MODERN TOOLS TO STUDY TRADITIONAL MEDICINAL PLANTS:GINGER AND TURMERIC Item Type text; Electronic Dissertation Authors Jiang, Hongliang Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 28/09/2021 01:50:16 Link to Item http://hdl.handle.net/10150/193562 MODERN TOOLS TO STUDY TRADITIONAL MEDICINAL PLANTS: GINGER AND TURMERIC by Hongliang Jiang _____________________ A Dissertation Submitted to the Faculty of the DEPARTMENT OF PHARMACEUTICAL SCIENCES In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2005 2 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Dissertation Committee, we certify that we have read the dissertation prepared by Hongliang Jiang entitled Modern Tools to Study Traditional Medicinal Plants: Ginger and Turmeric and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy Barbara N. Timmermann, Ph.D. Date: 06/16/05 David R. Gang, Ph.D. Date: 06/16/05 Myron K. Jacobson, Ph.D. Date: 06/16/05 Victor J. Hruby, Ph.D. Date: 06/16/05 Danzhou Yang, Ph.D. Date: 06/16/05 Final approval and acceptance of this dissertation is contingent upon the candidate’s submission of the final copies of the dissertation to the Graduate College. I hereby certify that I have read this dissertation prepared under my direction and recommend that it be accepted as fulfilling the dissertation requirement. Dissertation Director: Barbara N. Timmermann Date: 06/16/05 David R. Gang Date: 06/16/05 3 STATEMENT BY AUTHOR This dissertation has been submitted in partial fulfillment of requirements for an advanced degree at The University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this dissertation are allowable without special permission, provided that accurate acknowledgment of source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgment the proposed use of the material is in the interests of scholarship. In all other instances, however, permission must be obtained from the author. SIGNED: Hongliang Jiang 4 ACKNOWLEDGEMENTS I would like to thank Drs. Barbara N. Timmermann and David R. Gang for their support and guidance for my research and for the enormous help and effect they have had on my life and scientific attitude. In addition, I thank them for their encouragement, patience, and confidence right from the beginning of my research. I would also like to thank Drs. Myron K. Jacobson, Victor J. Hruby, and Danzhou Yang for their teaching, advice, consultations, corrections, and generous help that have been critical to this work and my career planning. My thanks go out to Dr. Arpad Somogyi for his extremely helpful consultations and discussions about mass spectrometry and for providing an excellent resource for part of the work in this study. I also want to thank Dr. Neil Jacobsen for his teaching about the theory and application of NMR and assistance in its operation. My appreciation also goes out to Dr. Aniko Solyom and Veronica Rodriguez for their generous help in my use of their HPLC and LC-MS and discussion about the results obtained. Moreover, I want thank Dr. Guanjie Chen for his help with the anti- inflammatory bioassay, Dr. Yeisoo Yu for his help with DNA sequencing, Dr. Steven McLaughlin for plant material identification, as well as Jeffrey C. Oliver for consultation of phylogenetic analyses included in this study. I would also like to thank the past and present members of Dr. Gang’s laboratory. My thanks to Zhengzhi Xie and Hyun Jo Koo for their help with the DNA and secondary metabolites extraction, to Brenda L. Jackson for her assistance in instrumental operation, to Eric McDowell for revision of manuscript, and to Drs. Xiaoqiang Ma, Marycarmen Ramirez, Jeremy Kapteyn, Jennifer Wing and fellow students Shirley Chai and Amanda Scholz. Finally, I want to thank my parents Zonglu Jiang and Xiulian Li for their love, support, and encouragement throughout my growth. Moreover, I appreciate the help I received from my sister Hongmei Jiang in many aspects. Furthermore, I want to thank Yang Zhang for her love and care during this challenging time. Also, I want to thank all my friends for their general care, help, and confidence to me. This project is supported by the National Institutes of Health NCCAM/ODS, grants #5 P50 AT 000474-05 and 3 P50 AT 000474-03 S1 to B.N.T., and the National Science Foundation Plant Genome Program, grant DBI-0227618 to D.R.G. 5 TABLE OF CONTENTS LIST OF FIGURES…………………………………………………………………… 8 LIST OF TABLES……………………………………………………………………. 