Li Mi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 125-136). / Abstracts in English and Chinese. / Abstract --- p.i / 論文摘要 --- p.iv / Publications --- p.vi / Acknowledgement --- p.vii / Abbreviations --- p.viii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Pyrrolizidine alkaloids --- p.1 / Chapter 1.1.1 --- Distribution and plant sources --- p.1 / Chapter 1.1.2 --- Structures and nomenclature --- p.3 / Chapter 1.2 --- PA-containing Chinese medicinal herbs --- p.6 / Chapter 1.3 --- PA-induced toxicity。 --- p.7 / Chapter 1.3.1 --- Acute toxicity and chronic toxicity --- p.7 / Chapter 1.3.2 --- Genotoxicity --- p.8 / Chapter 1.3.3 --- Tumorigenicity --- p.8 / Chapter 1.3.4 --- Hepatotoxicity --- p.8 / Chapter 1.3.5 --- Mechanism of toxic effects --- p.9 / Chapter 1.3.5.1 --- Metabolic pathways --- p.10 / Chapter 1.3.5.2 --- Liver tissue-bound pyrroles --- p.16 / Chapter 1.3.5.3 --- Metabolizing enzymes --- p.17 / Chapter 1.3.5.3.1 --- Phase I metabolizing enzymes --- p.17 / Chapter 1.3.5.3.2 --- Phase II metabolizing enzymes --- p.18 / Chapter 1.3.5.4 --- Species and gender specificity toward toxicity --- p.19 / Chapter 1.3.5.5 --- Structure-activity relationships --- p.20 / Chapter 1.4 --- Prevention of PAs-induced toxicity --- p.23 / Chapter 1.4.1 --- Significance of prevention in humans --- p.23 / Chapter 1.4.2 --- Regulations toward preventing toxicity induced by PAs --- p.24 / Chapter 1.5 --- Aim of the present study --- p.25 / Chapter Chapter 2 --- Qualitative and Quantitative Analysis of PA-containing Chinese Medicinal Herbs --- p.26 / Chapter 2.1 --- Materials and equipments --- p.27 / Chapter 2.1.1 --- Herbal materials --- p.27 / Chapter 2.1.2 --- Chemicals and solvents --- p.27 / Chapter 2.1.3 --- Equipment and instrumentation --- p.27 / Chapter 2.2 --- Preparation of herbal extracts。 --- p.28 / Chapter 2.2.1 --- Crude herbal extract --- p.28 / Chapter 2.2.2 --- Total pyrrolizidine alkaloid extract --- p.28 / Chapter 2.3 --- Qualitative and quantitative analysis of Ligularia hodgsonii --- p.29 / Chapter 2.3.1 --- Methods --- p.29 / Chapter 2.3.1.1 --- HPLC-UV condition --- p.29 / Chapter 2.3.1.2 --- HPLC-MS condition --- p.29 / Chapter 2.3.1.3 --- Calibration curve for clivorine --- p.29 / Chapter 2.3.1.4 --- Recovery test --- p.30 / Chapter 2.3.1.5 --- Sample test --- p.30 / Chapter 2.3.2 --- Results and discussions --- p.30 / Chapter 2.3.2.1 --- Qualitative analysis of PAs in Ligularia hodgsonii --- p.30 / Chapter 2.3.2.2 --- Calibration curve for clivorine --- p.35 / Chapter 2.3.2.3 --- Result of the recovery test --- p.37 / Chapter 2.3.2.4 --- Quantification of PAs in Ligularia hodgsonii --- p.37 / Chapter 2.4 --- Qualitative and quantitative analysis of Tussilago farfara --- p.37 / Chapter 2.4.1 --- Methods --- p.38 / Chapter 2.4.1.1 --- HPLC-UV condition --- p.38 / Chapter 2.4.1.2 --- HPLC-MS condition --- p.39 / Chapter 2.4.1.3 --- Calibration curve for senkirkine --- p.39 / Chapter 2.4.1.4 --- Recovery test --- p.39 / Chapter 2.4.1.5 --- Sample test --- p.39 / Chapter 2.4.2 --- Results and discussions --- p.40 / Chapter 2.4.2.1 --- Qualitative