Natural Abilities Are Like Natural Plants, That Need Pruning by Study” by Bacon, Francis
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“Natural abilities are like natural plants, that need pruning by study” by Bacon, Francis Members of the jury 1. Prof. Yue Dai, Department of Pharmacognosy of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, China 2. Prof. Dr. ir. Norbert De Kimpe, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Belgium (promoter) Prof. Zheng-tao Wang, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, China (promoter) 3. Prof. Dr. Stefaan De Smet, Department of Animal Production, Faculty of Bioscience Engineering, Ghent University, Belgium 4. Prof. Dr. Tom Desmet, Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Belgium 5. Prof. Ling-yi Kong, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, China 6. Prof. Jian-xin Li, Department of Organic Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, China 7. Prof. Wei-lin Li, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, China 8. Prof. Bo-yang Yu, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, China Promoters: Prof. Dr. ir. Norbert De Kimpe Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University Prof. Zheng-Tao Wang Department of Pharmacognosy, China Pharmaceutical University Dean: Prof. Dr. ir. Guido Van Huylenbroeck Rector: Prof. Dr. Paul Van Cauwenberge MSc. Jian Chen STUDY ON THE ISOLATION, CHARACTERIZATION AND POSSIBLE BIOACTIVITY OF CONSTITUENTS WITH HYPOGLYCEMIC ACTIVITY FROM GYNURA DIVARICATA AND G. BICOLOR Thesis submitted in fulfillment of the requirements for the degree of Doctor (PhD) in Applied Biological Sciences: Chemistry Dutch translation of the title: Studie van de isolatie, karakterisering en mogelijke bioactiviteit van bestanddelen met hypoglycemische activiteit van Gynura divaricata en G. bicolor. To refer to this thesis: Jian Chen (2013). Study on the isolation, characterization and possible bioactivity of constituents with hypoglycemic activity from Gynura divaricata and G. bicolor. Doctoral dissertation, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium. ISBN-number: 978-90-5989-604-8 The author and the promoter give the authorisation to consult and to copy parts of this work for personal use only. Every other use is subject to the copyright laws. Permission to reproduce any material contained in this work should be obtained from the author Ghent, April 2013 The author, The promoter, The promoter, MSc. Jian Chen Prof. Dr. ir. Norbert De Kimpe Prof. Zheng-Tao Wang This research was made possible by a scholarship of the Special Research Fund of Ghent University, Ghent, Belgium (BOF-UGent). Part of this research was financed by the National Natural Science Foundation of China (No. 30900123) and a grant from Jiangsu Center for Research & Development of Medicinal Plants, Nanjing (No. 200902). Preface Upon the termination of my Ph.D. thesis, I would like to take this opportunity to express my sincere gratitude, from my heart, to all the individual persons who have contributed to the completion of this work. First of all, I deeply appreciate my promoter, Prof. Dr. ir. Norbert De Kimpe for the opportunity he offered me to study in Ghent University and his supervision and critical review throughout the course of my doctoral research work. I still remember the first time we met in Nanjing in June 2005, and until now we have worked together for a long time. I am grateful to him for sharing with me the serious way to do the science, which I will keep in mind at my academic career in the future. I also would like to thank my promoter Prof. Zheng-Tao Wang, for his guidance and sharing knowledge on the isolation of natural products. Even I was abroad, he would discuss with me on the thesis for hours by phone. I am very thankful to him. Their supervision, criticism and encouragement were so important to me that I definitely could not complete this work without them. With all respect and gratitude, I refer to Prof. Wei-Lin Li, the vice rector of the Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, for having played a key role of the admission at Ghent University. His research group had a very nice collaboration with that of Prof. N. De Kimpe on natural products and he introduced me to Prof. N. De Kimpe after my stay in the institute. I would like to thank Dr. ir. Sven Mangelinckx and Dr. ir. An Adams, who guided me when I was in Ghent. Thanks a lot for sharing their high level scientific skills. I am very grateful for their help on the purification and characterization of natural products, as well as the corrections on all the paper work. The stay together with them was beneficial to me from the technical for science and the virtue for human being. Special thanks also go to Dr. ir. Pieter Zwaenepoel, for his kind assistance on the Mass and HPLC analysis during my stay in UGent. Also the scientific contribution from Dr. Li Ma from the Institute of Botany, Jiangsu Province and Chinese Academy of Sciences on the bio-testing work was much appreciated. I would also like to thank Dr. Ai-Zhen Xiong from Shanghai University of Traditional Chinese Medicine for her good collaboration in taking the necessary LC-MS spectra. I am highly grateful to the Special Research Fund (BOF-UGent) for an eighteen-months financial support for my stay in Ghent. Funds and support were also provided by the National Natural Science Foundation of China (No. 30900123) and a project from Jiangsu Center for Research & Development of Medicinal Plants (No. 200902). These support let me more focus on the research work, getting rid of the concern of living cost. I would like to thank the members of the reading committee: 1. Prof. Dr. Tom Desmet, Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Belgium 2. Prof. Ling-yi Kong, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, China 3. Prof. Jian-xin Li, Department of Organic Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, China for their critical evaluation of my thesis. There are so many people outside of my research who encouraged me, it’s too many to mention. I want to thank all the colleagues in the Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, as well as the colleagues in the Institute of Botany, Jiangsu Province and Chinese Academy of Sciences for the wonderful atmosphere and good memory we shared during these years. No words can describe my gratitude to my wife Windy. She sacrificed a lot during these years because I was always away from home. Her understanding, tolerance, love and endless encouragement always support me to continue the doctoral work. I dedicated this work to you because I couldn’t have accomplished it without you. Last but not the least, I would not forget to thank my dear parents. You are an inspiration for me to be a strong man, a real father. And I have learned from you what is responsibility. My little son Yilin, although not yet old enough to understand what I am writing right now, I want to say sorry to you because I owed you a complete childhood when I was abroad. I wish I can make complement to you in the rest of our life. Should there be anyone I failed to acknowledge, my sincere regret, my apology and my thanks go to him / her too. Jian April, 2013 Table of contents Chapter 1 General Introduction....................................................................................... 1 1.1 Natural products.................................................................................................. 2 1.2 Genus Gynura and overview of compounds isolated from Gynura Cass.............. 5 1.2.1 Description of the genus Gynura...….......................................................... 5 1.2.2 Phytochemical investigation of plant species from the genus Gynura…..... 6 1.3 Natural flavonoids as potential herbal medication for the treatment of diabetes mellitus and its complications.............................................................. 16 1.3.1 Introduction............................................................................................... 16 1.3.2 Mechanisms of action of natural flavonoids for the treatment of diabetes mellitus....................................................................................... 18 1.3.2.1 Action on islet β-cells and release of insulin from β-cells................... 18 1.3.2.2 Enhancement of glucose utilization in tissues and organs.................. 19 1.3.2.3 Reduction of breakdown of glycogen................................................. 19 1.3.2.4 Inhibition of α-glucosidase to reduce intestinal glucose absorption.......................................................................................... 19 1.3.2.5 Antioxidant free radical scavenging activity........................................ 20 1.3.2.6 Inhibition of AGE formation and AGE-mediated damage................... 20 1.3.3 Natural flavonoids with antidiabetic activities reported from in vivo studies....................................................................................................... 29 1.3.4 Studies on flavonoids used for the