by Lau Chun Hong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 179-195). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract in Chinese 摘要 --- p.iv / Acknowledgements --- p.vi / Table of Contents --- p.vii / List of Abbreviations --- p.xiii / List of Figures --- p.xvi / List of Tables --- p.xviii / Publications --- p.xix / Chapter Chapter1 --- Introduction --- p.1 / Chapter 1.1 --- Epidemiology of Diabetes Mellitus --- p.1 / Chapter 1.2 --- Definition of Diabetes Mellitus --- p.2 / Chapter 1.3 --- Glucose Homeostasis and Diabetes Mellitus --- p.2 / Chapter 1.4 --- Classification of Diabetes Mellitus --- p.5 / Chapter 1.4.1 --- Type 1 Diabetes Mellitus --- p.5 / Chapter 1.4.2 --- Type 2 Diabetes Mellitus --- p.6 / Chapter 1.4.3 --- Other Specific Types --- p.7 / Chapter 1.4.4 --- Gestational Diabetes --- p.9 / Chapter 1.4.5 --- Clinical Stages of Diabetes --- p.9 / Chapter 1.5 --- Diagnostic Criteria of Diabetes Mellitus --- p.10 / Chapter 1.6 --- Complications of Diabetes Mellitus --- p.12 / Chapter 1.7 --- Pharmacological Treatment of Diabetes --- p.13 / Chapter 1.7.1 --- Treatment of Type 1 Diabetes --- p.13 / Chapter 1.7.2 --- Treatment of Type 2 Diabetes --- p.14 / Chapter 1.7.2.1 --- Sulphonylureas --- p.17 / Chapter 1.7.2.2 --- Biguanides --- p.18 / Chapter 1.7.2.3 --- α-Glucosidase Inhibitors --- p.19 / Chapter 1.7.2.4 --- Thiazolidinediones --- p.20 / Chapter 1.8 --- Diabetes and Traditional Chinese Medicine --- p.21 / Chapter 1.9 --- Project Objective --- p.27 / Chapter Chapter2 --- Botanical and Phytochemical Studies --- p.28 / Chapter 2.1 --- Introduction --- p.28 / Chapter 2.2 --- Materials --- p.31 / Chapter 2.3 --- Authentication of Herbal Material --- p.41 / Chapter 2.3.1 --- Materials --- p.41 / Chapter 2.3.2 --- Phytochemical Studies --- p.43 / Chapter 2.3.2.1 --- Sample Preparation --- p.43 / Chapter 2.3.2.2 --- Thin Layer Chromatography --- p.46 / Chapter 2.3.3 --- Results --- p.51 / Chapter 2.4 --- Extraction of Herbal Material --- p.56 / Chapter 2.4.1 --- Materials and Methods --- p.56 / Chapter 2.4.2 --- Results --- p.46 / Chapter 2.5 --- Quantification of Sugar Content in Herbal Extracts --- p.58 / Chapter 2.5.1 --- Introduction --- p.58 / Chapter 2.5.2 --- Materials and Methods --- p.58 / Chapter 2.5.3 --- Results --- p.61 / Chapter 2.6 --- Discussion --- p.65 / Chapter Chapter3 --- In vitro Studies on Formula 2 and its Individual Herbs --- p.68 / Chapter 3.1 --- Introduction --- p.68 / Chapter 3.2 --- Intestinal Glucose Absorption Studies --- p.69 / Chapter 3.2.1 --- Introduction --- p.69 / Chapter 3.2.2 --- Materials and Methods --- p.70 / Chapter 3.2.2.1 --- Preparation of BBMV --- p.71 / Chapter 3.2.2.2 --- BBMV Glucose Uptake Assay --- p.72 / Chapter 3.2.2.3 --- Bicinchoninic Acid (BCA) Protein Assay --- p.73 / Chapter 3.2.2.4 --- Preparation of Herbal Chloroform Extract --- p.74 / Chapter 3.2.2.5 --- Glucose Uptake Assay with Herbal Extracts --- p.75 / Chapter 3.2.3 --- Results --- p.76 / Chapter 3.3 --- Hepatic Gluconeogenesis Studies --- p.79 / Chapter 3.3.1 --- Introduction --- p.79 / Chapter 3.3.2 --- Materials and Methods --- p.82 / Chapter 3.3.2.1 --- Cell Culture --- p.83 / Chapter 3.3.2.2 --- Glucose Production Assay --- p.83 / Chapter 3.3.2.3 --- PEPCK Assay --- p.85 / Chapter 3.3.3 --- Results --- p.86 / Chapter 3.4 --- Cellular Glucose Uptake Studies --- p.88 / Chapter 3.4.1 --- Introduction --- p.88 / Chapter 3.4.2 --- Materials and Methods --- p.89 / Chapter 3.4.2.1 --- Cell Culture --- p.89 / Chapter 3.4.2.2 --- Differentiation of 3T3-L1 --- p.90 / Chapter 3.4.2.3 --- 2-Deoxy-D-glucose Uptake Assay --- p.91 / Chapter 3.4.3 --- Results --- p.92 / Chapter 3.5 --- Discussion --- p.96 / Chapter 3.5.1 --- Intestinal Glucose Absorption Studies by BBMV --- p.96 / Chapter 3.5.2 --- Hepatic Gluconeogenesis Studies by H4IIE Cells --- p.97 / Chapter 3.5.3 --- Cellular Glucose Uptake Studies by Hs68 and 3T3-L1 Cells --- p.99 / Chapter 3.5.4 --- Conclusions --- p.100 / Chapter Chapter4 --- In vivo Studies on Selected Herbs --- p.103 / Chapter 4.1 --- Introduction --- p.103 / Chapter 4.1.1 --- Animal Models of Type 2 Diabetes --- p.103 / Chapter 4.1.2 --- Chemically-induced Diabetic Models --- p.104 / Chapter 4.1.3 --- Neonatal-STZ Diabetic Rats --- p.107 / Chapter 4.2 --- Basal Glycaemia