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Transcriptional down regulation of hTERT and senescence induction in HepG2 cells by chelidonine

World Journal of Gastroenterology 2009年第29期15卷 3603-3610页

作者： Sakineh Kazemi Noureini michael wink Department of Biology Faculty of Basic Science Tarbiat Moallem University of Sabzevar Sabzevar Iran Department of Biology Institute of Pharmacy and Molecular Biotechnology Heidelberg University INF 364 69120 Heidelberg Germany

AIM: To investigate the potential effects of chelidonine, the main alkaloid of Chelidonium majus, on telomerase activity and its regulation in HepG2 cells. METHODS: Cytotoxicity of chelidonine for HepG2 cells was determined by neutral red assay. A modified polymerase chain reaction (PCR)-based telomerase repeat amplification protocol was used to estimate relative telomerase activity in chelidonine-treated cells in comparison with the untreated control cells. Relative expression level of the catalytic subunit of telomerase (hTERT) gene and P-glycoprotein (pgp) were estimated using semi-quantitative real-time reverse transcription-PCR (RT-PCR). Cell senescence in treated cells was demonstrated using a β-galactosidase test. RESULTS: Cytotoxicity of chelidonine in HepG2 cells was not dose-dependent and tended to reach plateau immediately after the living cells were reduced in number to slightly higher than 50%. However, 12 μmol/L concentration of chelidonine was considered as LD50, where the maximal attainable effects were realized. Real-time RT-PCR data showed that the expression of pgp increased three-fold in chelidonine treated HepG2 cells in comparison with the untreated controls. Morphologically, treated HepG2 cells showed apoptotic features after 24 h and a small fraction of cells appeared with single blister cell death. The relative expressionlevel of Bcl-2 dropped to less than 50% of control cells at a sub-apoptotic concentration of chelidonine and subsequently increased to higher than 120% at LD50. Telomerase activity was reduced considerably after administration of very low doses of chelidonine, whereas higher concentrations of chelidonine did not remarkably enhance the effect. Real-time RT-PCR experiments indicated a drastic decrease in expression level of hTERT subunit of telomerase under treatment with chelidonine. Repeated treatment of cells with very low doses of chelidonine caused a decline in growth rate by 4 wk and many of the cells appeared to be aged

关键词： HepG2细胞 hTERT 转录调控白屈菜诱导衰老碱

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Expanding the Therapeutic Spectrum of Artemisinin:Activity Against Infectious Diseases Beyond Malaria and Novel Pharmaceutical Developments

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World Journal of Traditional Chinese Medicine 2016年第2期2卷 1-23页

作者： Thomas Efferth Marta R.Romero Anna Rita Bilia Ahmed Galal Osman Mahmoud ElSohly michael wink Rudolf Bauer Ikhlas Khan Maria Camilla Bergonzi Jose J.G.Marin Department of Pharmaceutical Biology Institute of Pharmacy and Biochemistry Johannes Gutenberg University Experimental Hepatology and Drug Targeting (HEVEFARM) CIBERehd IBSAL University of SalamancaCampus Miguel de Unamuno Department of Chemistry "Ugo Schiff" University of Florence National Center for Natural Products Research School of Pharmacy University of Mississippi ElSohly Laboratories Inc. Department of Pharmaceutics University of Mississippi Institute of Pharmacy and Molecular Biotechnology Ruprecht-Karls University Institute of Pharmaceutical Sciences Department of Pharmacognosy University of Graz Devision of Pharmacognosy Department of Biomolecular Sciences University of Mississippi

The interest of Western medicine in Traditional Chinese Medicine(TCM) as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCM over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin(qinghaosu), which is extracted from the medicinal plant Artemisia annua L.(qinghao). The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCM. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives(artemisinins) exert profound activities towards other protozoans(Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella), trematodes(Schistosoma, liver flukes), and viruses(human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives(artesunate, artemether, arteether), novel drug development strategies have been *** included the synthesis of acetal-and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, ***-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in addition to the advancement in

关键词： Artemisinin derivatives Artemisia annua Asteraceae Antimalarial drugs Anti-pathogen activity Antiviral properties Artemisinin-loaded nanocarriers Traditional Chinese Medicine

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Natural Products Modulate the Multifactorial Multidrug Resistance of Cancer

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Pharmacology & Pharmacy 2015年第3期6卷 146-176页

