Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 121-140).

and senkyunolide A were found as the three major compounds in all herbal samples investigated. In addition, great variations in both total and individual content of each of the ten main components investigated were observed in samples of different origins and those collected from a GAP developing base in the same or different years, suggesting the necessity of a thorough quality control for Rhizoma Chuanxiong. / Extraction of the main ingredients from Rhizoma Chuanxiong by supercritical fluid extraction using CO2 was investigated. An appropriate SCFE method for Chuanxiong was developed with the mild conditions for the extraction of the unstable components. The method provided a high recovery and adequate reproducibility, and may be suitable for large-scale industry extraction of Chuanxiong. / Firstly, a total of sixteen ingredients were identified from Chuanxiong by HPLC-UV-MS and HPLC-UV analyses. Among them, ten ingredients were determined to be the main components in Chuanxiong. A simple, sensitive and specific HPLC-UV method was developed, for the first time, to simultaneously qualitatively and quantitatively determine twelve ingredients, including the identified ten main ingredients, plus vanillin and tetramethylpyrazine (TMP), which although were not found in the present study, had also been reported to be present in Rhizoma Chuanxiong. The developed assay was fully validated and provided adequate accuracy and reproducibility for all compounds analyzed. It was applied successfully to simultaneously quantify all main constituents in different Chuanxiong samples. TMP and vanillin were not detected, while Z-ligustilide, coniferylferulate. / Furthermore, a comprehensive stability study was carried out for the first time with the three major components senkyunolide A, coniferylferulate, Z-ligustilide and the main ingredient 3-butylidenephthalide, in pure form or Chuanxiong extract obtained from supercritical fluid extraction using CO 2 (SCFE) under different conditions. Results showed that both sun light and elevated temperature led to degradations of these components to different extents. Owing to such thermal and light instability, post-harvest drying and processing procedures could significantly alter the chemical profile of Chuanxiong herb, and thus also need to be well controlled. / In conclusion, analytical and pharmacokinetic studies of the main chemical ingredients in Rhizoma Chuanxiong were systematically conducted. The results revealed, for the first time, that senkyunolide A, Z-ligustilide and 3-butylidenephthalide might be the primary chemical ingredients contributing to the beneficial effects of Chuanxiong. / Oral bioavailability was about 8%, 3% and 20% for senkyunolide A, Z-ligustilide and 3-butylidenephthalide, respectively. Instability in the gut mainly contributed to a low oral bioavailability of senkyunolide A. First-pass metabolism in the liver also contributed to the low oral bioavailability but to a much lower extent. For Z-ligustilide, extensive first-pass metabolism in the liver and degradation in the stomach only partly accounted for its poor oral bioavailability, while other gut factors involved are still unknown. In the case of 3-butylidenephthalide, its low oral bioavailability was attributed to extensive first-pass metabolism in both the gut and the liver. / Pharmacokinetic fates of the main ingredients in Chuanxiong SCFE extract were firstly evaluated in rats. After a single intravenous and oral administration, only senkyunolide A, Z-ligustilide and 3-butylidenephthalide were determined as the main herb related components in plasma. Coniferylferulate, although it is one of the abundant principles in the herb, was not detected in the plasma even immediately after dosing. / Pharmacokinetic profiles of senkyunolide A, Z-ligustilide and 3-butylidenephthalide were further elucidated individually in rats. All three compounds exhibited rapid absorption, extensive distribution, and rapid elimination. The pharmacokinetic profile of senkyunolide A followed a dose-independent pattern, whereas Z-ligustilide exhibited dose-dependent kinetics. 3-Butylidenephthalide underwent enterohepatic re-circulation. / Rhizoma Chuanxiong is derived from the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). In China, it has been widely prescribed for the treatment of cerebro- and cardio-vascular diseases for thousands of years. However, its chemical and pharmacological basis is poorly understood. In the present study, analytical methods for qualitative and quantitative determination of the main chemical components in Chuanxiong herb were developed. Furthermore, pharmacokinetic profiles of the main chemical ingredients in Chuanxiong were systematically investigated in rats for the first time. / The metabolic profiles of senkyunolide A, Z-ligustilide and 3-butylidenephthalide were investigated both in vivo and in vitro. Oxidation and hydration were found to be the main metabolic pathways for all three compounds. In addition, glutathione conjugation of senkyunolide A and Z-ligustilide also occurred in the rat. A novel metabolite 3-hydroxy-3-butylphthalide was identified as the major metabolite of 3-butylidenephthalide generated by a direct hydration, and was shown to have significantly higher plasma levels than those of the parent compound. Furthermore, the main metabolites detected in the plasma of rats administered with Chuanxiong extract were generated from senkyunolide A, Z-ligustilide and 3-butylidenephthalide. / Yan Ru. / "May 2005." / Adviser: Ge Lin. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1583. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 244-255). / 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.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 164-179).

