奖(2003,2005)。 相似文献
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心肌梗死后抑郁(depression after myocardial infarction,DAMI)临床发病率较高,对患者的身心健康造成较大危害,但发病机制尚不清楚。采用能模拟人类DAMI发病原因和生物学反应的动物模型进行基础研究,是探索疾病机制的有效途径。该文将动物选择、模型选择、模型制备、行为学评价等建模过程中存在的问题进行总结和思考,以期为DAMI的模型研究提供参考。 相似文献
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Aim To investigate the effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression in nude mice bearing colorectal cancer. Methods Male BALB/C nude mice were inoculated with human colon cancer cell HT-29 under the armpit. The tumor bearing nude mice were randomly divided into five groups: control group, chemotherapy group, positive drug group, Lulong Zaisheng Decoction II groups with high and low doses. The mice were given drugs by gavage once a day for 10 consecutive days. From the fourth day of the experiment, except for the control group, the nude mice were intraperitoneally injected with 5-FU at dose of 25 mg • kg-1 for 7 consecutive days. The mice in control group were injected with the same volume of normal saline. On the 11th day, blood was collecled from the orbit to measure peripheral hemogram. The mice were killed after cervical dislocation, then the morphology of bone marrow cells was observed - Bone marrow cell cycle, apoplosis rate and CD34+ were detected by flow cytometiy, mRNA expressions of granulocyle-macrophage colony stimulating factor (GM-CSF), granulocyte-macrophage colony stimulating factor receptor (GM-CSFR), inlerleukin-1 p (IL-1 (3) and inlerleukin-3 (IL-3) were tested by quantitative real-lime PCR, and the protein expressions of vascular endothelial growth factor (VEGF) and intercellular cell adhesion molecule-1 (VCAM-1) were tested by Western blot. Results Lulong Zaisheng Decoction II significantly elevated the number of white cells, increased the proportion of CD34 positive cells and the percentage of S cells, and reduced the apoplosis rate of bone marrow cells. Furthermore, it obviously up-regulated the mRNA expressions of GM-CSF, GM-CSFR, IL-1 (3 and IL-3, and promoted the protein expressions of VEGF and VCAM-1 in bones. Conclusions Lulong Zaisheng Decoction II can significantly alleviate bone marrow suppression caused by chemotherapy. Its mechanism is closely related to regulating cell cycle, preventing bone marrow cell apoptosis, promoting the secretion and expression of hematopoietic growth factors, and improving bone marrow hematopoietic microenvironment. © Food and Fermentation Industries. All rights reserved. 相似文献
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