Chan Yin Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 147-167). / Abstracts in English and Chinese. / ABSTRACT --- p.III / ACKNOWLEDGEMENT --- p.X / TABLE OF CONTENTS --- p.XI / ABBREVIATIONS --- p.XV / LIST OF FIGURES --- p.XVII / LIST OF TABLES --- p.XXI / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Introduction to Cardiovascular Disease and Atherosclerosis --- p.1 / Chapter 1.1.1 --- Cardiovascular Disease --- p.1 / Chapter 1.1.2 --- A therosclerosis --- p.3 / Chapter 1.1.2.1 --- Structure of Arteries --- p.4 / Chapter 1.1.2.2 --- Pathophysiology of Atherosclerosis --- p.5 / Chapter 1.1.2.3 --- Endothelial Dysfunction --- p.8 / Chapter 1.1.3 --- Current Western Therapies --- p.11 / Chapter 1.1.3.1 --- Surgery --- p.11 / Chapter 1.1.3.2 --- Western Medications --- p.13 / Chapter 1.1.4 --- Traditional Chinese Medicine --- p.17 / Chapter 1.1.4.1 --- Long History --- p.17 / Chapter 1.1.4.2 --- As Alternative Medicine --- p.18 / Chapter 1.1.4.3 --- Modernization of Chinese Medicine --- p.19 / Chapter 1.2 --- Introduction and Selection of Chinese Medicine --- p.20 / Chapter 1.2.1 --- Selection ofTCM Formulation from Pharmacopoeia --- p.20 / Chapter 1.2.1.1 --- Compound Formulation --- p.20 / Chapter 1.2.2 --- Introduction to the Herbal Medicines --- p.21 / Chapter 1.2.2.1 --- Danshen (Salvia miltiorrhiza) --- p.21 / Chapter 1.2.2.2 --- Gegen (Puerariae thomsonii and Puerariae lobata) --- p.22 / Chapter 1.2.2.3 --- Yanhu (Corydalis yanhusuo) and its Exclusion --- p.24 / Chapter 1.2.3 --- Source and Authentication of the Herbal Medicines --- p.25 / Chapter CHAPTER 2 --- OPTIMIZATION OF DANSHEN-GEGEN FORMULA --- p.26 / Chapter 2.1 --- Project History --- p.26 / Chapter 2.2 --- aims for the present study --- p.27 / Chapter 2.3 --- Methods and Materials --- p.30 / Chapter 2.3.1 --- Extracts --- p.30 / Chapter 2.3.2 --- Extraction Process --- p.31 / Chapter 2.3.3 --- In vitro Antioxidation Model --- p.33 / Chapter 2.3.4 --- Ex vivo Vasodilation Model --- p.35 / Chapter 2.3.5 --- Statistical Analysis --- p.38 / Chapter 2.4 --- Results --- p.39 / Chapter 2.4.1 --- Vasodilation Results --- p.39 / Chapter 2.4.2 --- Antioxidation Results --- p.43 / Chapter 2.5 --- Discussion --- p.46 / Chapter 2.6 --- Further Modification of the Formula --- p.49 / Chapter 2.6.1 --- Extracts --- p.49 / Chapter 2.6.2 --- Results --- p.49 / Chapter 2.7 --- discussion --- p.52 / Chapter CHAPTER 3 --- MARKER CHEMICAL CONTENTS OF HERBAL EXTRACTS AND THEIR PHARMACOLOGICAL PROPERTIES --- p.56 / Chapter 3.1 --- HPLC Analysis of Marker Contents --- p.56 / Chapter 3.1.1 --- Methods --- p.57 / Chapter 3.1.2 --- Results --- p.58 / Chapter 3.1.2.1 --- HPLC Chromatograms --- p.59 / Chapter 3.1.2.2 --- Content Percentage of Marker Compounds --- p.63 / Chapter 3.1.3 --- Discussion --- p.64 / Chapter 3.2 --- Studies on Marker Compounds --- p.65 / Chapter 3.2.1 --- Introduction --- p.65 / Chapter 3.2.2 --- Methods and Materials --- p.67 / Chapter 3.2.2.1 --- Source of Pure Compounds --- p.67 / Chapter 3.2.2.2 --- Purification and Identification of SAB --- p.68 / Chapter 3.2.2.3 --- Vasodilation model --- p.70 / Chapter 3.2.2.4 --- Antioxidation Model --- p.71 / Chapter 3.2.2.5 --- Structures of Pure Compounds --- p.72 / Chapter 3.2.3 --- Results --- p.73 / Chapter 3.2.3.1 --- Vasodilation Results --- p.73 / Chapter 3.2.3.2 --- Antioxidation Results --- p.76 / Chapter 3.3 --- Discussion --- p.79 / Chapter 3.4 --- Synergistic Effect Study --- p.85 / Chapter 3.4.1 --- Introduction --- p.85 / Chapter 3.4.2 --- Methods --- p.85 / Chapter 3.4.3 --- Results --- p.86 / Chapter 3.4.4 --- Discussion --- p.88 / Chapter 3.5 --- STUDY ON 3'-HYDROXYPlIERARIN AND 3'-METHOXYPUERARIN PURIFIED FROM YFGE --- p.90 / Chapter 3.5.1 --- 3 '-hydroxypuerarin and 3'-methoxypuerarin --- p.90 / Chapter 3.5.2 --- Methods and Materials --- p.91 / Chapter 3.5.2.1 --- Purification by HPLC semi-preparation --- p.91 / Chapter 3.5.2.2 --- Bioassays --- p.93 / Chapter 3.5.3 --- Results --- p.94 / Chapter 3.5.3.1 --- Vasodilation Study --- p.94 / Chapter 3.5.3.2 --- Antioxidative Effect of Yege --- p.95 / Chapter 3.5.4 --- Discussion / Chapter CHAPTER 4 --- MECHANISTIC STUDY --- p.98 / Chapter 4.1 --- Introduction --- p.98 / Chapter 4.1.1 --- Nitric Oxide-mediated Vasodilation --- p.99 / Chapter 4.1.2 --- Prostacyclin-mediated Vasodilation --- p.100 / Chapter 4.1.3 --- EDHF-mediated Vasodilation --- p.101 / Chapter 4.1.4 --- Endothelium-dependent and -independent Vasodilations --- p.103 / Chapter 4.2 --- Methods and Materials --- p.104 / Chapter 4.3 --- Results --- p.107 / Chapter 4.3.1 --- Danshen-Gegen Formula (DY80) --- p.107 / Chapter 4.3.2 --- Salvianolic acid B --- p.112 / Chapter 4.3.3 --- Daidzein --- p.117 / Chapter 4.4 --- Discussion --- p.121 / Chapter CHAPTER 5 --- STUDY ON LIPID PEROXIDATION AND UPTAKE BY MACROPHAGES --- p.128 / Chapter 5.1 --- Study of DY 80 and SAB on Copper-ion induced Low Density Lipoprotein Oxidation --- p.128 / Chapter 5.1.1 --- Pathologic Role of oxidized Low Density Lipoprotein --- p.128 / Chapter 5.1.2 --- Antioxidants in Low Density Lipoprotein and Role of Transition Metals --- p.129 / Chapter 5.1.3 --- Methods and Materials --- p.130 / Chapter 5.1.4 --- Results --- p.131 / Chapter 5.1.5 --- Discussion --- p.133 / Chapter 5.2 --- Study of Scavenger Receptor Regulation in Macrophages --- p.135 / Chapter 5.2.1 --- Introduction --- p.135 / Chapter 5.2.2 --- Methods and Materials --- p.136 / Chapter 5.2.3 --- Results --- p.139 / Chapter 5.2.4 --- Discussions --- p.140 / Chapter CHAPTER 6 --- General Discussion --- p.143 / REFERENCES --- p.147

Choi Wai-wah. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 120-138). / Abstracts in English and Chinese. / Statement --- p.i / Acknowledgements --- p.ii / Abstract --- p.iii / Abstract (Chinese Version) --- p.v / Table of Contents --- p.vii / List of Tables --- p.xii / List of Figures --- p.xiii / List of Abbreviations --- p.xv / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- "Hemoglobin ´ؤ Structures, Types and Functions" --- p.1 / Chapter 1.1.1 --- Structures of Hemoglobin --- p.1 / Chapter 1.1.2 --- Types of Hemoglobin --- p.2 / Chapter 1.1.3 --- Functions of Hemoglobin --- p.3 / Chapter 1.2 --- Human Globin Genes and Their Regulation --- p.5 / Chapter 1.2.1 --- Organization of the Human Globin Genes --- p.5 / Chapter 1.2.2 --- Regulation of Globin Gene Expression --- p.6 / Chapter 1.2.2.1 --- The Locus Control Region (LCR) --- p.6 / Chapter 1.2.2.2 --- Cis-Regulatory Elements --- p.7 / Chapter 1.2.2.2.1 --- Promoters --- p.7 / Chapter 1.2.2.2.2 --- Enhancers --- p.7 / Chapter 1.2.2.2.3 --- Silencers --- p.8 / Chapter 1.2.2.3 --- Trans-Acting Factors --- p.8 / Chapter 1.2.2.3.1 --- GATA Family --- p.9 / Chapter 1.2.2.3.2 --- Kruppel-like Factors --- p.9 / Chapter 1.2.2.3.3 --- Nuclear Factor-Erythroid (NF-E) --- p.9 / Chapter 1.2.2.4 --- Chromatin Remodelling --- p.10 / Chapter 1.2.2.5 --- Intergenic Sequences --- p.11 / Chapter 1.3 --- Mechanisms of Hemoglobin Switching --- p.12 / Chapter 1.3.1 --- Autonomous Silencing --- p.12 / Chapter 1.3.2 --- LCR and Globin Gene Interaction --- p.12 / Chapter 1.4 --- Hemoglobinopathies --- p.14 / Chapter 1.4.1 --- α -thalassemia --- p.14 / Chapter 1.4.2 --- β -thalassemia --- p.14 / Chapter 1.4.3 --- Sickle Cell Anemia --- p.16 / Chapter 1.5 --- Therapies for β-thalassemia --- p.16 / Chapter 1.5.1 --- Blood Transfusion --- p.16 / Chapter 1.5.2 --- Bone Marrow Transplantation --- p.17 / Chapter 1.5.3. --- Gene Therapy --- p.17 / Chapter 1.6 --- Gene Switch Therapy --- p.18 / Chapter "1.6,1" --- Pharmacological Induction of HbF --- p.18 / Chapter 1.6.1.1 --- Hydroxyurea --- p.19 / Chapter 1.6.1.2 --- Butyrate --- p.20 / Chapter 1.6.1.3 --- Summary --- p.21 / Chapter 1.7 --- Objectives --- p.22 / Chapter Chapter 2 --- Induction of HbF by LC978 in K562 / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- Materials --- p.26 / Chapter 2.2.1 --- Chemicals and Reagents --- p.26 / Chapter 2.2.2 --- Kits --- p.27 / Chapter 2.2.3 --- Buffers and Solutions --- p.27 / Chapter 2.2.4 --- Primers --- p.30 / Chapter 2.2.5 --- Equipment and Other Consumables --- p.30 / Chapter 2.2.6 --- Maintenance of K562 --- p.31 / Chapter 2.2.7 --- Handling and Treatment of utilities for RNA isolation --- p.31 / Chapter 2.3 --- Methods --- p.32 / Chapter 2.3.1 --- Dose-response and time-response study of LC978 in K562 by TMB assay --- p.32 / Chapter 2.3.2 --- Detection of γ -Globin Gene Expression in LC978-induced K562 by RT-PCR --- p.33 / Chapter 2.3.3 --- Fetal Hemoglobin Analysis by Human Fetal Hemoglobin (HbF) ELISA Quantitation Kit --- p.36 / Chapter 2.3.4 --- Statistical Analysis --- p.38 / Chapter 2.4 --- Results --- p.39 / Chapter 2.4.1 --- Dose-response and time-response study of LC978 in K562 by TMB assay --- p.39 / Chapter 2.4.2 --- Detection of γ -Globin Gene Expression in LC978-induced K562 by RT-PCR --- p.45 / Chapter 2.4.3 --- Fetal Hemoglobin Analysis by Human Fetal Hemoglobin (HbF) ELISA Quantitation Kit --- p.48 / Chapter 2.5 --- Discussions --- p.51 / Chapter Chapter 3 --- Signal Transduction Pathways Modulated by LC978 / Chapter 3.1 --- Introduction --- p.54 / Chapter 3.2 --- Materials --- p.57 / Chapter 3.2.1 --- Chemicals and Reagents --- p.57 / Chapter 3.2.2 --- Kits --- p.57 / Chapter 3.2.3 --- Buffers and Solutions --- p.58 / Chapter 3.2.4 --- Primers --- p.59 / Chapter 3.2.5 --- Equipment and Other Consumables --- p.60 / Chapter 3.2.6 --- Maintenance of K562 --- p.60 / Chapter 3.2.7 --- Handling and Treatment of utilities for RNA isolation --- p.60 / Chapter 3.3 --- Methods --- p.61 / Chapter 3.3.1 --- Identification of Signaling Pathways by Microarray --- p.61 / Chapter 3.3.2 --- Real-time RT-PCR --- p.65 / Chapter 3.4 --- Results --- p.67 / Chapter 3.4.1 --- Identification of Signaling Pathways by Microarray --- p.67 / Chapter 3.4.2 --- Real-time RT-PCR --- p.74 / Chapter 3.5 --- Discussions --- p.80 / Chapter Chapter 4 --- MAPK pathways and HbF induction by LC978 / Chapter 4.1 --- Introduction --- p.84 / Chapter 4.2 --- Materials --- p.87 / Chapter 4.2.1 --- Chemicals and Reagents --- p.87 / Chapter 4.2.2 --- Kits --- p.88 / Chapter 4.2.3 --- Buffers and Solutions --- p.88 / Chapter 4.2.4 --- Equipment and Other Consumables --- p.90 / Chapter 4.2.5 --- Maintenance of K562 --- p.90 / Chapter 4.3 --- Methods --- p.91 / Chapter 4.3.1 --- "Roles of three MAPKs ´ؤ ERK, JNK and p38 in LC978-mediated γ -globin gene induction in K562 using CASE´ёØ Kits" --- p.91 / Chapter 4.3.2 --- Effect of p38 inhibitor SB203580 on HbF induction --- p.94 / Chapter 4.3.3 --- Statistical Analysis --- p.97 / Chapter 4.4 --- Results --- p.98 / Chapter 4.4.1 --- "Roles of three MAPKs - ERK, JNK and p38 in LC978-mediated γ -globin gene induction in K562 using CASETM Kits" --- p.98 / Chapter 4.4.2 --- Effect of p38 inhibitor SB203580 on HbF induction --- p.106 / Chapter 4.5 --- Discussions --- p.110 / Chapter Chapter 5 --- Summary and Prospects / Appendix / References

全球過敏性疾病的患病率逐漸增加。大約30 - 40的世界人口患有一個或多個過敏性疾病，它絶對是一個國際性的公共健康問題。在過去三十年，過敏性皮膚炎的發病率增加了2-3 倍，當中患病率最高的是嬰兒和兒童，而且現時並沒有明確的治療方法。然而，對過敏性疾病有效的治療方法仍然缺乏，大多數傳統的治療涉及臨床改善，但不針對促進過敏性炎症發病機制中的主要因素。這些傳統的治療方法都有不良副作用。因此，發展一個更安全和非類固醇的治療方式成為了新的趨勢。 / 從過往的臨床試驗中，患有中度至嚴重過敏性皮膚炎的兒童服用由五種中藥制成的Pentaherbs（PHF）膠囊藥丸後， 顯著地改善他們的生活質數，降低了過敏性皮膚炎指數（SCORAD）及減少使用傳統藥物類固醇的份量，更沒有出現任何不良藥物作用。實驗結果指出PHF 有潛力替代類固醇，成為治療過敏性皮膚炎的取代品。在本研究中，我們使用炎症相關的細胞因子IL-33，激活在有或沒有與皮膚成纖維細胞一起培植下的嗜鹼性細胞系KU812 細胞， 來探討了PHF，牡丹皮（DP，PHF 的五種草藥之一）和沒食子酸（GA，牡丹皮的主要成分之一）的抗炎和抗過敏特性。 / 在過敏性炎症中，嗜鹼性粒細胞是一個重要的效應細胞。我們利用細胞因子IL-33 激活嗜鹼性粒細胞系KU812 細胞，並從研究結果發現出PHF，DP 和GA 能有效及顯著地抑制細胞間粘附分子ICAM-1 的表達，炎症相關趨化因子CCL2，CCL5，CXCL8 和促炎細胞因子IL-6 的釋放。這證實出PHF, DP 和GA有抗炎和抗過敏的特性。在進一步的研究中，我們加入一種常用醫治過敏性炎症藥物的合成類固醇地塞米松, 與PHF, DP 和GA 結合使用。從各種組合的不同濃度地塞米松與PHF，DP 和GA 中，我們發現聯合使用低濃度為0.01 微克/毫升的地塞米松和10 微克/毫升GA 可進一步抑制ICAM-1 在KU812 的表達，趨化因子CCL2 和CCL5 釋放。此外，沒食子酸可顯著抑制細胞內信號分子p38 絲裂原活化蛋白激酶 (MAPK)，IκB-α和JNK 的表達。這表明了黏附分子的表達，趨化因子和細胞因子的釋放的抑製是經由p38 MAPK，IκB-α和JNK 訊息傳遞路徑所調節。實驗證實PHF，DP 和GA 具有抗炎和抗過敏的特性，與過往的臨床試驗結果一致。 / 為了更進一步研究沒食子酸和地塞米松在過敏性炎症的發病機制中扮演的角色， 我們建立了一個體外的模仿患者皮膚皮炎症的模型，共同培養嗜鹼性細系KU812 細胞和皮膚成纖維細胞 。我們發現，單沒食子酸的應用已經可以顯著地抑制在KU812 細胞和成纖維細胞表面粘附分子的表達，並減低釋放過敏性炎症相關的趨化因子CCL2，CCL5，CXCL8 和促炎細胞因子IL-6。此外，地塞米松和沒食子酸的結合使用能增強抑制KU812 細胞面上ICAM-1 的表達，和皮膚成纖維細胞面上ICAM-1 和VCAM-1 的表達，與及趨化因子CCL2 和CXCL8，促炎性細胞因子IL-6 的釋放。 / 上述調查結果表明，天然植物產品PHF，DP 和GA 是具有消炎和抗過敏的作用，抑制嗜鹼性粒細胞趨化遷移至發炎處和隨後釋放的過敏性炎症介質，如炎症相關的趨化因子和促炎細胞因子。結果表明，沒食子酸天然植物產品可能是一個潛在的過敏性皮膚炎的治療劑，而沒食子酸和地塞米松的結合使用，可以有效降低在患者治療皮膚炎症時使用地塞米松的劑量。總結，這項研究結果揭示使用天然植物衍生產品具有更安全,高效力和副作用少的一種新治療方式。 / The worldwide prevalence of allergic diseases has been increasing gradually. Around 30 - 40% of the world population suffers from one or more allergic conditions, it is definitely a national public health issue. The incidence of Atopic Dermatitis (AD) has increased by 2-3 folds in the past 3 decades with no definitive cure, where the case is the highest during the early infancy and childhood. However, effective treatments on allergic diseases are still lacking, with most of the traditional treatment involves clinical improvement but not targeting the primary factors promoting the pathogenesis of allergic inflammation. These traditional treatments have undesirable side effects. Therefore, there has been a rising interest in the development of a safer and nonsteroid immunomodulation formula to cure the disease. / From previous clinical trails, it is revealed that children with moderate-to-severe AD treated with traditional Chinese Medicine, Pentaherbs formula (PHF), have significantly improved their quality of life, lowered the Scoring of Atopic Dermatitis (SCORAD) index and the use of topical steroids without any adverse drug effect, suggesting that PHF can be an alternative potential adjunct therapy for AD. In this present studies, we elucidated the in vitro anti‐inflammatory and anti‐allergic activities of PHF, Cortex Moutan / Danpi (DP, one of the five herbs in PHF) and gallic acid (GA, one of the main ingredients in Danpi) using human basophilic KU812 cells, with or without human dermal fibroblast, upon the activation with alarmin inflammation-related cytokine IL-33. / Human basophilic KU812 cells activated by alarmin cytokine IL-33 were used as basophil cell model for study since basophils are a crucial effector cells in allergic inflammation. Our results showed that PHF, DP and GA exhibited the anti-inflammatory and anti‐allergic activities indicated by significant suppressive effects on the intercellular adhesion molecule (ICAM)‐1 expression, the release of inflammation‐related chemokines CCL2, CCL5, CXCL8 and proinflammatory cytokine IL-6 from IL-33‐activated KU812 basophilic cells. The studies were further investigated with the combined use of synthetic steroid dexamethasone which is a common drug for AD. Among various combinations with different concentrations of dexamethasone with PHF, DP and GA, we demonstrated that the combined use of a concentration as low as 0.01 μg/ml dexamethasone and 10 μg/ml GA could further suppress ICAM‐1 expression, chemokines CCL2 and CCL5 release in IL-33 activated KU812 cells. Furthermore, gallic acid could significantly suppress the intracellular signaling molecules p38 MAPK, IκB-α and JNK in KU812 cells, thereby suggesting the underlying mechanisms for the suppressive effect on adhesion molecules expression, and the chemokines and cytokines release. Both in vivo and in vitro experiments show that PHF, DP and GA exhibit the anti-inflammatory and anti‐allergic activities in concordance to the previous clinical trials using PHF on AD children. / In order to further study the involvement of gallic acid and dexamethasone in the pathogenesis of AD, we then established an in vitro skin inflammatory cell model by co‐culturing human basophilic KU812 cells and human dermal fibroblasts mimicking the skin lesions of the AD patients. We revealed that the application of gallic acid alone could already significantly suppress the adhesion molecules expression on KU812 cell and fibroblasts, and the release of AD-related chemokines CCL2, CCL5, CXCL8 and pro-inflammatory cytokine IL-6 from the co‐culture. In addition, the combined use of dexamethasone and gallic acid showed an enhanced suppressive effect on ICAM-1 on KU812, and ICAM-1 and VCAM-1 on fibroblasts, AD‐releated chemokines CCL2 and CXCL8, and pro-inflammatory cytokine IL-6. / The above findings suggest that PHF, DP and GA are anti-inflammatory and anti-allergic natural plant products by suppressing the transmigration of basophils into the inflamed sites and the subsequent release of allergic inflammation mediators e.g. inflammation-related chemokines and proinflammatory cytokines.The results suggest that natural plant product gallic acid could be a potential therapeutic agent in treating skin inflammation in AD, and the combined use of gallic acid with dexamethasone could lower the dosage of dexamethasone used in AD patients. Together, of the results of this study shed light for a novel therapeutic modality of AD using a safer natural plant derived product with high potency and less side effects to treat AD. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Liu, Yan Ping Kelly. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 107-122). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.I / ABSTRACT --- p.III / 摘要 --- p.VI / PUBLICATIONS --- p.IX / ABBREVIATIONS --- p.XI / TABLES OF CONTENTS --- p.XIII / Chapter CHAPTER 1: --- General Introduction / Chapter 1.1 --- Allergy --- p.1 / Chapter 1.1.1 --- Definition of Allergy --- p.1 / Chapter 1.1.2 --- Allergic diseases and their prevalence --- p.2 / Chapter 1.1.3 --- Allergic inflammation and its characteristics --- p.2 / Chapter 1.1.4 --- Treatment of allergy --- p.4 / Chapter 1.1.5 --- Atopic Dermatitis --- p.7 / Chapter 1.2 --- Biology of basophils --- p.8 / Chapter 1.2.1 --- Development of basophils --- p.8 / Chapter 1.2.2 --- Morphology and phenotype --- p.9 / Chapter 1.2.3 --- Mast cells and basophils --- p.11 / Chapter 1.2.4 --- Basophils and allergic inflammation --- p.12 / Chapter 1.2.5 --- Human basophilic KU812 cell line --- p.13 / Chapter 1.3 --- Adhesion molecules in allergic inflammation --- p.14 / Chapter 1.3.1 --- Selectins --- p.14 / Chapter 1.3.2 --- Integrins --- p.16 / Chapter 1.3.3 --- Immunoglobulin gene super family --- p.16 / Chapter 1.4 --- Chemokines in allergic inflammation --- p.18 / Chapter 1.4.1 --- C chemokines --- p.18 / Chapter 1.4.2 --- CC chemokines --- p.18 / Chapter 1.4.3 --- CXC chemokines --- p.19 / Chapter 1.4.4 --- CX3C chemokines --- p.19 / Chapter 1.5 --- Cytokines in allergic inflammation --- p.20 / Chapter 1.5.1 --- Proinflammatory cytokines --- p.20 / Chapter 1.5.2 --- Anti-inflammatory cytokines --- p.23 / Chapter 1.6 --- Signal Transduction in allergic inflammation --- p.25 / Chapter 1.6.1 --- Intracellular signaling mechanisms --- p.25 / Chapter 1.6.2 --- RAS-RAF-MAPK pathway --- p.27 / Chapter 1.6.3 --- JAK/STAT pathway --- p.28 / Chapter 1.6.4 --- PI3K-Akt pathway --- p.28 / Chapter 1.6.5 --- NF-κB pathway --- p.28 / Chapter 1.7 --- Aim of Study --- p.29 / Chapter Chapter 2: --- Materials and Methods / Chapter 2.1 --- Materials --- p.32 / Chapter 2.1.1 --- Cell Culture --- p.32 / Chapter 2.1.2 --- Serum Supplements --- p.33 / Chapter 2.1.3 --- Recombinant human cytokine --- p.33 / Chapter 2.1.4 --- Dexamethasone --- p.33 / Chapter 2.1.5 --- Phosphate-buffered saline --- p.34 / Chapter 2.1.6 --- Dimethyl sulfoxide --- p.34 / Chapter 2.1.7 --- Nucleotide-binding oligomerization domain ligands --- p.34 / Chapter 2.1.8 --- BAY 117082 --- p.34 / Chapter 2.1.9 --- Cell surface and intracellular immunofluorescence staining --- p.35 / Chapter 2.1.10 --- In vitro XTT based toxicology assay kit --- p.38 / Chapter 2.1.11 --- Quantitative analysis of inflammatory mediators release --- p.38 / Chapter 2.1.12 --- Natural Products --- p.39 / Chapter 2.1.13 --- Animal Experiment --- p.40 / Chapter 2.2 --- Methods --- p.41 / Chapter 2.2.1 --- Cell Culture --- p.41 / Chapter 2.2.2 --- Preparation of plant extracts --- p.42 / Chapter 2.2.3 --- Cell toxicity of the natural products --- p.42 / Chapter 2.2.4 --- Flow cytometric analysis of cell surface expression of molecules --- p.43 / Chapter 2.2.5 --- CBA assay --- p.43 / Chapter 2.2.6 --- Flow cytometric analysis of activated intracellular molecules --- p.44 / Chapter 2.2.7 --- Allergic asthmatic mice model --- p.45 / Chapter 2.2.8 --- Statistical analysis --- p.45 / Chapter Chapter 3: --- Anti-inflammatory and anti-allergic properties of Pentaherbs formula, Danpi and Gallic acid / Chapter 3.1 --- Introduction --- p.46 / Chapter 3.1.1 --- Basophils in inflammation --- p.46 / Chapter 3.1.2 --- IL-33 --- p.47 / Chapter 3.1.3 --- Natural plant products --- p.48 / Chapter 3.1.4 --- Dexamethasone --- p.51 / Chapter 3.1.5 --- Hypothesis and aim of study --- p.52 / Chapter 3.2 --- Results --- p.54 / Chapter 3.2.1 --- Cell cytotoxicity of PHF, DP and GA on human basophilic KU812 cells --- p.54 / Chapter 3.2.2 --- Effect of adhesion molecules expression on IL-33-activated KU812 cells treated with PHF, DP and GA --- p.56 / Chapter 3.2.3 --- Effect of PHF, DP and GA on inflammation-related chemokines CCL2,CCL5, CXCL-8 production from IL-33-activated KU812 cells --- p.59 / Chapter 3.2.4 --- Effect of PHF, DP and GA on pro-inflammatory cytokine IL-6 production from IL-33-activated KU812 cells --- p.64 / Chapter 3.2.5 --- Intracellular signaling pathways involved in GA treatment on IL33-activated KU812 cells --- p.67 / Chapter 3.2.6 --- Effect on the adhesion molecules expression, chemokines and cytokines release of IL-33-activated human basophilic KU812 cells upon the combined treatment of PHF/DP/GA with dexamethasone --- p.73 / Chapter 3.2.7 --- In vivo effect of PHF and DP on Th2 and inflammatory cytokines concentration in serum or BALF in allergic inflammatory mice models --- p.76 / Chapter 3.3 --- Discussion --- p.79 / Chapter Chapter 4: --- Gallic acid and Dexamethasone in Atopic Dermatitis / Chapter 4.1 --- Introductions --- p.84 / Chapter 4.1.1 --- Atopic Dermatitis --- p.84 / Chapter 4.1.2 --- Basophils in AD --- p.86 / Chapter 4.1.3 --- Dermal fibroblasts in AD --- p.86 / Chapter 4.1.4 --- Hypothesis --- p.87 / Chapter 4.2 --- Results --- p.88 / Chapter 4.2.1 --- Effect of the combined use of GA and dexamethasone on ICAM-1 expression on KU812 cells co-cultured with fibroblasts --- p.88 / Chapter 4.2.2 --- Effect of the combined use of GA and dexamethasone on ICAM-1 and VCAM-1 expression on fibroblasts co-cultured with KU812 cells --- p.90 / Chapter 4.2.3 --- Effect on chemokines release from the co-culture upon the treatment with GA and dexamethasone --- p.93 / Chapter 4.2.4 --- Effect on cytokine release from the co-culture treated with GA and dexamethasone --- p.96 / Chapter 4.3 --- Discussions --- p.98 / Chapter Chapter 5: --- Concluding Remarks and Future Prospective / Chapter 5.1 --- Concluding remarks --- p.100 / Chapter 5.2 --- Future prospective --- p.101 / References --- p.107

Cheung Ho Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 164-175). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vi / Publications based on the work in this thesis --- p.vii / Table of content --- p.viii / Abbreviations --- p.xii / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Traditional Chinese Medicine --- p.1 / Chapter 1.1.1 --- Danshen --- p.2 / Chapter 1.1.2 --- Chemical constituents --- p.5 / Chapter 1.1.3 --- Pharmacological effects --- p.7 / Chapter 1.1.3.1 --- On blood vessels --- p.7 / Chapter 1.1.3.2 --- On blood pressure --- p.8 / Chapter 1.1.3.3 --- On heart --- p.8 / Chapter 1.1.3.4 --- On myocardial ischaemia and reperfusion --- p.9 / Chapter 1.1.3.5 --- On platelet activity --- p.10 / Chapter 1.1.3.6 --- Other actions --- p.11 / Chapter 1.1.4 --- Clinical studies --- p.12 / Chapter 1.2 --- The Vascular System --- p.13 / Chapter 1.2.1 --- The circulation network --- p.13 / Chapter 1.2.2 --- Physiology of blood vessels --- p.13 / Chapter 1.2.3 --- Control of vascular lone --- p.14 / Chapter 1.3 --- Mechanisms of Vasodilatation --- p.16 / Chapter 1.3.1 --- Endothelium derived relaxant factors (EDRFs) --- p.16 / Chapter 1.3.1.1 --- Nitric oxide (NO) --- p.16 / Chapter 1.3.1.2 --- Prostacyclin (PGI：) --- p.17 / Chapter 1.3.1.3 --- Endotheliun-derived hyperpolarization factors (EDHFs) --- p.18 / Chapter 1.3.1.3.1 --- Epoxyeicosatrienoic acids (EETs) --- p.19 / Chapter 1.3.1.3.2 --- Potassium ion (IC) --- p.20 / Chapter 1.3.1.3.3 --- Gap junction --- p.20 / Chapter 1.3.2 --- Signal transduction pathways --- p.21 / Chapter 1.3.2.1 --- Guanylyl cyclase-cGMP pathway --- p.21 / Chapter 1.3.2.2 --- Adenylyl cyclase-cAMP pathway --- p.22 / Chapter 1.3.3 --- Ion channels in vascular smooth muscle cell --- p.24 / Chapter 1.3.3.1 --- Potassium channels (K+ channels) --- p.24 / Chapter 1.3.3.2 --- Calcium channels (Ca2+ channels) --- p.24 / Chapter 1.3.3.3 --- Chloride channel (Cl channel) --- p.25 / Chapter 1.3.4 --- Receptor-operated mechanisms --- p.27 / Chapter 1.3.4.1 --- Muscarinic receptors --- p.27 / Chapter 1.3.4.2 --- Adrenoceptors --- p.27 / Chapter 1.3.4.3 --- Histamine receptors --- p.28 / Chapter 1.3.4.4 --- CGRP receptors --- p.29 / Chapter 1.3.4.5 --- Tachykinin receptors --- p.30 / Chapter 1.4 --- Aims of the studies --- p.31 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.32 / Chapter 2.1 --- Extraction of Water and Lipid-solubie Fractions from Danshen --- p.32 / Chapter 2.1.1 --- Preparation of water-soluble and lipid-soluble fractions --- p.33 / Chapter 2.2 --- Experiments on Rat Knee Joint --- p.35 / Chapter 2.2.1 --- Animals --- p.35 / Chapter 2.2.2 --- Materials --- p.35 / Chapter 2.2.3 --- Preparatory protocols --- p.37 / Chapter 2.2.3.1 --- Anaesthesia of animals --- p.37 / Chapter 2.2.3.2 --- Cannulation of trachea --- p.37 / Chapter 2.2.3.3 --- Cannulation of carotid artery --- p.38 / Chapter 2.2.3.4 --- Blood pressure measurement --- p.38 / Chapter 2.2.4 --- Measurement of knee joint blood flow --- p.39 / Chapter 2.2.4.1 --- Preparation for measurement of knee joint blood flow --- p.41 / Chapter 2.2.5 --- Experimental protocols --- p.41 / Chapter 2.2.5.1 --- Danshen on knee joint blood flow --- p.41 / Chapter 2.2.5.2 --- Antagonists on Danshen --- p.41 / Chapter 2.2.5.3 --- Positive controls --- p.43 / Chapter 2.2.6 --- Image analysis --- p.44 / Chapter 2.2.7 --- Data analysis --- p.44 / Chapter 2.3 --- Experiments on Rat Femoral Artery --- p.45 / Chapter 2.3.1 --- Animals --- p.45 / Chapter 2.3.2 --- Materials --- p.45 / Chapter 2.3.2.1 --- Chemicals --- p.45 / Chapter 2.3.2.2 --- Physiological salt solution --- p.48 / Chapter 2.3.3 --- Preparatory protocols --- p.48 / Chapter 2.3.3.1 --- Small vessel myograph --- p.48 / Chapter 2.3.3.2 --- Isolation and mounting of tissue --- p.49 / Chapter 2.3.4 --- Experimental protocols --- p.50 / Chapter 2.3.4.1 --- Studies on the vasodilator response to Danshen --- p.50 / Chapter 2.3.4.2 --- Studies of antagonists on Danshen --- p.50 / Chapter 2.3.4.2.1 --- Endothelium-dependent mechanisms --- p.51 / Chapter 2.3.4.2.2 --- Endothelium-independent mechanisms --- p.54 / Chapter 2.3.4.2.3 --- K+ channel blockers --- p.54 / Chapter 2.3.4.2.4 --- Positive controls --- p.55 / Chapter 2.3.4.3 --- Danshen on Ca2+-induced contraction --- p.56 / Chapter 2.3.5 --- Data analysis --- p.57 / Chapter CHAPTER 3 --- RESULTS --- p.58 / Chapter 3.1 --- Danshen on Rat Knee Joint Blood Flow --- p.58 / Chapter 3.1.1 --- Topical administration of Danshen --- p.58 / Chapter 3.1.2 --- Antagonists on Danshen --- p.59 / Chapter 3.1.2.1 --- Muscarinic receptor antagonist --- p.59 / Chapter 3.1.2.2 --- β-adrenoceptor antagonist --- p.60 / Chapter 3.1.2.3 --- Histamine receptor antagonists --- p.60 / Chapter 3.1.2.4 --- Nitric oxide synthase inhibitor --- p.61 / Chapter 3.1.2.5 --- Cyclo-oxygenase inhibitors --- p.62 / Chapter 3.1.2.6 --- CGRPi receptor antagonist --- p.62 / Chapter 3.1.2.7 --- NK1 receptor antagonist --- p.63 / Chapter 3.1.2.8 --- Potassium channel inhibitor --- p.64 / Chapter 3.1.2.9 --- "Combination of cyclo-oxygenase inhibitor, nitric oxide synthase inhibitor and CGRP1 receptor antagonist" --- p.64 / Chapter 3.1.3 --- Antagonists on water-soluble fraction of Danshen --- p.91 / Chapter 3.1.3.1 --- Nitric oxide synthase inhibitor --- p.91 / Chapter 3.1.3.2 --- Cyclo-oxygenase inhibitors --- p.91 / Chapter 3.1.3.3 --- CGRP1 receptor antagonist --- p.92 / Chapter 3.1.3.4 --- NK1 receptor antagonist --- p.92 / Chapter 3.1.3.5 --- Potassium channel inhibitor --- p.92 / Chapter 3.2 --- Danshen on Rat Femoral Artery --- p.99 / Chapter 3.2.1 --- Danshen on precontracted arterial ring --- p.99 / Chapter 3.2.2 --- Endothelium-dependent mechanisms --- p.106 / Chapter 3.2.3 --- Endothelium-independent mechanisms --- p.114 / Chapter 3.2.4 --- K+ channel blockers --- p.119 / Chapter 3.2.4.1 --- Effect on Danshen --- p.119 / Chapter 3.2.4.2 --- Effect on water-soluble and lipid-soluble fractions of Danshen --- p.121 / Chapter 3.2.4.3 --- Effect on Danshensu --- p.122 / Chapter 3.2.5 --- Danshen on Ca2+-induced contractions --- p.133 / Chapter CHAPTER 4 --- DISCUSSION --- p.138 / Chapter 4.1 --- In Vivo Studies of Danshen on Rat Knee Joint Blood Flow --- p.139 / Chapter 4.2 --- In Vitro Studies of Danshen on Isolated Rat Femoral Artery --- p.148 / Chapter 4.2.1 --- Comparisons of the use of different precontractors --- p.148 / Chapter 4.2.2 --- Investigations on endothelium-dependent mechanisms --- p.151 / Chapter 4.2.3 --- Investigations on endothelium-independent mechanisms --- p.152 / Chapter 4.2.4 --- Effects of K+ channel blockers --- p.154 / Chapter 4.2.5 --- Inhibition of Ca2+ influx in vascular smooth muscle --- p.157 / Chapter 4.3 --- Comparisons of Results from In Vivo and In Vitro Studies --- p.159 / Chapter 4.4 --- Future Studies --- p.161 / Chapter 4.5 --- Conclusion --- p.162 / REFERENCES --- p.164

Finally, the neuroprotective effects of TGP against corticosterone-induced neurotoxicity in rat pheochromocytoma (PC12) cells, an in vitro experimental model of depression were studied. The results showed TGP treatment dose-dependently protected the cells against corticosterone-induced toxicity. The cytoprotection afforded by TGP treatment was shown to be associated with an enhanced antioxidant activity, and increased expressions of neurotrophins including brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3. / Secondly, the antidepressant-like effect of TGP was evaluated by a rat model of depression induced by chronic unpredictable mild stress (CUMS). The results showed that a 5-week CUMS caused depression-like behavior in rats, as indicated by a significant decreases in sucrose consumption (assessed by sucrose preference test) and locomotor activity (assessed by open-field test), and an increase in immobility time (assessed by forced swim test). Intragastric administration of TGP during the five weeks of CUMS procedure significantly suppressed these behavioral changes induced by CUMS. / Taken together, the results confirmed the antidepressant-like effect of TGP. The antidepressive action of TGP may be mediated by the modulation of the hypothalamic-pituitary-adrenal axis function, the inhibition of oxidative stress, and the up-regulation of neurotrophins, thereby leading to the neuroprotective effects. / The antidepressant-like effect of TGP was firstly evaluated by the behavioral despair test, forced swim test and tail suspension test. The results showed that intragastric administration of TGP caused a significant reduction of immobility time in both forced swim and tail suspension tests in mice. TGP treatment also significantly reduced the duration of immobility time in the forced swim test in rats. / The root of Paeonia lactiflora Pall. (Family: Ranunculaceae), commonly known as peony, is a component herb of many traditional formulae for the treatment of depression-like disorders. Previous studies have demonstrated the antidepressive effect of peony extract in mouse models of depression. Total glycosides of peony (TGP) is regarded as the major active ingredients of peony. The present study aims to confirm the antidepressive potential of TGP and evaluate its action mechanisms. / Thirdly, the neuroprotective effects of TGP on CUMS-treated rats and its possible mechanisms were investigated. The results showed that treatment with TGP for 5 weeks produced neuroprotective effects on the hippocampus of CUMS-treated rats. This effect was associated with the attenuation of hypothalamic-pituitary-adrenal axis hyperactivation (characterized by a decreased serum corticosterone level and an increased hippocampal glucocorticoid receptor expression), an inhibition of oxidative stress, and up-regulation of neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3 in the hippocampus. / Mao, Qingqiu. / Adviser: Che Chun-Tao. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 158-186). / 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.

Chung Hoi Sing. / "August 2001." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 186-204) / 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.