by Cheng Yuk Kwan, Anna. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 104-112). / Acknowledgements / Table of Contents --- p.i / Abbreviations --- p.iv / Abstract --- p.vi / List of figures --- p.ix / List of tables --- p.xi / Chapter Chapter One: --- Introduction / Chapter 1.1 --- Objective and scope of the project --- p.1 / Chapter 1.2 --- Literature review of Mimosa pudica / Chapter 1.2.1 --- Morphology of Mimosa pudica --- p.3 / Chapter 1.2.2 --- Chemistry of Mimosa pudica --- p.5 / Chapter 1.2.3 --- Uses in traditional medicine --- p.5 / Chapter 1.2.4 --- Clinical and pharmacological studies of Mimosa pudica --- p.6 / Chapter 1.2.5 --- Toxicology of Mimosa pudica --- p.8 / Chapter 1.2.6 --- Characteristics and toxicology of mimosine --- p.9 / Chapter 1.3 --- Immunomodulation / Chapter 1.3.1 --- Overview of the immune system --- p.11 / Chapter 1.3.2 --- Strategies on the study of immunomodulation of Mimosa pudica --- p.13 / Chapter 1.4 --- Toxicology / Chapter 1.4.1 --- Principles of the toxicological assays / Chapter 1.4.1.1 --- LD50 --- p.17 / Chapter 1.4.1.2 --- Enzyme assays --- p.18 / Chapter 1.4.1.3 --- Subacute toxicity test --- p.24 / Chapter 1.4.1.4 --- Reproductive toxicity test --- p.25 / Chapter Chapter Two: --- Materials and methods / Chapter 2.1 --- Materials / Chapter 2.1.1 --- Mimosa pudica --- p.27 / Chapter 2.1.2 --- Animals --- p.27 / Chapter 2.1.3 --- Chemicals --- p.28 / Chapter 2.2 --- Methods / Chapter 2.2.1 --- Extraction of Mimosa pudica --- p.32 / Chapter 2.2.2 --- Assays for the immunomodulatory effects of Mimosa pudica / Chapter 2.2.2.1 --- Cell preparation / Chapter a) --- Splenocytes --- p.35 / Chapter b) --- Thymocytes --- p.35 / Chapter c) --- Macrophages --- p.36 / Chapter 2.2.2.2 --- Splenocyte proliferation --- p.37 / Chapter 2.2.2.3 --- Thymocyte proliferation --- p.38 / Chapter 2.2.2.4 --- Phagocytic activity of macrophages --- p.39 / Chapter 2.2.2.5 --- Release of IL-1 by macrophages --- p.40 / Chapter 2.2.2.6 --- Plaque forming cells --- p.41 / Chapter 2.2.2.7 --- Restoration on splenocyte blastogenesis of old mice --- p.42 / Chapter 2.2.3 --- Assays for the toxicity of Mimosa pudica / Chapter 2.2.3.1 --- LD50 --- p.43 / Chapter 2.2.3.2 --- Enzyme assays --- p.43 / Chapter 2.2.3.3 --- Subacute toxicity --- p.43 / Chapter 2.2.3.4 --- Reproductive toxicity --- p.44 / Chapter 2.2.4 --- Statistical analysis --- p.44 / Chapter Chapter Three: --- Results / Chapter 3.1 --- Immunomodulatory effects of Mimosa pudica / Chapter 3.1.1 --- In vitro study on the lymphocyte proliferation / Chapter 3.1.1.1 --- Splenocyte proliferation --- p.45 / Chapter 3.1.1.2 --- Thymocyte proliferation --- p.50 / Chapter 3.1.2 --- In vivo study on the lymphocyte proliferation --- p.53 / Chapter 3.1.3 --- Phagocytic activity of macrophages --- p.58 / Chapter 3.1.4 --- Release of IL-1 by macrophages --- p.64 / Chapter 3.1.5 --- Plaque forming cells --- p.67 / Chapter 3.1.6 --- Restoration on splenocyte blastogenesis of old mice --- p.69 / Chapter 3.2 --- Toxicity of Mimosa pudica / Chapter 3.2.1 --- LD50 --- p.72 / Chapter 3.2.2 --- Enzyme assays --- p.75 / Chapter 3.2.3 --- Subacute toxicity --- p.80 / Chapter 3.2.4 --- Reproductive toxicity --- p.85 / Chapter Chapter Four: --- General discussion on the immunomodulatory effects and toxicity of Mimosa pudica / Chapter 4.1 --- Immunomodulatory effects of Mimosa pudica --- p.88 / Chapter 4.2 --- Toxicity of Mimosa pudica --- p.95 / Chapter Chapter Five: --- Concluding remarks --- p.99 / References --- p.104 / Appendix --- p.113