Test --- p.109 / Chapter 4.2.1 --- Animals --- p.109 / Chapter 4.2.2 --- Testing Method --- p.110 / Chapter 4.2.3 --- Results --- p.112 / Chapter 4.3 --- Oral Glucose Tolerance Test --- p.114 / Chapter 4.3.1 --- Animals --- p.114 / Chapter 4.3.2 --- Testing Method --- p.114 / Chapter 4.3.3 --- Results --- p.116 / Chapter 4.4 --- Discussion --- p.119 / Chapter Chapter5 --- Bioassay-guided Fractionation of Cortex Moutan --- p.125 / Chapter 5.1 --- Introduction --- p.125 / Chapter 5.1.1 --- Phytochemical Studies of Cortex Moutan --- p.125 / Chapter 5.2 --- Organic Extraction of Cortex Moutan --- p.128 / Chapter 5.2.1 --- Extraction Method --- p.128 / Chapter 5.2.2 --- Results --- p.129 / Chapter 5.3 --- BBMV Glucose Uptake Assay with Fraction CM C --- p.131 / Chapter 5.3.1 --- Materials and Methods --- p.131 / Chapter 5.3.2 --- Results --- p.131 / Chapter 5.4 --- In vivo Studies of Fraction CM-C --- p.133 / Chapter 5.4.1 --- Materials and Methods --- p.133 / Chapter 5.4.2 --- Results --- p.133 / Chapter 5.5 --- Fractionation of Fraction CM-C --- p.137 / Chapter 5.5.1 --- Materials and Methods --- p.137 / Chapter 5.5.2 --- Results --- p.139 / Chapter 5.6 --- BBMV Glucose Uptake Assay with CM-C Sub-fractions --- p.142 / Chapter 5.6.1 --- Results --- p.142 / Chapter 5.7 --- Isolation of Active Compound in Fraction CM-C4 --- p.144 / Chapter 5.7.1 --- Materials and Methods --- p.145 / Chapter 5.7.2 --- Results --- p.146 / Chapter 5.8 --- Structure Elucidation of CM-C4a --- p.148 / Chapter 5.8.1 --- Materials and Methods --- p.148 / Chapter 5.8.2 --- Results --- p.149 / Chapter 5.9 --- Effect of Paeonol in Oral Glucose Tolerance Test --- p.152 / Chapter 5.9.1 --- Materials and Methods --- p.152 / Chapter 5.9.2 --- Results --- p.153 / Chapter 5.10 --- Discussion --- p.155 / Chapter Chapter6 --- General Discussion --- p.163 / Chapter 6.1 --- Introduction --- p.163 / Chapter 6.2 --- Summary of Research Findings --- p.164 / Chapter 6.3 --- Limitations and Improvements --- p.167 / Chapter 6.4 --- Future Directions --- p.169 / Chapter 6.5 --- Conclusion --- p.170 / Appendices --- p.172 / Appendix 1 Low Resolution EI Mass Spectrum of Paeonol Reference --- p.173 / Appendix 2 Low Resolution EI Mass Spectrum of CM-C4a --- p.174 / Appendix 3 High Resolution EI Mass Spectrum of Paeonol Reference --- p.175 / Appendix 4 High Resolution EI Mass Spectrum of CM-C4a --- p.176 / Appendix 5 1H-NMR Spectrum of Paeonol Reference --- p.177 / Appendix 6 1H-NMR Spectrum of CM-C4a --- p.178 / References --- p.179

Further mechanistic studies demonstrated that both Radix Rubiae and realgar were capable of inducing cellular apoptosis on HaCaT cells in a dose- and time-dependent manner as shown by morphological inspection, DNA fragmentation, TUNEL assay, cell cycle analysis, annexin V---PI staining and Western blot analysis. HPLC fingerprintings were constructed for quality control of the Radix Rubiae extract using mollugin as the chemical marker. Further phytochemical study found that ethyl acetate fraction of this herb possessed potent growth inhibition on HaCaT cells, with IC50 of 0.9 microg/ml. However, the chemical compounds obtained from commercial sources including mollugin, alizarin, purpurin, and quinizarin failed to induce growth inhibition. Meanwhile, arsenic trioxide, arsenic pentoxide and arsenic iodide, three arsenic salts presented in realgar, had significant anti-proliferative effect on HaCaT cells, with IC50 values of 2.4, 16 and 6.8 microM, respectively; and cellular apoptosis was found to be the underlying mechanism for the observed growth inhibitory activity. Furthermore, Radix Rubiae, realgar and arsenic compounds were also revealed to possess growth inhibition when evaluated in a PHA-activated PBMC model, and all of the substances except arsenic pentoxide significantly attenuated the release of inflammatory cytokines such as IFN-y, TNF-alpha and IL-2 in PBMC, indicating an anti-inflammatory effect. The in vivo mouse tail model experiments demonstrated that arsenic trioxide, arsenic pentoxide and arsenic iodide were able to markedly induce mouse tail keratinocyte differentiation, while such differentiation-modulating effect observed in the fraction of Radix Rubiae was only marginal. / In summary, Radix Rubiae and realgar extracts and three