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The Chinese Phytotherapy: Oriental and Western Pathophysiological Aspects and Perspectives: the Example of Ephedrae Decoctum

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The Chinese Phytotherapy: Oriental and Western Pathophysiological Aspects and Perspectives: the Example of Ephedrae Decoctum THE CHINESE PHYTOTHERAPY: ORIENTAL AND WESTERN PATHOPHYSIOLOGICAL ASPECTS AND PERSPECTIVES: THE EXAMPLE OF EPHEDRAE DECOCTUM HELENA CRISTINA MENDES SOARES Dissertação de Mestrado em Medicina Tradicional Chinesa 2010 1 HELENA CRISTINA MENDES SOARES THE CHINESE PHYTOTHERAPY: ORIENTAL AND WESTERN PATHOPHYSIOLOGICAL ASPECTS AND PERSPECTIVES: THE EXAMPLE OF EPHEDRAE DECOCTUM Dissertação de Candidatura ao grau de Mestre em Medicina Tradicional Chinesa submetida ao Instituto de Ciências Biomédicas de Abel Salazar da Universidade do Porto. Orientador - Professora Doutora Paula Cristina Branquinho de Andrade Categoria - Professora Auxiliar com Agregação Afiliação - Faculdade de Farmácia da Universidade do Porto Co-orientador - Professor Doutor Henry Joahnnes Greten Categoria - Professor Associado Afiliação - Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto. ii Ackno wlegments “Words are never enough when it comes to state what goes on beyond the soul.” Just like now… This is so much more than an academic work: it contains a personal goal that would have never been achieved without the dedication, effort and friendship of a considerable number of people. To thank and to stress the contribution of all of them is of the most elementary justice, but also one of the most difficult of tasks. Moreover, I lack the ―art‖ to write all I wanted, and so the expression of my deepest gratitude to all shall be my commitment, dedication and friendship along every step of the journeys that are to come. It is with great pride that my first words of appreciation are addressed to my supervisors, who opened the doors of science to me, and inspired and guided me throughout this work. Thank you Professor Paula Andrade. Thank you for your cheerful mood, support, confidence - and, above all, for never letting this ―dream‖ collapse. I was honoured to have you as my supervisor. Thank you Professor Joahnnes Greten. Thank you for being my Master, for opening the doors to the wonderful science of Traditional Chinese Medicine. This thesis would certainly not have the same value without your experience and invaluable advice. Thank you, Professor Frank Brazkiewicz. For all the support: you have always been there for me. Thank you so much! To Professor Patrícia Valentão, all my best thanks. Your help was undeniable. I would also like to thank my husband, Rui. Thank you for everything: for believing in me ... for your dedication... for your patience. This work is also yours. Without your support, it would have been impossible. To my colleagues and friends, José Neves and Xuan, for all the help with the literature and translation: your contribution was essential. Thank you very much. Thank you to my friends and road companions on this journey throughout Chinese Medicine, António, Maria João, Anusca and Ricardo, for their support and enthusiasm, despite the odds. Father, mother... Thank you for giving me freedom of choice and believing in me. Without you, none of this would make any sense ... To you I dedicate all. iii Abbreviations 11-β-OHSD - 11-β-hydroxysteroid dehydrogenase 3MGA - 3β-monoglucuronyl-18β-glycyrrhetic acid A1C - glycated hemoglobin or HbA1c ACO - acyl-CoA oxidase ADP - adenosine diphosphate AGE - advanced glycationend product ALB - albumin ALT - alanine aminotransferase AMPK - AMP-activated protein kinase AST - aspartate transaminase/Aspartate aminotransferase ATP - adenosine triphosphate AUC - area under the plasma curve BUN - blood urea nitrogen CAM - complementary and alternative medicine CC - Cinnamomum cassia CCL - CC chemokine ligand CD36 - fatty acid transporter CE - cinnamon water extract CECs - cerebral endothelial cells CFS- chronic fatigue syndrome CHC - chronic hepatitis C CHM - Chinese herbal medicines CMV - cytomegalovirus CNS - central nervous system COX-2 - cyclooxygenase-2 CP - Chinese pharmacopoeia CPM - Chinese proprietary medicines Cr - creatinine Cyt-C - cytochrome C D-Gal N - galactosamine DGL - deglycyrrhizinated licorice DHEA - dehydroepiandrosterone DHS - dropped head syndrome DIN - Drug Identification Number DIO - diet-induced obesity iv DM - differentiated medium DPP-4 (DDP IV) - dipeptidyl peptidase IV EAT - Ehrlich ascites tumor EKG - electrocardiography ELISA - enzyme-linked immunosorbent assay EP - European pharmacopoeia ER - estrogen receptor ET-1- endothelin-1 FAS - fatty acid synthase FBG - fasting blood glucose FDA - Food and Drug Administration FER - food efficiency ratio FFA - free fatty acids FHF - fulminant hepatic failure fMRI - functional magnetic resonance imaging FST - forced swimming test GC - gas chromatography GC/MS- GC/mass