10 LIST OF SCHEMES………………………………………………………………….. 11 ABSTRACT...…………………………………………………………………………. 12 CHAPTER I − INTRODUCTION….………………………………………………… 14 1.1 Challenges and Opportunities for the Botanical Dietary Supplement Field…… 14 1.2 The Arizona Center for Phytomedicine Research (ACPRx)...………………… 16 1.3 A Brief Review of Ginger and Turmeric-Two Major Botanicals under Investigation at the ACPRx...………………………………………………… 17 1.3.1 Introduction……........................................................................................... 17 1.3.2 Ginger…...………………………………………………………………… 19 Historical and Current Uses and Clinical Studies of Ginger……...………… 19 Chemistry and Composition of Ginger……………………………………… 21 Analytical Techniques for Analysis of Ginger……………………………… 23 Phylogenetic Analysis of Ginger and Other Species in Genus Zingiber….… 24 Pharmacological Activities of Ginger……..………………………………… 24 Molecular Mechanisms of Anti-inflammatory Effects of Ginger…………… 25 Prospect of ginger as Anti-inflammatory Agents....………………………… 27 1.3.3 Turmeric…………………………………………………………………… 27 Historical and Current Uses and Clinical Studies of Turmeric……………… 27 Chemistry and Composition of Turmeric…………………………………… 29 6 TABLE OF CONTENTS − Continued Analytical Techniques for Analysis of Turmeric….………………………… 30 Phylogenetic Analysis of Turmeric and Other Species in Genus Curcuma … 31 Pharmacological Activities of Turmeric…..………………………………… 32 Molecular Mechanisms of Anti-inflammatory Effects of Turmeric ………… 33 Prospect of Curcumin as an Anti-inflammatory Agent……………...……… 34 1.4 Explanation of Thesis Format..………………………………………………… 35 CHAPTER II − PRESENT STUDY..………………………………………………… 38 2.1 General Methods Used for These Studies……………………………………… 38 2.1.1 Sample Preparation……...………………………………………………… 38 2.1.2 Standards Preparation…...………………………………………………… 39 2.1.3 GC/MS Analysis...………………………………………………………… 39 2.1.4 Quantitative Analysis of Gingerols by HPLC-DAD……………………… 40 2.1.5 HPLC-DAD-MS/MS Analysis….………………………………………… 41 LC Separation of Diarylheptanoid...………………………………………… 41 Diode Array Detection…….………………………………………………… 41 MS and MS2 Parameters for ThermoFinnigan LCQ Advantage….………… 41 MS and MS2 Parameters for Agilent LC-MSD-Trap-SL…………………… 42 2.1.6 Other Instrumentation…...………………………………………………… 42 2.2 DNA Sequence- and Chemical Character- Based Phylogenetic Analyses…..… 43 2.2.1 Phylogenetic Analysis of Ginger Accessions and Related Species..……… 44 2.2.2 Phylogenetic Analysis of Turmeric Accessions …………………….……. 52 7 TABLE OF CONTENTS − Continued 2.3 Identification of Compounds in Ginger and Turmeric…………………........… 58 2.3.1 Identification of Phenolics in Ginger..…………..………………………… 59 Identification of Gingerol Related Compounds in Ginger………………….. 60 Identification of Diarylheptanoids in Ginger……………………………….. 64 2.3.2 Identification of Compounds in Turmeric..….……………………………. 65 Identification of Diarylheptanoids from Turmeric…………………………. 66 Identification of Other Compounds from Turmeric………………………... 69 REFERENCES……..…………...……………………………………………………. 71 APPENDIX A……..…………...………………………………………….…………. 82 APPENDIX B……..…………...…………………………………………..………… 123 APPENDIX C……..…………...…………………………..…………………………. 164 APPENDIX D……..…………...…………………..…………………………………. 196 APPENDIX E……..…………...……………………..………………………………. 226 APPENDIX F……..…………...……………………..………………………………. 262 8 LIST OF FIGURES Figure 1.1. Some anti-inflammatory constituents in ginger rhizome………………… 22 Figure 1.2. Proposed anti-inflammatory mechanism of [6]-gingerol………………… 27 Figure 1.3. Some anti-inflammatory constituents in turmeric rhizome………………. 30 Figure 1.4. Proposed anti-inflammatory mechanism of curcumin……………………. 33 Figure 2.1. The experimental procedures for DNA sequence- and chemical character- based phylogenetic analysis……………………………………………… 44 Figure 2.2. Some sequence differences of Zingiber species and Alpinia galanga.…… 46 Figure 2.3. GC/MS profiles of different ginger accessions…………………………... 46 Figure 2.4. GC/MS profiles of different Zingiber species……………………………. 47 Figure 2.5. The content of gingerols in different ginger accessions………………….. 49 Figure 2.6. Comparison of phylogenetic trees of Zingiber species generated on the basis of DNA sequence and chemical characters………………………………. 50 Figure 2.7. Some sequence differences of turmeric accessions and Alpinia galangal... 53 Figure 2.8. GC/MS profiles of different turmeric accessions………………………… 53 Figure 2.9. The content of curcuminoids in different turmeric accessions……..…….