arsenic compounds have been identified and characterized as potential anti-psoriatic agents. The discoveries from the present PhD project not only help put the traditional use of these medicinal substances for psoriasis treatment on a scientific footing, but also open up new opportunities for their development into novel anti-psoriatic therapies. / Psoriasis, a chronic inflammatory skin disorder affecting approximately 2-3% of the population worldwide, is characterized histologically by hyperproliferation and aberrant differentiation of epidermal keratinocytes. Many conventional therapies are offered for psoriasis treatment but there exist problems such as unsatisfactory efficacy, side effects and drug resistance. Many patients therefore turn to alternative and complementary medicines for help. Traditionally, Chinese herbal medicine has been extensively used to treat psoriasis and produced promising clinical results. The present PhD study was conducted to investigate psoriasis-treating Chinese herbal medicines with an aim to identify effective anti-psoriatic agents. Sixty Chinese medicinal materials were selected for the screening project based on their ethnomedical use in psoriasis. The ethanolic extracts of these medicinal substances were evaluated for their anti-proliferative action on cultured HaCaT human keratinocytes using microplate SRB and MTT assays. Among them, the root of Rubia cordifolia L. (Radix Rubiae) and realgar were found to have significant anti-proliferative effects, with IC50 values of 1.4 and 6.6 microg/ml, respectively as measured by MTT assay, while they exerted mild significant cytotoxicity on the human fibroblast Hs-68 cell line. / Tse, Wai Pui. / Advisers: C. T. Che; Z. X. Lin. / Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: . / Thesis submitted in: October 2008. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 298-340). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Xing Hongtao. / "February 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 149-176). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Cao Hui. / Publication date from spine. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 180-194). / Acknowledgments --- p.v / Abstract --- p.vii / List of Tables --- p.xv / List of Figures --- p.xvii / Abbreviations and symbols --- p.xx / Chapter Chapter 1. --- General introduction / Chapter 1.1. --- Historical background --- p.1 / Chapter 1.2. --- Pharmacognostical development --- p.2 / Chapter 1.3. --- Importance of herb authentication --- p.3 / Chapter 1.4. --- Objective of study --- p.5 / Chapter Chapter 2. --- Literature review / Chapter 2.1. --- Botanical and taxonomic aspects --- p.9 / Chapter 2.1.1. --- Morphology --- p.9 / Chapter 2.1.2. --- Scientific names --- p.11 / Chapter 2.2. --- Chemical aspects --- p.13 / Chapter 2.3. --- Pharmacological aspects --- p.14 / Chapter 2.3.1. --- Antibacterial effect --- p.14 / Chapter 2.3.2. --- Antiphlogistic effect --- p.14 / Chapter 2.3.3. --- Antipyretic effect --- p.15 / Chapter 2.3.4. --- Effect in gastrointestinal propulsion --- p.15 / Chapter 2.3.5. --- Antineoplastic activity --- p.15 / Chapter 2.3.6. --- Hepatoprotective effect --- p.15 / Chapter 2.3.7. --- Inhibitory activity on enzymes --- p.17 / Chapter 2.3.8. --- Cardiovascular effect --- p.17 / Chapter 2.3.9. --- Acute toxicity (LD50) --- p.18 / Chapter 2.4. --- Pharmacognostical aspects --- p.18 / Chapter Chapter 3. --- Kudidan in Ben-cao literature / Chapter 3.1. --- Introduction --- p.23 / Chapter 3.2. --- Name evolution --- p.23 / Chapter 3.3. --- Natural distribution --- p.24 / Chapter 3.4. --- Characteristics --- p.25 / Chapter 3.5. --- Substitutions investigation --- p.26 / Chapter 3.6. --- Summary --- p.29 / Chapter Chapter 4. --- Morphological differences / Chapter 4.1. --- Plant identification --- p.36 / Chapter 4.1.1. --- Introduction --- p.36 / Chapter 4.1.2. --- Collection of voucher materials --- p.36 / Chapter 4.1.3. --- Plant morphology --- p.36 / Chapter 4.2. --- Macroscopical identification --- p.46 / Chapter 4.2.1. --- Introduction --- p.46 / Chapter 4.2.2. --- Materials and methods --- p.46 / Chapter 4.2.2.1. --- Commercial samples --- p.46 / Chapter 4.2.2.2. --- Macroscopical characteristics --- p.46 / Chapter 4.2.3. --- Results --- p.49 / Chapter