Bioassays of total alkaloids of S. tuberosa samples representing the four types of chemical profiles were conducted on guinea pigs using citric acid aerosol for inducing cough. These results demonstrated their antitussive properties and thus suggested the possibility of other antitussive alkaloids than neotuberostemonine in S. tuberosa. So it became necessary to identify the major components in the samples of S. tuberosa representing the four types of chemical profiles. / Bioassays on guinea pigs of the four major components of S. tuberosa demonstrated their antitussive properties. Except a lower potency in tuberostemonine, antitussive effects of croomine and stemoninine showed similar or even stronger potency than neotuberostemonine at 25 and 50 mg/kg by intragastric administration. These four antitussive alkaloids could be used as lead compounds for the development of new antitussive drugs and as bioactive markers in quality control of the herb S. tuberosa and related products. / Cough is an airway defensive reflex, which is responsible for keeping the airway free of obstruction and harmful substances. As the commonest symptom for which medical advices is sought, enormous costs are spent on cough treatments. Regretfully, currently used antitussives are less than satisfactory due to their low potency or obvious side effects. So it is necessary to continue developing new and better antitussives. / Electrical stimulation of the superior laryngeal nerve on guinea pigs at 100 mg/kg through intraperitoneal administration indicated that croomine acted on the central pathway of cough reflex accompanied by respiratory depression. On the other hand, neotuberostemonine, tuberostemonine and stemoninine acted on the peripheral pathway without any observable side effects. These three alkaloids could be promising for developing new peripherally acting antitussives. Further, tuberostemonine was tested on primary cultured nodose ganglion cells by patch clamp and, at 0.5 mM, was demonstrated to significantly decrease the change amplitude of membrane potential induced by 1.0 mM citric acid solution. The results suggested that tuberostemonine could depress electrical excitability of nodose ganglion cells and thus inhibit the afferent signals of cough reflex leading to its antitussive activity. / In order to determine if the different chemical profiles of Stemona total alkaloids were the result of species difference or variations within the same species, the three Stemona species registered in the PRC Pharmacopoeia were collected from different areas in China. They were planted to flowering in our greenhouse and authenticated by both reproductive and vegetative characters. Microscopic examination on these authentic species showed that tuberous roots of S. tuberosa differed by epidermal cells with smooth outer surface and fibers in the cortex and pith from those of S. japonica and S. sessilifolia. The chemical profiles of authentic samples were analyzed on a HPLC-ELSD system. The results indicated that species-specific differences were present in the HPLC profiles of the three Stemona species. Within S. tuberosa, the chemical profiles of different samples were found to be very variable and they could be roughly divided into four types in the tested samples. Neotuberostemonine was present in one of the four types of S. tuberosa. Since antitussive effects of neotuberostemonine were demonstrated by Chung et al. (2003), it became necessary to determine if the samples containing alkaloids other than neotuberostemonine had antitussive properties. / The Chinese herb Radix Stemonae (Baibu) has long been used as an antitussive in Chinese medicine for some two thousand years. Its source materials, according to the Pharmacopoeia of the People's Republic of China (PRC Pharmacopoeia), come from the tuberous roots of three Stemona species, namely, S. japonica (Blume) Miq., S. sessilifolia (Miq.) Miq. and S. tuberosa Lour. However, hardly any experimental study is available to document their antitussive functions. Chung et al. (2003) reported that the antitussive components of S. tuberosa were neotuberostemonine and related stenine type Stemona alkaloids. And the antitussive potency of neotuberostemonine through intraperitoneal administration was reported to be comparable to codeine but not involving opioid receptors. In continuation with the study of the antitussive properties of the herb, it was found that total alkaloids of different samples of the herb appeared to vary in chemical profiles, whereas neotuberostemonine was found in only a few samples. / The major components of S. tuberosa including stemoninine, croomine and neotuberostemonine were isolated and determined by spectroscopic methods. It was the first time to isolate croomine from Stemona species, lending support to retaining the two genera Stemona and Croomina in the family Stemonaceae according to chemotaxonomy. Tuberostemonine, another major component of S. tuberosa was also isolated and determined in our team. Neotuberostemonine and tuberostemonine were two isomers but mutually exclusive in our tested samples. Moreover, these major components of S. tuberosa belonged to three types in molecular structure. Stemoninine was stemonamide type, croomine tuberostemospironine type and both neotuberostemonine and tuberostemonine stenine type. These results suggested that antitussive effects of S. tuberosa might be related to the components belonging to these three molecular types. / Xu Yantong. / "March 2006." / Adviser: Paul But. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6231. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 137-155). / 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.

Chan Wai-Lung, William. / Thesis submitted in: December 2000. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 124-131). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (Chinese Version) --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Tables --- p.ix / List of Figures --- p.xii / List of Abbreviations --- p.xvi / Chapter 1 --- Introduction --- p.1 / Literature Review --- p.4 / Chapter 1.1 --- A Brief Introduction of Cancer --- p.4 / Chapter 1.2 --- Natural Products as a Drug --- p.5 / Chapter 1.2.1 --- Development of terrestrial plants as a drug --- p.6 / Chapter 1.2.1.1 --- Anticancer drugs from terrestrial plants and Chinese medicinal herbs --- p.7 / Chapter 1.2.2 --- Development of marine organisms as a drug --- p.8 / Chapter 1.2.2.1 --- Anticancer drugs from marine organisms --- p.9 / Chapter 1.3 --- Anticlastogenic Study - an Anticancer Study --- p.10 / Chapter 1.3.1 --- Anticlastogenesis mechanisms study --- p.11 / Chapter 1.3.2 --- In vivo anticlastogenic study --- p.13 / Chapter 1.4 --- Anticlastogenic Study of Chinese Medicinal Herbs and Marine Algae --- p.17 / Chapter 1.4.1 --- Selection of nine Chinese medicinal herbs and three marine algae for anticlastogenic screening --- p.18 / Chapter 1.5 --- Methods of Investigation --- p.20 / Chapter 1.5.1 --- Extraction methods --- p.20 / Chapter 1.5.2 --- Single cell gel electrophoresis (Comet assay) --- p.21 / Chapter 2 --- Materials and Methods --- p.27 / Chapter 2.1 --- Materials --- p.27 / Chapter 2.1.1 --- Chinese