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.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343859 |
| Date | January 2005 |
| Contributors | Yan, Ru, 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, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xvii, 275 : ill.) |
| Coverage | 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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