spectrometry GEPRs - genetically epilepsy prone rats GER - gastric emptying rate GG - Glycyrrhiza glabra GGT - gamma-glutamyltransferase GLP-1- glucagon-like peptide-1 GLS - G. uralensis saponins GLU - glucose Glut4 - glucose transporting protein 4 GLUTs - hexose transporter protein GP - glycyrrhiza polysaccharide GPMT - guinea pig maximization test GRAS - Generally Recognised As Safe Grb2 - growth factorreceptor-binding protein 2 HbA1c - A1C or glycated hemoglobin (glycosylated hemoglobin A1c) HBsAg - hepatitis B surface antigen HC - hypercholesterolaemic animals HCC - hepatocellular carcinoma HDL- high-densitylipoprotein HDL-C - high-density lipoprotein cholesterol v HFD - high-fat diet HGG-I - hypercholesterolaemic animals administered with 5 gm% Glycyrrhiza glabra root powder HGG-II - hypercholesterolaemic animals administered with 10 gm% Glycyrrhiza glabra root powder; HIV - human immunodeficiency virus HMG-CoA - 3-hydroxy-3-methylglutaryl-coenzyme A HPLC - high performance liquid chromatography HPLC -DAD - high performance liquid chromatography with diode array detection IC50 - inhibitory concentration reducing activity to 50% of controls IFN - interferon IKS - Interkantonale Kontrollstelle fur Heilmittel IL-1β - interleukin-1β iNOS - inducible nitric oxide synthase IPGTT- intraperitoneal glucose tolerance test IR - insulin receptor IRS - insulin receptor substrate IRS -1 and IRS-2- insulin receptor substrate-1 and insulin receptor substrate-2 JP - Japanese pharmacopoeia LBD - ligand-binding domain LD50 - mean lethal dose (lethal dose killing 50% of animals) LDH - lactate dehydrogenase LDL - low-density lipoprotein LDL - low-density lipoprotein LDL-C - low-density lipoprotein cholesterol LicA - licochalcone A LPL - lipoprotein lipase LPS - lipopolysaccharide MHCP - methylhydroxychalcone polymer MIC - minimum inhibitory concentration MPA - Medical Products Agency mRNA - messenger ribonucleic acid MRSA - methicillin-resistant Staphylococus aureus MS - mass spectrometry NC - normal controls NF- Kb - nuclear factor kB NGG-I - normal animals administered with 5 gm% Glycyrrhiza glabra root powder vi NGG-II - normal animals administered with 10 gm% Glycyrrhiza glabra root powder NK - natural killer NLT- not less than NMDA - receptor- N-methyl D-aspartate receptor NMT- not more than NO - nitric oxide NOS - nitric oxide synthase OPC - oligomeric procyanidin OTC - over-the-counter OVA - ovalbumin PARP- poly (ADP-ribose) polymerase PB2 - post prandial 2h blood glucose levels PCA- passive cutaneous anaphylaxis PEL- primary effusion lymphoma PGE2 - prostaglandin E2 PI - phosphatidylinositol PI 3-kinases or PI3Ks - phosphoinositide 3-kinases PP - Portuguese pharmacopoeia PPAR - peroxisome proliferator-activated receptor RDDP - RNA-Dependent DNA-polymerase rhCK-II - recombinant human casein kinase II ROS - reactive oxygen species rRT - reverse transcriptase RT-PCR - reverse transcription-polymerase chain reaction SARS - severe acute respiratory syndrome SARS-CoV - SARS-associated coronavirus SBP - systolic blood pressure SDH - succinate dehydrogenase SHC- src-homology-collagen-like protein SLE - systemic lupus erythematosus SNMC - Stronger Neo-Minophagen C SOD - superoxide dismutase STZ - streptozotocin TBIL - total bilirubin TC - total cholesterol TCD - traditional Chinese drugs TCM - traditional Chinese medicine vii TG - triglycerides THM - traditional herbal medicine TNF-α - tumor necrosis factor alpha Total-C - total cholesterol TRLs - triglyceride -rich lipoproteins TST - tail suspension test TZD - thiazolidinediones USFDA - United States Food and Drug Administration VEGF - vascular endothelial growth factor VLDL - very low-density lipoprotein VSV - vesicular stomatitis vírus WBC - white blood cell count viii Index of Figures Figure 1 - Ephedra sinica…………………………………………………………………….....14 Figure 2 - Ephedra sinica………………………………………………………………….……15 Figure 3 - Ephedra major Host…………………………………………………………………15 Figure 4 - Ephedra distachya…………………………………………..………………………16 Figure 5 - Ephedra distachya…………………………………………………………………..16 Figure 6 - Pieces from Ephedra sinica……………………………………………………..…19 Figure 7 - Naturally occurring ephedra alkaloids……………………………………………..21 Figure 8 - Non-ephedrine alkaloids and amino compounds in ephedra species………. 22 Figure 9 - Miscellaneous non-alkaloidal natural constituents of ephedra species….…….22 Figure 10 - Chemical structures of the ephedra alkaloids.…………………….………..…..24 Figure 11 - Chemical structure of alloxan…………………………………………….……….27 Figure 12 - Example of ephedra containing products……………………………………..…42 Figure 13 - Example of ephedra containing products……………………………………..…43 Figure 14 - Example of ephedra containing products……………………………………..…43 Figure 15 - Example of ephedra containing products……………………………………..…43 Figure 16 - Example of ephedra containing products……………………………………..…43 Figure 17 - Prunus armeniaca Linne var. ansu Maxim. ………………………………….…54 Figure
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