medicinal herbs --- p.27 / Chapter 2.1.2 --- Marine algae --- p.27 / Chapter 2.1.3 --- Animals --- p.27 / Chapter 2.1.4 --- Chemicals and solutions --- p.28 / Chapter 2.2 --- Methods --- p.31 / Chapter 2.2.1 --- Crude extraction of natural products --- p.31 / Chapter 2.2.1.1 --- Water extraction of Chinese herbs --- p.31 / Chapter 2.2.1.2 --- Water extraction of marine algae --- p.31 / Chapter 2.2.2 --- Test for the effective dosage of clastogen ethyl methanesulfonate (EMS) to BALB/c mice --- p.31 / Chapter 2.2.2.1 --- In vitro test --- p.32 / Chapter 2.2.2.2 --- In vivo test --- p.32 / Chapter 2.2.3 --- Anticlastogenic bioassays --- p.33 / Chapter 2.2.3.1 --- In vitro anticlastogenic screening --- p.33 / Chapter 2.2.3.2 --- In vitro anticlastogenic mechanisms investigation --- p.33 / Chapter 2.2.3.3 --- In vivo anticlastogenic screening --- p.34 / Chapter 2.2.3.4 --- Different in vivo anticlastogenic treatment schedules --- p.35 / Chapter 2.2.4 --- Single cell gel electrophoresis assay (Comet assay) --- p.36 / Chapter 2.2.5 --- White blood cell viability determination --- p.37 / Chapter 2.2.6 --- Statistical analysis --- p.38 / Chapter 3 --- Results --- p.40 / Chapter 3.1 --- Extraction amount of different natural products and cell viability checking --- p.40 / Chapter 3.1.1 --- Chinese medicinal herbs --- p.40 / Chapter 3.1.2 --- Seaweeds --- p.40 / Chapter 3.1.3 --- Cell viability --- p.42 / Chapter 3.2 --- Effective dosage of clastogen EMS to BALB/c mice peripheral white blood cells --- p.42 / Chapter 3.2.1 --- In vitro --- p.42 / Chapter 3.2.2 --- In vivo --- p.42 / Chapter 3.3 --- In vitro anticlastogenic screen test and mechanisms investigation --- p.44 / Chapter 3.3.1 --- In vitro anticlastogenic screen test --- p.44 / Chapter 3.3.1.1 --- Chinese herbs --- p.44 / Chapter 3.3.1.2 --- Seaweeds --- p.53 / Chapter 3.3.2 --- In vitro anticlastogenic mechanisms investigation --- p.55 / Chapter 3.3.2.1 --- H. dilatata --- p.56 / Chapter 3.3.2.2 --- S. angustifolium --- p.56 / Chapter 3.3.2.3 --- S. siliquastrum --- p.63 / Chapter 3.4 --- In vivo anticlastogenic screen test and mechanisms investigation --- p.66 / Chapter 3.4.1 --- In vivo anticlastogenic screen test --- p.66 / Chapter 3.4.1.1 --- Chinese herbs --- p.66 / Chapter 3.4.1.2 --- Seaweeds --- p.73 / Chapter 3.4.2 --- Different treatment methods in in vivo anticlastogenic test --- p.86 / Chapter 3.4.2.1 --- Simultaneous application method --- p.86 / Chapter 3.4.2.2 --- Pre-drug treatment method --- p.91 / Chapter 3.4.2.3 --- Post drug treatment method --- p.91 / Chapter 4 --- Discussion --- p.94 / Chapter 4.1 --- Cell viability and water extracts in Chinese medicinal herbs and marine algae --- p.94 / Chapter 4.2 --- Clastogenic effect of EMS to pWBCs of BALB/c mice --- p.94 / Chapter 4.3 --- In vitro anticlastogenic screen test of nine water extracts of Chinese medicinal herbs and three water extracts of marine algae --- p.99 / Chapter 4.4 --- In vitro anticlastogenic mechanisms investigation of three \03 marine algae extracts --- p.103 / Chapter 4.5 --- In vivo anticlastogenic screen test of Chinese herbs extracts and seaweeds extracts --- p.108 / Chapter 4.6 --- Different administration methods in in vivo anticlastogenic test --- p.115 / Chapter 4.6.1 --- Intraperitoneal route of administration --- p.115 / Chapter 4.6.2 --- In vivo pre- and post-treatment methods --- p.116 / Chapter 5 --- Summary and Conclusion --- p.120 / References --- p.124

Cheung, Ching Mei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 151-162). / Abstracts in English and Chinese. / ABSTRACT --- p.I / 論文摘要 --- p.IV / ACKNOWLEDGEMENT --- p.VI / TABLE OF CONTENTS --- p.VII / ABBREVIATIONS --- p.X / Chapter Chapter 1 --- p.1 / GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- DANSHEN --- p.1 / Chapter 1.1.1 --- LIPID-SOLUBLE COMPOUNDS EXTRACTED FROM DANSHEN --- p.2 / Chapter 1.1.1.1 --- TANSHINONE I --- p.2 / Chapter 1.1.1.2 --- TANSHINONE IIA --- p.3 / Chapter 1.1.1.3 --- CRYPTOTANSHINONE --- p.3 / Chapter 1.1.1.4 --- DIHYDROTANSHINONE --- p.4 / Chapter 1.1.2 --- WATER-SOLUBLE COMPOUNDS EXTRACTED FROM DANSHEN --- p.4 / Chapter 1.1.2.1 --- DANSHENSU --- p.4 / Chapter 1.1.2.2 --- SALVIANOLIC ACID B --- p.5 / Chapter 1.2 --- DRUG-DRUG INTERACTIONS --- p.5 / Chapter 1.2.1 --- PROBLEMS ASSOCIATED WITH HERBAL ADMINISTRATION --- p.5 / Chapter 1.2.2 --- HERB-DRUG INTERACTIONS --- p.7 / Chapter 1.2.2.1 --- ST. JOHŃةS WORT-DRUG INTERACTIONS --- p.8 / Chapter 1.2.2.2 --- WARFARIN-HERB INTERACTIONS --- p.9 / Chapter 1.2.2.3 --- DANSHEN-WARFARIN INTERACTIONS --- p.10 / Chapter 1.2.2.4 --- DANSHEN-DRUG INTERACTIONS --- p.11 / Chapter 1.3 --- CYTOCHROME P450 ENZYMES (CYP) --- p.12 / Chapter 1.3.1 --- CYTOCHROME P4502E1 --- p.13 / Chapter 1.4 --- AIMS OF STUDY --- p.17 / Chapter Chapter 2 --- p.21 / EFFECTS OF DANSHEN AND SOME IF ITS ACTIVE COMPONENTS ON CHLORZOXAZONE METABOLISM IN RAT AND HUMAN LIVER MICROSOMES IN VITRO --- p.21 / Chapter 2.1 --- INTRODUCTION --- p.21 / Chapter 2.2 --- MATERIALS AND METHODS --- p.23 / Chapter 2.2.1 --- CHEMICALS AND REAGENTS --- p.23 / Chapter 2.2.2 --- PREPARATION OF AQUEOUS FRACTION OF DANSHEN --- p.23 / Chapter 2.2.3 --- PREPARATION OF ETHANOLIC FRACTION OF DANSHEN --- p.23 / Chapter 2.2.4 --- ANIMALS --- p.24 / Chapter 2.2.5 --- PREPARATION OF RAT LIVER MICROSOMES --- p.25 / Chapter 2.2.6 --- POOLED HUMAN LIVER MICROSOMES --- p.25 / Chapter 2.2.7 --- PROTEIN ASSAY --- p.25 / Chapter 2.2.8 --- MICROSOMAL INCUBATION --- p.26 / Chapter 2.2.8.1 --- RAT LIVER MICROSOMES --- p.26 / Chapter 2.2.8.2 --- HUMAN LIVER MICROSOMES --- p.26 / Chapter 2.2.9 --- INHIBITION KINETICS STUDIES --- p.27 / Chapter 2.2.9.1 --- RAT LIVER MICROSOMES --- p.27 / Chapter 2.2.9.2 --- HUMAN LIVER MICROSOMES --- p.27 / Chapter 2.2.10 --- HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) ANALYSIS --- p.28 / Chapter 2.2.11 --- DATA ANALYSIS --- p.28 / Chapter 2.3 --- RESULTS --- p.31 / Chapter 2.3.1 --- EFFECT OF DANSHEN AND TANSHINONES ON RAT CYP2E1 ACTIVITY IN VITRO / Chapter 2.3.1.1 --- SUMMARY --- p.57 / Chapter 2.3.2 --- EFFECT OF DANSHEN AND TANSHINONES ON HUMAN CYP2E1 ACTIVITYIN VITRO --- p.58 / Chapter 2.3.2.1 --- SUMMARY --- p.84 / Chapter 2.4 --- DISCUSSION --- p.85 / Chapter Chapter 3 --- p.93 / EFFECTS OF DANSHEN ON CYTOCHROME P450 PROTEIN EXPRESSION AND METABOLISM OF MODEL CYP2E1 PROBE SUBSTRATE IN THE RAT IN VIVO --- p.93 / Chapter 3.1 --- INTRODUCTION --- p.93 / Chapter 3.2 --- MATERIALS AND METHODS --- p.97 / Chapter 3.2.1 --- CHEMICALS AND REAGENTS --- p.97 / Chapter 3.2.2 --- ANIMALS --- p.97 / Chapter 3.2.3 --- EFFECTS OF DANSHEN TREATMENTS ON PHARMACOKINETICS OF CHLORZOXAZONE IN RATS IN VIVO --- p.98 / Chapter 3.2.3.1 --- "ACUTE, 3-DAY AND 14-DAY TREATMENTS WITH WHOLE DANSHEN EXTRACT" --- p.98 / Chapter 3.2.3.2 --- PLASMA EXTRACTION --- p.99 / Chapter 3.2.3.3 --- HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) ANALYSIS --- p.99 / Chapter 3.2.4 --- EFFECTS OF 3-DAY AND 14-DAY DANSHEN TREATMENTS ON CYP2E1 PROTEIN EXPRESSION --- p.101 / Chapter 3.2.4.1 --- PREPARATION OF RAT LIVER MICROSOMES FOR WESTERN BLOTTING --- p.101 / Chapter 3.2.4.2 --- PROTEIN ASSAY --- p.101 / Chapter 3.2.4.3 --- WESTERN BLOT --- p.102 / Chapter 3.2.5 --- DATA ANALYSIS --- p.103 / Chapter 3.3 --- RESULTS --- p.105 / Chapter 3.3.1 --- EFFECTS OF WHOLE DANSHEN EXTRACT ON RAT CYP2E1 ACTIVITIES IN VIVO --- p.105 / Chapter 3.3.1.1 --- EFFECTS OF ACUTE TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.105 / Chapter 3.3.1.2 --- EFFECTS OF 3-DAY TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.106 / Chapter 3.3.1.3 --- EFFECTS OF 14-DAY TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.107 / Chapter 3.3.2 --- EFFECTS OF WHOLE DANSHEN EXTRACT ON RAT CYP2E1 EXPRESSION .… --- p.137 / Chapter 3.3.3 --- SUMMARY --- p.140 / Chapter 3.4 --- DISCUSSION --- p.141 / CHAPTER 4 --- p.145 / GENERAL DISCUSSION --- p.145 / REFERENCES --- p.151