Angus Chun-tim Lo. / Thesis (M. Phil.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 138-147). / ACKNOWLEDGEMENTS --- p.i / LIST OF PUBLICATIONS --- p.ii / ABSTRACT --- p.iii / ABBREVIATIONS --- p.viii / Chapter CHAPTER 1 --- General Introduction --- p.1 / Chapter CHAPTER 2 --- The Effects of Danshen (Salvia miltiorrhiza) on Pharmacokinetics and Pharmacodynamics of Warfarin / Chapter 2.1 --- Introduction --- p.35 / Chapter 2.2 --- Materials and Methods --- p.42 / Chapter 2.3 --- Results --- p.54 / Chapter 2.4 --- Discussion --- p.64 / Chapter CHAPTER 3 --- The Effects of Danshen (Salvia miltiorrhiza) on Pharmacological Properties of the Stereoisomers of Warfarin / Chapter 3.1 --- Introduction --- p.68 / Chapter 3.2 --- Materials and Methods --- p.72 / Chapter 3.3 --- Results --- p.84 / Chapter 3.4 --- Discussion --- p.99 / Chapter CHAPTER 4 --- The Effects of Danggui (Angelica sinensis) on Pharmacokinetics and Pharmacodynamics of Warfarin / Chapter 4.1 --- Introduction --- p.104 / Chapter 4.2 --- Materials and Methods --- p.114 / Chapter 4.3 --- Results --- p.120 / Chapter 4.4 --- Discussion --- p.127 / Chapter CHAPTER 5 --- General Conclusion --- p.131 / REFERENCES --- p.138

Chen Feng. / "August 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 166-178). / 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.

by Zhao Xin. / "October 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 235-260) / 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.

Mak Chun-yin. / "February 2001." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 156-169). / 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.