Chapter 5. --- Histological identification / Chapter 5.1. --- Introduction --- p.58 / Chapter 5.2. --- Materials and methods --- p.59 / Chapter 5.2.1. --- Commercial samples --- p.59 / Chapter 5.2.1.1. --- Kudidan --- p.59 / Chapter 5.2.1.2. --- Pugongying --- p.59 / Chapter 5.2.1.3. --- Substitutes --- p.59 / Chapter 5.2.2. --- Authentic plant materials for comparison --- p.60 / Chapter 5.2.3. --- Methods --- p.60 / Chapter 5.2.3.1. --- Paraffin method --- p.60 / Chapter 5.2.3.2. --- Light microscopy --- p.62 / Chapter 5.2.3.3. --- Quantitative microscopy --- p.63 / Chapter 5.2.3.4. --- Scanning electron microscopy --- p.64 / Chapter 5.3. --- Results --- p.64 / Chapter 5.3.1. --- Microscopical characters of comparative plants --- p.64 / Chapter 5.3.2. --- Internal structures of herbs --- p.83 / Chapter 5.4. --- Discussion --- p.83 / Chapter Chapter 6. --- Chemical analysis / Chapter 6.1. --- Introduction --- p.99 / Chapter 6.2. --- Materials and methods --- p.100 / Chapter 6.2.1. --- Authentic samples --- p.100 / Chapter 6.2.2. --- Commercial samples --- p.100 / Chapter 6.2.3. --- Methods --- p.100 / Chapter 6.2.3.1. --- Isolation and characterization of standard substances --- p.100 / Chapter 6.2.3.2. --- Extraction of plant materials --- p.102 / Chapter 6.2.3.3. --- Thin layer chromatography --- p.102 / Chapter 6.3. --- Results and discussion --- p.104 / Chapter 6.3.1. --- TLC synopsis --- p.104 / Chapter 6.3.2. --- TLC analysis --- p.105 / Chapter 6.3.2.1. --- Qualitative evaluation of authentic plants --- p.105 / Chapter 6.3.2.2. --- Qualitative evaluation of commercial samples --- p.107 / Chapter 6.4. --- Summary --- p.107 / Chapter Chapter 7. --- Molecular fingerprinting / Chapter 7.1. --- Introduction --- p.115 / Chapter 7.2. --- Materials and methods --- p.120 / Chapter 7.2.1. --- Plant materials --- p.121 / Chapter 7.2.2. --- Herbal materials --- p.121 / Chapter 7.2.3. --- Total genomic DNA preparation --- p.121 / Chapter 7.2.3.1. --- CsCl/EtBr gradient method --- p.121 / Chapter 7.2.3.2. --- CTAB/CsCl gradient method --- p.123 / Chapter 7.2.3.3. --- CTAB miniprep method --- p.124 / Chapter 7.2.4. --- Qualitative analysis of genomic DNA --- p.125 / Chapter 7.2.5. --- Quantitative analysis of genomic DNA --- p.126 / Chapter 7.2.6. --- Genomic DNA fingerprinting --- p.126 / Chapter 7.2.6.1. --- DNA amplification --- p.126 / Chapter 7.2.6.1.1. --- AP-PCR --- p.127 / Chapter 7.2.1.1.2. --- RAPD --- p.128 / Chapter 7.2.6.2. --- Data analysis --- p.129 / Chapter 7.3. --- Results --- p.129 / Chapter 7.3.1. --- Studies on extraction of genomic DNA --- p.129 / Chapter 7.3.2. --- Genomic DNA fingerprinting by AP-PCR --- p.130 / Chapter 7.3.3. --- Genomic DNA fingerprinting by RAPD --- p.131 / Chapter 7.4. --- Discussion --- p.131 / Chapter 7.4.1. --- DNA extraction --- p.132 / Chapter 7.4.2. --- DNA fingerprinting of Kudidan --- p.136 / Chapter 7.4.3. --- Phylogenetic relationship between two genera Elephantopus and Pseudo-elephantopus of by DNA fingerprinting --- p.141 / Chapter Chapter 8. --- General summary and conclusion / Chapter 8.1. --- General summary --- p.165 / Chapter 8.1.1. --- Ben-cao investigation --- p.166 / Chapter 8.1.2. --- Investigation of commercial samples --- p.166 / Chapter 8.1.3. --- Histological characteristics --- p.167 / Chapter 8.1.4. --- Chemical analysis --- p.168 / Chapter 8.1.5. --- DNA fingerprinting --- p.168 / Chapter 8.2. --- Conclusion --- p.169 / Appendices / Chapter A) --- Solutions --- p.171 / Chapter B) --- Chinese characters cited in this Thesis --- p.173 / Chapter a) --- Herbal names --- p.173 / Chapter b) --- Book names --- p.175 / Chapter c) --- Personal names --- p.176 / Chapter d) --- Place names --- p.177 / Chapter e) --- Miscellaneous names --- p.179 / Bibliography --- p.180

