ANTIDIABETIC ACTIVITY AND SAFETY OF PIPER CAPENSE, BERBERIS HOLSTII, SONCHUS ASPER, VERNONIA LASIOPUS AND GALINSOGA PARVIFLORA IN ALLOXAN-INDUCED DIABETIC ALBINO MICE KIMANI LUCY NJERI (BSc) REG. NO.: 156/CE/26258/2011 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DEGREE OF MASTER OF SCIENCE IN MEDICAL BIOCHEMISTRY IN THE SCHOOL OF PURE AND APPLIED SCIENCE OF KENYATTA UNIVERSITY SEPTEMBER 2017 ii DECLARATION iii DEDICATION I dedicate this thesis to my husband Daniel Muraya and my daughter Nicole Wambui Muraya from whom I get inspiration. iv ACKNOWLEDGEMENT I am greatful to my supervisors Prof Eliud NM Njagi and Dr George O Orinda for their support and guidance as l carry out the project. I acknowledge the staff in the Department of Biochemistry and Biotechnology, Kenyatta University, for the support they offered. I thank Mr Chege Mwaura and Mr Kingo‟ri the traditional medical practitioners for the great contribution in collection of the medicinal herbs. Great thanks to Mr James Adino for technical assistance throughout the project. Sincere thanks to my parents Danson Kimani, Hellen Wambui and Ruth Wangari for their great contribution. Iam greatful to my family members Daniel Muraya, Nicole Wambui, Martha Waithera and Serah Wambui for their support through the entire period. I also thank my friends who all gave me courage and support. Above all, I give honour to the Almighty God for making everything possible. v TABLE OF CONTENT Page DECLARATION……………………………….…………………………………..ii DEDICATION .............................................................................................................. ii ACKNOWLEDGEMENT .......................................................................................... iv TABLE OF CONTENT ............................................................................................... v ABBREVIATIONS AND ACRONYMS ................................................................... ix LIST OF TABLES .................................................................................................... xiii ABSTRACT ............................................................................................................... xvi CHAPTER ONE........................................................................................................... 1 INTRODUCTION ........................................................................................................ 1 1.1 Background Information ....................................................................................... 1 1.2 Statement of the Research Problem and Justification of the study ................... 2 1.3 Research Hypotheses .............................................................................................. 4 1.4.1 General objective .................................................................................................. 4 1.4.2 Specific objectives ................................................................................................ 4 LITERATURE REVIEW ............................................................................................ 6 2.1 Diabetes ................................................................................................................... 6 2.2 Prevalence and Incidence of Diabetes Mellitus ................................................... 6 2.3 Signs and Symptoms .............................................................................................. 6 2.4 Types of Diabetes Mellitus..................................................................................... 7 2.4.1 Type I Diabetes Mellitus ....................................................................................... 7 2.4.2 Type II Diabetes Mellitus...................................................................................... 8 2.4.3 Gestational Diabetes.............................................................................................. 8 2.4.4 Other Specific Types of Diabetes ......................................................................... 8 2.4.5 Pre-diabetes ........................................................................................................... 8 2.5 Complications of Diabetes Mellitus ...................................................................... 9 2.5.1 Acute Complications of Diabetes Mellitus ........................................................... 9 2.5.1.1 Diabetic ketoacidosis (DKA) ............................................................................. 9 2 .5.1.2 Hyperosmolar non-ketotic coma ..................................................................... 10 2.5.1.3 Lactic acidosis (LA) ......................................................................................... 10 2.5.1.4 Hypoglycaemia ................................................................................................ 10 2.5.2 Chronic Complications of Diabetes Mellitus ...................................................... 10 2.5.2.1 Microvascular complications of diabetes ......................................................... 10 2.5.2.2 Macrovascular complications of diabetes ........................................................ 12 2.6 Causes Diabetes ................................................................................................... 14 2.6.1 Causes of Type I Diabetes................................................................................... 14 2.6.1.1 Autoimmune destruction of beta cells.............................................................. 14 2.6.1.2 Environmental factors ...................................................................................... 14 2.6.1.3 Infant Feeding Practices ................................................................................... 15 2.6.2 Causes of Diabetes Type II ................................................................................. 15 2.6.2.1 Genetic susceptibility ....................................................................................... 15 2.6.2.2 Obesity and physical inactivity ........................................................................ 15 2.6.2.3 Insulin resistance .............................................................................................. 16 vi 2.6.2.4 Abnormal glucose production by the liver ....................................................... 16 2.7 Diagnosis of Diabetes ........................................................................................... 17 2.7.1 Fasting plasma glucose test ................................................................................. 17 2.7.2 Oral glucose tolerance test (OGTT) .................................................................... 17 2.7.3 A1C test ............................................................................................................... 18 2.7.4 Autoantibody tests ............................................................................................... 18 2.8 The Roles of Insulin and Glucagon in Normal Blood Glucose Regulation ..... 18 2.9 The Mechanism of Alloxan Action on β-cells of Mice Pancreas ...................... 19 2.10 Management of Diabetes ................................................................................... 20 2.10.1 Insulin Therapy ................................................................................................. 20 2.10.2 Oral Hypoglycemic Drugs ................................................................................ 22 2.10.2.1 Sulphonylureas ............................................................................................... 22 2.10.2.2 Biguanides ...................................................................................................... 23 2.10.2.3 α-Glucosidase Inhibitor .................................................................................. 25 2.10.2.4 Thiazolidinedione ........................................................................................... 25 2.10.2.5 Incretin-Based Therapies ............................................................................... 26 2.11 Herbs and Diabetes Management ..................................................................... 27 2.11.1 Significance ....................................................................................................... 27 2.11.2 Garlic (Allium sativum) ..................................................................................... 30 2.11.3 Neem (Azadirachta indica) ............................................................................... 30 2.11.4 Onion (Allium cepa) .......................................................................................... 30 2.11.5 Salacia oblonga ................................................................................................. 31 2.11.6 Aloe vera ........................................................................................................... 31 2.11.7 Dandelion (Taraxacum officinale) .................................................................... 31 2.11.8 Turmeric (Curcuma longa) ............................................................................... 31 2.11.9 Bitter melon (Momordica charantia) ................................................................ 32 2.11.10 Cinnamon (Cinnamomum zeylanicum) ........................................................... 32 2.11 Plants of this Study............................................................................................... 32 2.11.1