作者： Safaa Yehia Eid Mahmoud Zaki El-Readi Sameer Hassan Fatani Essam Eldin Mohamed Nour Eldin michael wink Department of Biochemistry Faculty of Medicine Umm Al-Qura University Makkah Kingdom of Saudi Arabia Institute of Pharmacy and Molecular Biotechnology Heidelberg University Heidelberg Germany Department of Biochemistry Faculty of Pharmacy Al-Azhar University Assiut Egypt

Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated compounds. Several mechanisms can mediate the development of MDR, including increased drug efflux from the cells by ABC-transporters (ABCT), activation of metabolic enzymes, and defective pathways towards apoptosis. Many plant secondary metabolites (SMs) can potentially increase sensitivity of drug-resistant cancer cells to chemotherapeutical agents. The present thesis investigates the modulation of MDR by certain medicinal plants and their active compounds. The inhibition of ABCTs (P-gp/MDR1, MRP1, BCRP) and metabolic enzymes (GST and CYP3A4), and the induction of apoptosis are useful indicators of the efficacy of a potential medicinal drug. The focus of this study was the possible mechanisms of drug resistance including: expression of resistance proteins, activation of metabolic enzymes, and alteration of the apoptosis and how to overcome their resistance effect on cancer cells. The overall goal of this review was to evaluate how commonly used medicinal plants and their main active secondary metabolites modulate multidrug resistance in cancer cells in order to validate their uses as anticancer drugs, introduce new therapeutic options for resistant cancer, and facilitate the development of their anticancer strategies and/or combination therapies. In conclusion, SMs from medicinal plants exhibit multitarget activity against MDR-related proteins, metabolic enzymes, and apoptotic signaling, this may help to overcome resistance towards chemotherapeutic drugs.

关键词： Multidrug Resistance (MDR) ABC-Transporters (ABCT) Metabolic Enzymes Apoptosis CytochromeP3A4 (CYP3A4) Glutathione-S-Transferase (GST)

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燕雀亚科鸟类的贝叶斯系统发生:非洲鹂雀的分类地位及朱雀属的进化与异质起源(英文)

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动物学报 2007年第5期53卷 826-834页

作者： Antonio ARNAIZ-VILLENA Juan MOSCOSO Valentin RUIZ-DEL-VALLE Javier GONZALEZ Raquel REGUERA michael wink Juan I.SERRANO-VELA Department of Immunology Universidad ComplutenseThe Madrid Regional Blood Center Institut für Pharmazie und Molekulare Biotechnologie-Abteilung Biologie Universitt Heidelberg

鹂雀(Linurgus olivaceus)是非洲热带森林中一种独特的鸣禽,为鹂雀属(Linurgus)的惟一物种。在已有的研究中,通过对鹂雀和雀形目现存鸟类中每个科及亚科至少一个物种的线粒体DNA序列测定,分析了鹂雀与其它现存雀形目鸟类的系统发生关系... 详细信息

鹂雀(Linurgus olivaceus)是非洲热带森林中一种独特的鸣禽,为鹂雀属(Linurgus)的惟一物种。在已有的研究中,通过对鹂雀和雀形目现存鸟类中每个科及亚科至少一个物种的线粒体DNA序列测定,分析了鹂雀与其它现存雀形目鸟类的系统发生关系;在遗传上,对鹂雀与金丝雀、金翅雀及燕雀亚科其它鸟类亦有比较研究。本研究共使用了燕雀亚科83种鸟类,重点对该亚科的系统发生进行了修订。使用贝叶斯法构建了系统发生树,结果表明:鹂雀属于燕雀亚科,系统发生树中聚在金翅雀族(Carduelini),与金丝雀属(Serinus)、金翅雀属(Carduelis)及交嘴雀属(Loxia)的种类形成一组;在系统发生中,鹂雀可能是一个基部物种,它同金丝雀属和金翅雀属鸟类一同进化并分歧出来。在本研究中未能涉及的一些已灭绝种类,可能与鹂雀有着较近的遗传学关系。另一方面,研究也表明锡嘴雀(Coccotharustes coccothraustes)肯定包括在欧亚蜡嘴雀(蜡嘴雀属Eophona和拟蜡嘴雀属Mycerobas)中,美洲的朱雀(Carpodacus)可能是从亚洲种类分歧出来并经过进化辐射形成。

关键词：朱雀锡嘴雀蜡嘴雀家朱雀鹂雀雀形目鸣禽

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