Throughout the eighteenth century the majority of the population of Scotland were dependent on their own home remedies for treating illnesses. Early in the century doctors were scarce and the difficulties of travel plus the high fees they charged put their services beyond the reach of most people. Even later in the century when roads improved and an increasing number of medical graduates were trained, in rural Scotland domestic medicine was still the only form of treatment available to many. The sources of eighteenth century domestic remedies were largely the same as the sources of orthodox medicine, namely traditional herbal recipes derived from the ancients, and from the mediaeval herbals. Such remedies were perpetuated by word of mouth, in ballads and songs, and in diaries, letters and kitchen books, as well as in printed books. The present thesis aims to illustrate the type of home remedy used, drawing mainly on primary sources, and using as examples various common eighteenth century ailments, such as scurvy, smallpox, consumption, etc. Home remedies changed little in the course of the century, but orthodox medicine underwent considerable changes meanwhile, with the reform of the Pharmacopoeia and the so-called "rationalisation" of medicine. The result was that home and orthodox remedies diverged and many traditional herbal recipes were discarded by the orthodox medical men, some of which may have been of real therapeutic value. Contrary to expectations, it has been found that home remedies were often less complicated than their contemporary medical counterparts. An attempt has been made to identify botanically the numerous plants mentioned, and to give some indication, in the light of present pharmacological knowledge, of their possible therapeutic value. Future analyses may even show that some of the eighteenth century herbal remedies could prove of clinical value in the future.

Thesis (M.Pharm.)--University of the Witwatersrand, Faculty of Health Sciences, 2013. / Sexually transmitted infections (STIs) are a global concern and more specifically southern Africa has seen a tremendous upsurge in infection rates. KwaZulu-Natal is the province found to have the highest Human Immunodeficiency Virus and STI infection rates. From an ethnobotanical study conducted specifically in northern Maputaland (Mabibi, Tshongwe, Mseleni and Mbazwana), it was found that the lay people most often used plants in various combinations for the treatment of STI related symptoms. The use of these plant combinations were thus antimicrobially investigated and the toxicity properties determined. The dichloromethane: methanol (organic) and aqueous extracts were prepared for each plant in situ using collected ground dried plant material. The plants (individually and in combination) were investigated for toxic potential using the 3-[4,5-dimethyl-2-thiazol-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) cellular viability assay on the human kidney epithelial (Graham) cell line. The antimicrobial activities for each sample, as well as for each combination, were then further investigated using the minimum inhibitory concentration (MIC) assay. The six STI pathogens investigated in this study were Candida albicans (ATCC 10321), Ureaplasma urealyticum (clinical strain), Oligella ureolytica (ATCC 43534), Gardnerella vaginalis (ATCC 14018), Trichomonas vaginalis (clinical strain) and Neisseria gonnorhoeae (ATCC 19424).

by Suet-ching Leung. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 170-198.

by Wong Chun-kwok. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 233-246). / ABSTRACT --- p.I / ACKNOWLEDGEMENTS --- p.V / ABBREVIATIONS --- p.VI / PUBLICATIONS --- p.IX / CHAPTER / Chapter 1. --- GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- EFFECTOR CELLS MEDIATING ANTI一TUMOR IMMUNITY --- p.3 / Chapter 1.1.1 --- CYTOTOXIC T LYMPHOCYTES --- p.4 / Chapter 1.1.2 --- MACROPHAGES --- p.4 / Chapter 1.1.3 --- NATURAL KILLER CELLS --- p.5 / Chapter 1.1.4 --- LYMPHOKINE ACTIVATED KILLER CELLS --- p.7 / Chapter 1.1.5 --- TUMOR-INFILTRATING LYMPHOCYTES --- p.8 / Chapter 1.2 --- BIOLOGICAL RESPONSE MODIFIERS : THE NEW IMMUNOTHERAPY --- p.9 / Chapter 1. 