Metabolic syndrome refers to clusters of risk factors (e.g. obesity, hyperlipidemia, insulin resistance, non-alcoholic fatty liver and hypertension) that would lead to development of cardiovascular disease. The prevalence of this disease is high and the therapeutic approaches are insufficient. Potential use of Chinese herbal medicines to target on metabolic syndrome has attracted great attention. Erigerontis Herba (EH) is a Chinese herb that is traditionally used to treat cardiovascular and cerebrovascular diseases. Its effect on diet-induced metabolic syndrome has not been previously investigated. The present study was the first investigation of the effects of Erigerontis Herba, Erigerontis containing herbal formulae and its polyphenol-enriched fraction (EHP) on diet-induced metabolic syndrome. / To determine the effects of EH, EH-containing herbal formulae and EHP on obesity, hyperlipidemia, hepatic steatosis and hypertension, in vitro, ex vivo and in vivo models were used. For in vitro studies, cholesterol uptake inhibition and adipogenesis differentiation assays were performed using Caco-2 cells and 3T3-L1 adipocytes, respectively. Ex vivo organ bath studies were performed to determine the vasodilative effects, and respective underlying mechanisms were determined via inhibition of different pathways using corresponding blockers. In vivo animal model of high-fat diet-induced metabolic syndrome was performed using C57Bl/6 mice. Preventive effects of these herbal extracts were determined by supplementation of extract to high-fat diet for 8 weeks, followed by measurement of body weight, liver and adipose tissues weight, plasma lipid, plasma glucose and liver lipid. Proteins and genes expressions related to lipid metabolism were also determined using Western blotting and RT-PCR. Bioavailability of these herbal extracts were investigated using human intestinal Caco-2 cells monolayer. / Among all tested, EHP demonstrated most prominent effects in the inhibition of both cholesterol uptake and adipogenesis in vitro; and possessed significant vasodilative effects ex vivo, and also significant beneficial effects on obesity and hepatic steatosis in mice, but not on hyperlipidemia. EH-containing herbal formulae exhibited significant inhibitory effects on cholesterol uptake in Caco-2 cells. Among all tested, only DZ4 showed inhibitory effect on adipogenesis. EH, on the other hand, significantly inhibited adipogenesis but exerted no effect on cholesterol uptake. EH and EH-containing herbal formulae showed significant vasodilative effects in ex vivo studies. For in vivo studies, only DZ6 showed mild beneficial effects on diet-induced obesity (inguinal fat/body weight and peri-renal fat/body weight), hepatic steatosis and hyperlipidemia. EH alone showed no significant beneficial effects on high-fat diet-induced metabolic syndrome in mice. Preliminary bioavailability experiments suggested that all herbal preparations had relatively low bioavailability, although EHP had a comparative higher permeation ability through Caco-2 monolayer. / In conclusion, this is the first comprehensive study of the effects of EH (with or without other herbs) on diet-induced metabolic syndrome. EHP, a polyphenol-enriched fraction isolated from EH showed potent beneficial effect on diet-induced obesity and hepatic steatosis both in vitro and in vivo, as well as significant vasodilative effects ex vivo. These data suggested the potential for EHP to be developed as dietary supplementation for metabolic syndrome. The effects will be further determined in clinical trials in the future. / 代謝綜合癥是多種心血管危險因子異常聚集的病理狀態，其病癥包括肥胖，高血脂，胰岛素抗性，高血糖，脂肪肝和高血壓等。它的發病率很高，但是目前治療以及預防這一疾病的措施尚不完善。近年來，用中藥治疗這一疾病引起人们廣大關注。燈盞細辛作為傳統中草藥經常用於心血管和腦血管疾病，但其對於代謝綜合癥是否有效有待研究發現。本課題組建立了高脂餵食引起代謝綜合癥模型，并探討了燈盞細辛，燈盞細辛複方，以及燈盞細辛你酚類對此疾病的療效及作用機制。 / 我們用體內，體外及離體模型研究了燈盞細辛，燈盞細辛複方以及燈盞細辛酚對於肥胖，高血脂，脂肪肝和高血壓的作用。我們用3T3-L1和Caco-2細胞模型研究了燈盞細辛相關提取物對於膽固醇吸收和脂肪生成的作用，用大鼠離體血管環體外實驗，研究了他們對於血管擴張的作用及其機制。另外，本課題組建立了高脂餵食小鼠代謝綜合癥模型，并探討了這些中藥提取物作為食物補充劑對於代謝綜合癥的作用。我們用實時定量PCR技術和蛋白質印跡技術測量了各種相關蛋白和基因的表達。此外，我們還用人的腸細胞單層轉運模型研究了這些中藥提取物的生物利用度。 / 體外實驗結果表明，四個燈盞細辛複方都有明顯抑制膽固醇吸收的作用，但是對於脂肪生成，只有複方DZ4有明顯抑制作用。燈盞細辛提取物可以明顯抑制脂肪生成，但是對膽固醇吸收卻沒有明顯作用。燈盞細辛酚對於兩者都具有明顯的抑制作用。另外，大鼠離體動血管環研究結果顯示，燈盞細辛複方，燈盞細辛提取物以及燈盞細辛酚都有明顯的擴張血管的作用。高脂餵食小鼠代謝綜合癥實驗結果結果顯示四個燈盞細辛複方中只有複方DZ6對於肥胖，脂肪肝和高血脂有作用。燈盞細辛對代謝綜合癥無明顯作用，但是燈盞細辛酚對于肥胖和脂肪肝卻有明顯抑制作用對於此代謝綜合癥小鼠模型。生物利用度相關研究結果顯示，燈盞細辛，燈盞細辛複方以及燈盞細辛酚的生物利用度都相對較低。 / 總括來說，我們綜合研究了燈盞細辛對於代謝綜合癥的藥效。燈盞細辛酚對於肥胖和脂肪肝在體內體外模型都顯示了較好的抑製作用。再加上其對於擴張血管有非常明顯的作用，它有潛能被發展為代謝綜合癥的治療預防方法。 / Wang, Yanping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 243-256). / Abstracts also in Chinese. / Title from PDF title page (viewed on 01, November, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

by Wing Shun Cheung. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 159-178). / 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.