analysis of senkirkine in Tussilago farfara --- p.40 / Chapter 2.4.2.2 --- Calibration curve for senkirkine --- p.42 / Chapter 2.4.2.3 --- Result of the recovery test --- p.42 / Chapter 2.4.2.4 --- Quantification of senkirkine in Tussilago farfara --- p.43 / Chapter 2.5 --- Qualitative and quantitative analysis of Gynura segetum --- p.43 / Chapter 2.5.1 --- Methods --- p.43 / Chapter 2.5.1.1 --- HPLC-UV condition --- p.43 / Chapter 2.5.1.2 --- HPLC-MS condition --- p.44 / Chapter 2.5.1.3 --- Calibration curves for senecionine and seneciphylline --- p.44 / Chapter 2.5.1.4 --- Recovery test… --- p.44 / Chapter 2.5.1.5 --- Sample test --- p.44 / Chapter 2.5.2 --- Results and discussions。 --- p.45 / Chapter 2.5.2.1 --- Qualitative analysis of PAs in Gynura segetum --- p.45 / Chapter 2.5.2.2 --- Calibration curves for senecionine and seneciphylline --- p.49 / Chapter 2.5.2.3 --- Result of the recovery test --- p.49 / Chapter 2.5.2.4 --- Quantification of PAs in Gynura segetum --- p.49 / Chapter 2.6 --- Qualitative and quantitative analysis of Crotalaria sessiliflora --- p.50 / Chapter 2.6.1 --- Methods --- p.50 / Chapter 2.6.1.1 --- HPLC-UV condition --- p.50 / Chapter 2.6.1.2 --- HPLC-MS condition --- p.50 / Chapter 2.6.1.3 --- Calibration curve --- p.51 / Chapter 2.6.1.4 --- Recovery test --- p.51 / Chapter 2.6.1.5 --- Sample test --- p.51 / Chapter 2.6.2 --- Results and discussions --- p.52 / Chapter 2.6.2.1 --- Qualitative analysis of monocrotaline in Crotalaria sessiliflora --- p.52 / Chapter 2.6.2.2 --- Calibration curve for monocrotaline --- p.54 / Chapter 2.6.2.3 --- Result of the recovery test --- p.54 / Chapter 2.6.2.4 --- Quantification of PAs in Crotalaria sessiliflora --- p.55 / Chapter 2.7 --- Qualitative and quantitative analysis of Senecio scandens --- p.55 / Chapter 2.7.1 --- Methods --- p.55 / Chapter 2.7.1.1 --- HPLC-UV condition --- p.55 / Chapter 2.7.1.2 --- HPLC-MS condition --- p.56 / Chapter 2.7.1.3 --- Sample test --- p.56 / Chapter 2.7.2 --- Results and discussions --- p.56 / Chapter 2.7.2.1 --- Qualitative analysis of PAs in Senecio scandens --- p.56 / Chapter 2.7.2.2 --- Quantification of PAs in Senecio scandens --- p.59 / Chapter Chapter 3 --- Hepatotoxicity Induced by PA-containing Chinese Medicinal Herbs --- p.60 / Chapter 3.1 --- Materials and methods --- p.62 / Chapter 3.1.1 --- Reagents --- p.62 / Chapter 3.1.2 --- Animal models --- p.62 / Chapter 3.1.3 --- Determination of the serum ALT activity --- p.64 / Chapter 3.1.4 --- Determination of hepatic GSH level --- p.68 / Chapter 3.1.5 --- Quantitation of liver tissue-bound pyrroles --- p.69 / Chapter 3.1.6 --- Histological assessment of liver morphological changes --- p.70 / Chapter 3.1.7 --- Assessment of hepatocytes apoptosis --- p.71 / Chapter 3.1.8 --- Statistical analysis --- p.72 / Chapter 3.2 --- Results and discussion --- p.72 / Chapter 3.2.1 --- Calibration curves --- p.72 / Chapter 3.2.1.1 --- Calibration curve for the determination of serum ALT activity --- p.72 / Chapter 3.2.1.2 --- Calibration curve of determination of hepatic GSH level --- p.73 / Chapter 3.2.2 --- Hepatotoxicity Study