3 --- CYTOKINES AS BIOLOGICAL RESPONSE MODIFIERS IN CANCER THERAPY --- p.12 / Chapter 1.3.1 --- INTERFERONS --- p.12 / Chapter 1.3.2 --- TUMOR NECROSIS FACTOR-ALPHA --- p.13 / Chapter 1.3.3 --- INTERLEUKIN-1 --- p.15 / Chapter 1.3.4 --- INTERLEUKIN-2 --- p.16 / Chapter 1.3.5 --- GRANULOCYTES /MACROPHAGES COLONY-STIMULATING FACTORS --- p.16 / Chapter 1.3.6 --- EPIDERMAL GROWTH FACTOR --- p.17 / Chapter 1.3.7 --- TRANSFORMING GROWTH FACTOR-BETA --- p.17 / Chapter 1.4 --- BIOACTIVE POLYSACCHARIDES FROM CHINESE MEDICINAL HERBS ACT AS BIOLOGICAL RESPONSE MODIFIERS --- p.18 / Chapter 2. --- AIM AND SCOPE OF INVESTIGATION --- p.27 / Chapter 3. --- MATERIALS AND METHODS --- p.30 / Chapter 3.1 --- MATERIALS --- p.30 / Chapter 3.2 --- METHODS --- p.39 / Chapter (I) --- "EXTRACTION, FRACTIONATION AND CHARACTERIZATION OF PSEUDOSTELLARIA HETEROPHYLLA" / Chapter 3.2.1 --- Hot water extraction and stepwise alcohol precipitation --- p.39 / Chapter 3.2.2 --- "Determination of carbohydrate, protein, uronic acid contents" --- p.41 / Chapter 3.2.3 --- Gel filtration --- p.41 / Chapter 3.2.4 --- Anion-exchange chromatography --- p.41 / Chapter 3.2.5 --- Paper chromatography --- p.42 / Chapter 3.2.6 --- Gas liquid chromatography --- p.43 / Chapter 3.2.7 --- Determination of molecular weight by high performance liquid chromatography --- p.44 / Chapter 3.2.8 --- SDS-polyacrylamide gel electrophoresis --- p.44 / Chapter 3.2.9 --- Determination of the bio´ؤtoxicity of samples --- p.46 / Chapter 3.2.10 --- Treatment of samples with sodium periodate or acetic acid --- p.46 / Chapter (II) --- ASSAYS OF IMMUNOMODULATORY ACTIVITIES OF PSEUDOSTELLARIA HETEROPHYLLA ON LYMPHOCYTES / Chapter 3.2.11 --- Isolation and preparation of cells --- p.48 / Chapter 3.2.12 --- In vitro lymphocyte transformation assay --- p.50 / Chapter 3.2.13 --- Mixed lymphocyte culture --- p.50 / Chapter 3.2.14 --- Depleting mouse T cells by anti-Thy-1.2 antibody plus complement treatment --- p.51 / Chapter 3.2.15 --- Depleting mouse B cells by anti-mouse B cell antibody plus complement treatment --- p.51 / Chapter 3.2.16 --- Haemolytic plaque assay --- p.52 / Chapter 3.2.17 --- Delayed-type hypersensitivity --- p.53 / Chapter 3.2.18 --- Immunofluorescent assay for interleukin-2 receptor expression --- p.54 / Chapter 3.2.19 --- Assay of murine interleukin-2 --- p.55 / Chapter (III) --- ASSAYS OF IMMUNOMODULATORY ACTIVITIES OF PSEUDOSTELLARIA HETEROPHYLLA ON MACROPHAGES / Chapter 3.2.20 --- Assay of murine interleukin-1 --- p.55 / Chapter 3.2.21 --- In vivo migration of macrophages --- p.56 / Chapter 3.2.22. --- Assay of phagocytic activity of peritoneal macrophages --- p.56 / Chapter 3.2.23 --- Northern blotting of mRNA of β-actin gene extracted from peritoneal exudate cells --- p.57 / Chapter (IV) --- ASSAYS OF ANTI-TUMOR ACTIVITIES OF PSEUDOSTELLARIA HETEROPHYLLA / Chapter 3.2.24 --- Assay of anti-tumor activity in vitro --- p.62 / Chapter 3.2.25 --- Assay of anti-tumor activity in vivo --- p.63 / Chapter 3.2.26 --- Priming effect of different fractions for the induction of TNF-α in mice --- p.63 / Chapter 3 .2.27 --- In vitro stimulation of TNF-α release from resting peritoneal macrophages --- p.64 / Chapter 3.2.28 --- Effects of P. heterophylla polysaccharides on TNF-α and IFN-gamma production as well as EAT growth in vivo --- p.64 / Chapter 3.2.29 --- Macrophage-mediated cytostatic activity --- p.65 / Chapter 3 2.30 --- Assay of lymphokine-activated killer cell activity --- p.66 / Chapter 3 2.31 --- Assay of natural killer cell activity --- p.67 / Chapter 3.2.32 --- Assay of tumor-infiltrating lymphocytes --- p.68 / Chapter (V) --- ASSAYS FOR THE EFFECTS OF PSEUDOSTELLARIA HETEROPHYLLA ON THE PROLIFERATION AND DIFFERENTIATION OF MURINE BONE MARROW CELLS AND MYELOID LEUKAEMIC Ml CELLS / Chapter 3.2.33 --- Assay of proliferation of murine bone marrow cells --- p.69 / Chapter 3.2.34 --- Assay of differentiation of murine bone marrow cells --- p.70 / Chapter 3.2.35 --- Assay of differentiation of Ml cells --- p.71 / Chapter 3.2.36 --- Induction of GM-CSF from bone marrow cells and Ml cells --- p.71 / Chapter (VI) --- ASSAYS OF THE IMMUNORESTORATIVE PROPERTIES OF PSEUDOSTELLARIA HETEROPHYLLA / Chapter 3.2.37 --- Immunorestoration in tumor-bearing mice --- p.72 / Chapter 3.2.38 --- Immunorestoration in aged mice --- p.72 / Chapter 3.2.39 --- Immunorestoration in cyclophosphamide- treated mice --- p.73 / Chapter 3.2.40 --- Statistical analysis --- p.73 / Chapter 4. --- "EXTRACTION, FRACTIONATION AND CHARACTERIZATION OF MITOGENIC FRACTIONS FROM PSEUDOSTELLARIA HETEROPHYLLA" / INTRODUCTION --- p.74 / RESULTS --- p.76 / Chapter 4.1 --- Extraction and fractionation of Pseudostellaria heterophylla --- p.76 / Chapter 4.2 --- Gel filtration and anion-exchange chromatography --- p.76 / Chapter 4.3 --- Characterization of bioactive fractions from Pseudostellaria heterophylla --- p.79 / Chapter 4.4 --- Mitogenic activity of fraction PH-I on murine lymphocytes in vitro --- p.96 / Chapter 4.5 --- Mitogenic effect of PH-I on murine lymphocytes in vivo --- p.102 / Chapter 4.6 --- Effect of PH-I on polyclonal B cell activation --- p.102 / Chapter 4.7 --- Adjuvant effect of PH-I on antibody response to SRBC in vivo --- p.106 / Chapter 4.8 --- Evidences to support the mitogenic activity of PH-I is due to its polysaccharide rather than due to the contamination by LPS --- p.106 / Chapter 4.9 --- The effects of PH-I on IL-2 production and IL-2 receptor expression on murine lymphocytes in vitro --- p.110 / Chapter 4.10 --- The mitogenic activity of the purified fractions on murine lymphocytes in vitro --- p.110 / Chapter 4.11 --- Adjuvant effect of PH-I Ab on antibody response to SRBC in vivo --- p.116 / Chapter 4.12 --- Mitogenic effect of PH-I C on murine lymphocytes in vivo --- p.116 / Chapter 4.13 --- Evidences to support the mitogenic activity of PH-I Ab is due to its polysaccharide rather than due to the contamination by LPS --- p.122 / DISCUSSION --- p.122 / Chapter 5. --- IMMUNOMODULATING AND ANTI-TUMOR ACTIVITIES OF ALCOHOL- INSOLUBLE FRACTION (PH-I) FROM THE HOT WATER EXTRACT OF PSEUDOSTELLARIA HETEROPHYLLA / INTRODUCTION --- p.133 / RESULTS --- p.135 / Chapter 5.1 --- Effect of PH-I on cytokine production --- p.135 / Chapter 5.2 --- In vivo activation of macrophages by PH-I --- p.135 / Chapter 5.3 --- Effect of PH-I on the activation of β-actin gene transcription in peritoneal macrophages --- p.142 / Chapter 5.4 --- Effect of PH-I on the in vitro growth of various tumor cell lines --- p.142 / Chapter 5.5 --- Immunorestoration of PH-I on the mitogenic response in EAT-bearing mice --- p.147 / DISCUSSION --- p.147 / Chapter 6. --- IMMUNOMODULATING AND ANTI-TUMOR ACTIVITIES OF PURIFIED FRACTIONS SEPARATED FROM PSEUDOSTELLARIA HETEROPHYLLA / INTRODUCTION --- p.154 / RESULTS --- p.157 / Chapter 6.1 --- In vitro anti-tumor activities of P. heterophylla --- p.157 / Chapter 6.2 --- In vivo anti-tumor activities of P. heterophylla --- p.165 / Chapter 6.3 --- Effect of P. heterophylla fractions on induction of delayed-type hypersensitivity --- p.165 / Chapter 6.4 --- Effect of PH-I fraction on the cytotoxic alloreactive T lymphocytes in vitro --- p.165 / Chapter 6.5 --- Effect of P. heterophylla on the production of TNF-α and IFN-gamma --- p.170 / Chapter 6.6 --- Effect of P. heterophylla on the activation of macrophages --- p.176 / Chapter 6.7 --- "Effect of P. heterophylla on the activation of NK, LAK and TIL" --- p.181 / Chapter 6.8 --- The effect of combined treatment of EAT-bearing mice with P. heterophylla amd Mur-TNF-α on the growth of EAT cells in vivo --- p.181 / Chapter 6 9 --- Immunorestorative activities of P. heterophylla in aged mice and cyclophosphamide-treated mice --- p.187 / DISCUSSION --- p.187 / Chapter 7. --- EFFECTS OF PSEUDOSTELLARIA HETEROPHYLLA ON PROLIFERATION AND DIFFERENTIATION OF MURINE BONE MARROW CELLS AND MYELOID LEUKAEMIC Ml CELLS / INTRODUCTION --- p.200 / RESULTS --- p.202 / Chapter 7.1 --- Effect of P. het erophyl1a on the proliferation and differentiation of murine bone marrow cells --- p.202 / Chapter 7 .2 --- Effects of P. heterophyl la on the proliferation and differentiation of murine myeloid leukaemia Ml cells --- p.205 / Chapter 7 .3 --- Effects of P. heterophylla on GM-CSF production by bone marow cells and myeloid leukaemia Ml cells --- p.214 / DISCUSSION --- p.218 / Chapter 8. --- CONCLUSIONS AND FUTURE PERSPECTIVES --- p.223 / BIBLIOGRAPHY --- p.233

Bioactivity-guided isolation of SFE oil led to the identification of another sesquiterpene lactone, 6-O-angeloylprenolin, containing the bioactive alpha, beta-unsaturated cyclopentenone. MTT results showed that CNE cells were more susceptible to 6-O-angeloylenolin than the normal Hs68 cells. Besides, the inhibitory effect of 6-O -angeloylenolin on the CNE cells was slightly stronger than that of cisplatin, the positive control, albeit statistical insignificance. / Both volatile oils prepared by supercritical fluid extraction (SFE) and steam distillation (SD) were evaluated for their anti-NPC potential. Results showed that SFE oil was much stronger than that of SD oil. SFE oil significantly inhibited the growth of CNE cells by dysfunctioning the