Different cucurbitacin derivatives have been compared for the gamma globin induction potential. Cucurbitacin D turned out to be the most potential inducer among the derivatives had been tested. Later I had screened more herbs for the gamma globin induction activities. One of the herbs showed a higher activity than Fructus Trichosanthis, which could be the potential candidate to isolate more potent inducer. In the toxicity study, cucurbitacin D only have a mild toxic effect on the normal cell lines and transgenic mice. Finally, the efficacy of cucurbitacin D was tested on a sickle cell anemia mouse model and demonstrated a significant induction of fetal haemoglobin production. Cucurbitacin D may be a potential drug candidate for treating beta globinopathies. / Thalassemia is a global disease. It was report in 2001 that there were 270 million people who carried the severe disease. Most of the cases were found in Africa and south-east Asia. China has a high incidence rate of 0.66% in 2001. In the past, the treatments of the disease were blood transfusion and bone marrow transplantation. However, many defects in such kinds of treatments were reported. The balance of relieving the syndrome of the disease and the adverse effects of the drugs was the consideration to the physician. The drug, hydroxyurea, can activate the gamma globin gene and produce hemoglobin F to replace the beta globin as an oxygen transporter is considered as an better treatment to ameliorate the syndrome. Safety and effectiveness in the long-term treatment using hydroxyurea are questionable. Cucurbatacin D purified from a Chinese herb demonstrates 2000 folds more potent than hydroxyurea. It can activate the gamma globin gene and produce hemoglobin F shown in ELISA and confocal microscopy. The fundamental work for drug development is carrying out through this project. In this project the biological property and toxicity were studied. / Liu, Shuk Ming. / Adviser: M.C. Tung. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 245-270). / 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.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344710 |
| Date | January 2010 |
| Contributors | Liu, Shuk Ming., Chinese University of Hong Kong Graduate School. Division of Life Sciences. |
| 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 (xviii, 270 leaves : ill.) |
| 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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