of Crotalaria sessiliflora --- p.74 / Chapter 3.2.2.1 --- Hepatotoxicity at 24 hrs after treatment --- p.74 / Chapter 3.2.2.1.1 --- Correlation between dosage of monocrotaline in Crotalaria sessiliflora and amount of liver tissue-bound pyrroles --- p.74 / Chapter 3.2.2.1.2 --- Effects of Crotalaria sessiliflora on the serum ALT activity --- p.79 / Chapter 3.2.2.1.3 --- The correlation between the elevated level of ALT activity and apoptosis of liver cells --- p.85 / Chapter 3.2.2.1.4 --- Effects of Crotalaria sessiliflora on the hepatic GSH level --- p.86 / Chapter 3.2.2.1.5 --- Histological changes of liver sections --- p.89 / Chapter 3.2.2.2 --- Hepatotoxicity within 4 days after administration --- p.92 / Chapter 3.2.2.3 --- Sub-acute hepatotoxicity within 14 days after administration --- p.93 / Chapter 3.2.2.4 --- Conclusion in hepatotoxicity study of Crotalaria sessiliflora --- p.99 / Chapter 3.2.3 --- Hepatotoxicity Study of Gynura segetum --- p.102 / Chapter 3.2.3.1 --- Correlation between the dosage of PAs present in Gynura segetum and the amount of liver tissue-bound pyrroles --- p.102 / Chapter 3.2.3.2 --- "Effects of Gynura segetum on serum ALT activity, hepatic GSH level and morphological changes of liver" --- p.104 / Chapter 3.2.4 --- Hepatotoxicity Study of Ligularia hodgsonii --- p.108 / Chapter 3.2.4.1 --- Correlation between the dosage of PAs present in Ligularia hodgsonii and the formation of liver tissue-bound pyrroles --- p.108 / Chapter 3.2.4.2 --- Effects of Ligularia hodgsonii on serum ALT activity and hepatic GSH level --- p.111 / Chapter 3.2.5 --- Hepatotoxicity Study of Tussilago farfara --- p.113 / Chapter 3.2.6 --- Hepatotoxicity Study of PA-containing medicinal herbs --- p.115 / Chapter 3.2.6.1 --- Correlation between formation of liver tissue-bound pyrroles and elevated serum ALT level --- p.115 / Chapter 3.2.6.2 --- Correlation between dosage of PAs and amount of liver tissue-bound pyrroles --- p.117 / Chapter 3.2.7 --- Test of Liver Tissue-bound Pyrroles as a biomarker using Senecionis scandentis --- p.118 / Chapter 3.2.8 --- Conclusions --- p.120 / Chapter Chapter 4 --- General Conclusions --- p.121 / Chapter 4.1 --- Qualitative and quantitative analysis of five PA-containing medicinal herbs --- p.121 / Chapter 4.2 --- Hepatotoxicity induced by PA-containing medicinal herbs in rats --- p.122 / Chapter 4.3 --- The correlation between hepatotoxicity induced by PA-containing medicinal herbs and the formation of liver tissue-bound pyrroles --- p.123 / Chapter 4.4 --- Threshold of the amount of liver tissue-bound pyrroles related to the hepatotoxicity induced by PA-containing medicinal herbs --- p.123 / References --- p.125
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_326541 |
| Date | January 2008 |
| Contributors | Li, Mi., Chinese University of Hong Kong Graduate School. Division of Pharmacology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | print, xiii, 136 leaves : ill. (some col.) ; 30 cm. |
| Coverage | China, China |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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