mitochondria and activating caspases. Gas chromatography-mass spectrometry analysis revealed that the responsible principals in the SFE oil were likely homologues of sesquiterpene lactones. / Centipeda minima (L.) A. Br. (Compositae), a Chinese medicinal herb, is used to treat nasopharyngeal carcinoma (NPC) in the Chinese folk. However, there is a paucity of information on its anticancer activities. In particular, both of its anti-NPC potential and the potent constituents remain elusive. / In this study, the n-hexane fraction of C. minima showed broad spectrum of inhibitory effects on five human cancer cell lines, including the breast carcinoma MCF7 cells, the prostate carcinoma PC-3 cells, the hepatocellular carcinoma Hep G2 cells, the nasopharyngeal cancer CNE cells and the acute promyelocytic leukemia HL-60 cells, with IC 50 values ranging from 6.1 to 47.3 mug/mL. Bioactivity-guided separation of the n-hexane fraction using the CNE cells as the cellular system led to the isolation of a sesquiterpene lactone, 2beta-(isobutyryloxy)florilenalin (IF), which contained the bioactive alpha-methylene-gamma-lactone ring. IF significantly induced CNE cell death with an IC50 value of 3.1 mug/mL. Despite this potency, its effect on the normal Hs68 cells was much weaker, with an IC50 value larger than 50 mug/mL. Its inhibitory effect on the CNE cells ascribed to apoptotic induction as evidenced by the cumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage. Mechanistic study showed that both extrinsic and intrinsic apoptotic pathways were activated. In the extrinsic pathway, IF activated caspase-8, which further induced the activation of caspase-3 and caspase-7. In the intrinsic pathway, IF regulated the expressions of Bcl-2 family proteins, followed by depletion of mitochondrial membrane potential (Delta&PSgr;m), the release of cytochrome c to cytosol, the activation of caspase-9 and other downstream caspases, and finally the induction of apoptosis. / Mechanistic investigation showed that 6-O-angeloylenolin caused cell cycle arrest at S and G2/M phases and induced apoptosis in CNE cells. For the cell cycle arrest, a sharp decrease was found in the expressions of cyclin D1, cyclin D3, cdc25c, and p-cdc25c, with concomitant decrease in CDK4, cyclin A, cyclin E, p-Rb(Ser780), p21Waf1/Cip1, cdc2 and p-cdc2. For the induction of apoptosis, externalization of phosphatidylserine and depletion of Delta&PSgr;m prior to the detection of sub-G1 peak were found. Other apoptotic features including the presence of apoptotic bodies, the activation of caspase-3 activity and the cleavage of PARP were observed. Activation of caspase-8 and caspase-10 was detected. Besides, 6-O -angeloylenolin induced the release of cytochrome c and AIF to cytosol. The former formed apoptosome with caspase-9, further activated the downstream caspase-3 and caspase-7 and cleaved PARP, while the latter was translocated into the nucleus and caused large-scale DNA fragmentation. Failure of the pan-caspase inhibitor, z-VAD-fmk, to interrupt the apoptotic induction by 6-O-angeloylenolin suggested that caspase-independent pathway was involved. 6-O-Angeloylenolin was able to activate Akt, ERK and JNK pathways. But only with the addition of JNK inhibitor (SP600125), significant suppression of the 6-O-angeloylenolin-induced apoptosis was observed, suggesting the involvement of the JNK pathway in the apoptotic pathway. Taken together, this study provided a better mechanistic insight into the potential application of 6-O-angeloylenolin as a candidate for NPC treatment. / Overall, this study revealed that two sesquiterpene lactones, including IF and 6-O-angeloylenolin were found to be responsible for the potent anti-NPC effect of C. minima. This study reiterates the notion that Chinese medicinal herbs traditionally applied to cancer treatment may be good sources of anticancer drug discovery, and sesquiterpene lactone may be a group of noteworthy lead compounds displaying anti-NPC potential. / Su, Miaoxian. / Adviser: Hau Yin Chung. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 100-113). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

by Lam Tin Lun. / "July, 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 308-327). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.