Wong, Ka Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 177-189). / Abstracts in English and Chinese; includes Chinese. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vii / List of Appendices --- p.xi / List of Tables --- p.xii / List of Figures --- p.xiv / Abbreviations --- p.xvi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Background to the study --- p.2 / Chapter 1.2.1 --- Epidemiology of cancer --- p.2 / Chapter 1.2.1.1 --- Incidence and mortality in the World --- p.2 / Chapter 1.2.1.2 --- Incidence and mortality in Hong Kong --- p.4 / Chapter 1.2.2 --- Prevalence of Traditional Chinese Medicine (TCM) --- p.5 / Chapter 1.2.3 --- Prevalence of Traditional Chinese Medicine (TCM) in cancer --- p.6 / Chapter 1.2.4 --- Development of TCM in Hong Kong --- p.7 / Chapter 1.3 --- Theoretical rationale of the study --- p.8 / Chapter 1.4 --- Significance of the study --- p.11 / Chapter Chapter 2 --- Literature Review --- p.13 / Chapter 2.1 --- Introduction --- p.13 / Chapter 2.2 --- The concept of Advanced Cancer --- p.13 / Chapter 2.2.1 --- Pathology of Advanced Cancer --- p.14 / Chapter 2.2.1.1 --- Metastatic Cancer --- p.14 / Chapter 2.2.2 --- Sign and Symptoms of Advanced Cancer --- p.19 / Chapter 2.2.3 --- Diagnosis of Advanced Cancer --- p.19 / Chapter 2.2.4 --- Current Treatment for Advanced Cancer --- p.21 / Chapter 2.2.5 --- Limitation of Current Treatments --- p.24 / Chapter 2.3 --- Diagnosis and Treatment by TCM of Advanced Cancer --- p.26 / Chapter 2.3.1 --- (Advanced) Cancer from the TCM perspectives --- p.26 / Chapter 2.3.2 --- Diagnosis by TCM of Advanced Cancer --- p.27 / Chapter 2.3.3 --- Treatment by TCM of Advanced Cancer --- p.28 / Chapter 2.4 --- Current Evidences about the Clinical Effectiveness of TCM on Cancer Patients --- p.29 / Chapter 2.5 --- The concept of Health-related Quality of Life (HRQOL) --- p.35 / Chapter 2.5.1 --- The importance of HRQOL to cancer patients --- p.35 / Chapter 2.5.2 --- HRQOL instruments --- p.37 / Chapter 2.5.2.1 --- EORTC QLQ-C30 --- p.38 / Chapter 2.5.2.2 --- SF-36 --- p.39 / Chapter 2.6 --- Summary of Literature Review --- p.40 / Chapter 2.7 --- The research questions --- p.41 / Chapter 2.8 --- Research Hypotheses --- p.42 / Chapter 2.9 --- The design of TCM protocol --- p.42 / Chapter Chapter 3 --- Methodology --- p.45 / Chapter 3.1 --- Introduction --- p.45 / Chapter 3.2 --- Protocol --- p.45 / Chapter 3.2.1 --- Study Design --- p.46 / Chapter 3.2.2 --- Selection of Participants --- p.46 / Chapter 3.2.2.1 --- Inclusion criteria --- p.48 / Chapter 3.2.2.2 --- Exclusion criteria --- p.49 / Chapter 3.2.3 --- Sample size calculation --- p.50 / Chapter 3.2.4 --- Setting --- p.51 / Chapter 3.2.5 --- Interventions --- p.51 / Chapter 3.2.5.1 --- Treatment --- p.51 / Chapter 3.2.5.2 --- Medication and dose/dosage --- p.52 / Chapter 3.2.5.3 --- Treatment Assignment --- p.55 / Chapter 3.2.5.4 --- Concurrent Medications --- p.56 / Chapter 3.2.6 --- Procedure and Methods --- p.56 / Chapter 3.2.6.1 --- Informed Consent --- p.56 / Chapter 3.2.6.2 --- Documentation --- p.57 / Chapter 3.2.6.3 --- Assessment Procedure --- p.57 / Chapter 3.2.7 --- Outcome Measurements --- p.62 / Chapter 3.2.7.1 --- Survey Questionnaire --- p.62 / Chapter 3.2.7.2 --- Quality of life (QOL) instruments --- p.62 / Chapter 3.2.7.3 --- Global Ratings --- p.64 / Chapter 3.2.7.4 --- Physical Examination and Laboratory tests --- p.65 / Chapter 3.2.8 --- Safety Considerations --- p.66 / Chapter 3.2.8.1 --- Adverse Events (AE) --- p.66 / Chapter 3.2.8.2 --- Serious Adverse Event (SAE) --- p.66 / Chapter 3.2.8.3 --- Causality Assessment --- p.67 / Chapter 3.2.9 --- Ethical consideration --- p.68 / Chapter 3.2.10 --- Data Collection --- p.69 / Chapter 3.3 --- Data analysis --- p.69 / Chapter 3.4 --- Expected Outcomes of Study --- p.71 / Chapter Chapter 4 --- Results --- p.72 / Chapter 4.1 --- Study Progress --- p.72 / Chapter 4.2 --- The Participants --- p.72 / Chapter 4.3 --- Clinical characteristics and Socio-demographics of Participants --- p.75 / Chapter 4.4 --- Main Outcome - Quality of Life --- p.78 / Chapter 4.4.1 --- QLQ-C30 --- p.79 / Chapter 4.4.1.1 --- Scoring and Transforming of items into scales --- p.79 / Chapter 4.4.1.2 --- Changes of Individual Scale at Different Visits --- p.80 / Chapter 4.4.1.3 --- Clinical significance of Scales --- p.98 / Chapter 4.4.2 --- SF-36 --- p.104 / Chapter 4.4.2.1 --- Scoring and Transforming of items into scales --- p.104 / Chapter 4.4.2.2 --- Changes of Individual Scale at Different Visits --- p.104 / Chapter 4.4.2.3 --- SF-36 Summary Scales --- p.113 / Chapter 4.4.3 --- Correlation of QLQ-C30 and SF-36 --- p.115 / Chapter 4.5 --- Measurement of Physical examination --- p.117 / Chapter 4.5.1 --- Body Weight --- p.117 / Chapter 4.6 --- Measurement of Laboratory Blood tests --- p.118 / Chapter 4.6.1 --- "Comparison of CBC, RFT, LFT and LD" --- p.118 / Chapter 4.6.2 --- Tumor Markers --- p.120 / Chapter 4.7 --- Adverse Events and Serious Adverse Events --- p.121 / Chapter 4.8 --- Global Ratings --- p.123 / Chapter 4.8.1 --- Global Rating 1 - Severity of Disease --- p.123 / Chapter 4.8.2 --- Global Rating 2 - Global Disease Status --- p.124 / Chapter 4.8.2.1 --- Change in Global Disease Status --- p.125 / Chapter 4.8.2.2 --- Agreement between RCMP and clinician --- p.125 / Chapter 4.8.2.3 --- Patients' perception after treatment --- p.126 / Chapter 4.9 --- Distribution of TCM patterns and Chinese herbal medicines --- p.127 / Chapter 4.10 --- Survival Rate --- p.132 / Chapter 4.11 --- Conclusion --- p.133 / Chapter Chapter 5 --- Discussion --- p.135 / Chapter 5.1 --- Conclusion on findings --- p.135 / Chapter 5.2 --- Baseline profile of participants --- p.137 / Chapter 5.3 --- Feasibility of TCM on advanced cancer patients --- p.139 / Chapter 5.3.1 --- Recruitment of Participants --- p.139 / Chapter 5.3.2 --- Compliance of participants to the study schedule --- p.140 / Chapter 5.4 --- Health-related Quality of Life --- p.142 / Chapter 5.5 --- Safety of TCM --- p.149 / Chapter 5.6 --- Chinese medicine practitioner vs Western medicine doctor --- p.150 / Chapter 5.7 --- TCM pattern differentiation and treatment --- p.151 / Chapter 5.8 --- Implication of study --- p.154 / Chapter 5.8.1 --- Clinical implication --- p.154 / Chapter 5.8.2 --- Policy implication --- p.154 / Chapter 5.9 --- Limitations of the study --- p.155 / Chapter 5.10 --- Recommendations for further studies --- p.157 / Chapter 5.11 --- Overall Conclusion --- p.158 / Appendices --- p.160 / References --- p.177