- UNIVERSITY OF NAIROBI CHEMOSYSTEMATICS, ANTIMICROBIAL AND ANTIPROLIFERATIVE ACTIVITIES OF THE KENYAN ZANTHOXYLUM SPECIES AND DODONAEA VISCOSA POPULATIONS BY KAIGONGI MUTHONI MAGRATE BSc (1st Class Honors), MSc (University of Nairobi) (REG. NO. I80/52651/2018) A Thesis Submitted in Fulfillment of the Requirements for Award of the Degree of Doctor of Philosophy in Plant Taxonomy and Economic Botany in the School of Biological Sciences, University of Nairobi 2020 ii DEDICATION This thesis is dedicated to my dear husband Dr. Fredrick Musila and children Ethan and Noreen in gratitude for their patience, sacrifices and support they accorded to me during this study. Their sacrifice gave me the much needed moral support to pursue this study. iii ACKNOWLEDGEMENTS I am sincerely grateful to The Lord Almighty for the good health, zeal and sufficient grace that He accorded to me during this study. I am also indebted to my supervisors, Dr. Catherine Lukhoba and Prof Abiy Yenesew for their tireless continued intellectual guidance and moral support and for going an extra mile to fund my research amongst many students. In fact, the love you have shown me during this study is like that of parents to their children, may God bless you abundantly. Appreciation goes to Prof. Nox Makunga of Stellenbosch University for not only hosting me in South Africa during the chemosystematics study but also guiding me on the metabolomics objective which is part of this study. Many thanks to Ms. Mizpah Hoffman, Mr. Jan Marx, Mr. Taylor, Dr. Stander and Dr. Jaco Brand all from Stellenbosch University for their guidance and carrying out the LC-MS analysis for my samples. Special thanks goes to Dr. Mathias Heydenreich of University of Potsdam, Germany for carrying out the NMR analysis of the isolated compounds. Dr. Peter Mwitari and Regina Mbugua of Centre for Traditional Medicinal and Drug Research (CTMDR), Kenya Medcal Research Institute (KEMRI) are sincerely appreciated for their assistance in anticancer analysis. I am also grateful to Mr. Wachira and Ndii of Microbiology lab, School of Biological Sciences University of Nairobi for their unwaivering support during the antimicrobial study. More thanks go to Dr. Souaibou Yaouba for guiding me in isolation as well as description of compounds. I am grateful to my colleague students at Prof. Abiy’s lab, Carolyne Chepkurui, Douglas Ochora, Duncan Mutiso, Purity Achieng, Nicholus Mwanzia and Jeremiah for their support during the phytochemistry work. Special thanks to Purity and Jeremiah for teaching me basic spectroscopy skills. iv Many thanks to Kenya Forestry Research Institute (KEFRI) management and especially to Dr. Joram Kagombe the regional director, Central Highlands Ecoregion Research Program (CHERP), for allowing me to work on this study alongside my other duties as an employee of the institute. Dr. Jane Njuguna, Dr. Beryn Otieno, Dr. Mercy Gichora, Dr. Stephen Omondi, Ms. Betty-Prissy Njoki and other colleagues from KEFRI are appreciated for their moral support and understanding they have shown through out this study. I am greatly indebted to my dear husband Dr. Fredrick Musila for the sacrifices and support both financially and morally that he has made during this study. Always making sure that our children, Ethan and Noreen were well taken care of and always ensuring that this study was running as it ought to be. To my children, thank you for understanding that I have been a student especially during the write up of the thesis when you believed that mummy was ‘writing her final exams’ and thus did not require disturbances! Thanks to my siblings who have always believed in me, to my sister Lucy Mutegi, you are not only a sister but also a confidant, always listening and caring. To my brother in law, Harrison Mati, I owe all my academic success to you as you are the person who first brought me to the university for my undergraduate studies where the journey began. I also appreciate my parents, my dad Stanley Mutegi whose love for academics is undisputable and my mum Severinah Magane, though you rested when I was aged 5 years, stories of your hardwork and generosity are still fresh in the community and have always encouraged me to work hard in my studies.To those mentioned and not mentioned please feel appreciated and know that your kind gesture to me at one point in life will forever be remembered. v TABLE OF CONTENTS DEDICATION……………………………………………………………………………………………………….iii ACKNOWLEDGEMENTS ................................................................................................................................. iv TABLE OF CONTENTS .................................................................................................................................... vi LIST OF FIGURES .............................................................................................................................................. x LIST OF ACRONYMS ...................................................................................................................................... xii LIST OF APPENDICES ................................................................................................................................... xiii ABSTRACT ....................................................................................................................................................... xiv CHAPTER ONE ................................................................................................................................................... 1 GENERAL INTRODUCTION ............................................................................................................................ 1 1.1.Background information ............................................................................................................................... 1 1.2 Problem statement ........................................................................................................................................ 3 1.3. Justification ................................................................................................................................................. 4 1.4. Hypotheses .................................................................................................................................................. 5 1.5. Objective ..................................................................................................................................................... 6 1.5.1. General Objectives ............................................................................................................................... 6 1.5.2. Specific objectives ................................................................................................................................ 6 1.6.Relevance of the study .................................................................................................................................. 6 1.6.Thesis structure ............................................................................................................................................ 7 CHAPTER TWO: LITERATURE REVIEW...................................................................................................... 8 2.1. Use of medicinal plants of the world ............................................................................................................ 8 2.2. Chemotaxonomy as a tool for plants classification........................................................................................ 8 2.3. Bioactive phytochemicals ............................................................................................................................ 9 2.4. Antibiotic resistance .................................................................................................................................. 10 2.5. Cancer causes and development ................................................................................................................. 10 2.5.1. The burden of cancer disease to human health ..................................................................................... 11 2.5.2. Treatement methods of cancer and their downsides ............................................................................. 12 2.6. Plants used medicinally in Kenya ............................................................................................................... 13 2.7 Order Sapindales ........................................................................................................................................ 14 2.7.1 The family Rutaceae Juss. .................................................................................................................... 14 2.7.2. The genus Zanthoxylum L. .................................................................................................................. 15 2.7. 3. Taxonomic treatment of Zanthoxylum and some challenges encountered ............................................ 17 2.7.4. Description of Zanthoxylum species found in Kenya............................................................................ 18 2.9. The family Sapindaceae Juss. ..................................................................................................................... 22 2.10. Taxonomic treatment of the genus Dodonaea L. ....................................................................................... 22 2.10.1. Morphology, medicinal uses and phytochemistry of Dodonaea