ANTIDIABETIC and ANTIHYPERLIPIDEMIC EFFECTS of the LEAF EXTRACT and FRACTION of Alchornea Cordifolia (Schumach & Thonn.) Müll
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ANTIDIABETIC AND ANTIHYPERLIPIDEMIC EFFECTS OF THE LEAF EXTRACT AND FRACTION OF Alchornea cordifolia (Schumach & Thonn.) Müll. Arg ON STREPTOZOTOCIN-INDUCED DIABETIC WISTAR RATS BY MOHAMMED-RABIU, KARIMA DEPARTMENT OF BIOCHEMISTRY FACULTY OF SCIENCE AHMADU BELLO UNIVERSITY, ZARIA-NIGERIA MARCH, 2014 ANTIDIABETIC AND ANTIHYPERLIPIDEMIC EFFECTS OF THE LEAF EXTRACT AND FRACTION OF Alchornea cordifolia (Schumach & Thonn.) Müll. Arg ON STREPTOZOTOCIN-INDUCED DIABETIC WISTAR RATS By MOHAMMED-RABIU, KARIMA (MISS) B.Sc (BUK) 2007 M.Sc/SCIEN/05044/09-10 A Thesis Submitted to the Postgraduate School, Ahmadu Bello University, Zaria. In Partial fulfillment of the requirement for the Award of Master of Science Degree in Biochemistry Department of Biochemistry, Faculty of Science MARCH, 2014 DECLARATION The research works in this Thesis entitled ANTIDIABETIC AND ANTIHYPERLIPIDEMIC EFFECTS OF THE LEAF EXTRACT AND FRACTION OF Alchornea cordifolia (Schumach & Thonn.) Müll.Arg. ON STREPTOZOTOCIN INDUCED DIABETIC WISTAR RATS was carried out by me in the Department of Biochemistry. The information derived from the literature has been duly acknowledged in the text and a list of references provided. No part of this Thesis was previously presented for another degree or diploma at this or any other Institution. Mohammed-Rabiu Karima 09/03/2014 Name of Student Signature Date ii CERTIFICATION This Thesis entitled ANTIDIABETIC AND ANTIHYPERLIPIDEMIC EFFECTS OF THE LEAF EXTRACT AND FRACTION OF Alchornea cordifolia (Schumach & Thonn.) Müll.Arg. ON STREPTOZOTOCIN INDUCED DIABETIC WISTAR RATS, meets the regulations governing the award of the degree of Masters of Science of Ahmadu Bello University, Zaria, and is approved for its scientific contribution to knowledge and literary presentation. Dr. S. Ibrahim Chairman, Supervisory Committee Signature Date Prof. S, E. Atawodi Member, Supervisory Committee Signature Date Prof. I, A Umar Head of Department Signature Date Prof. A.A. Joshua Dean, Postgraduate School Signature Date iii ACKNOWLEDGEMENTS Immense praise and gratitude to Almighty Allah for all that he has blessed me with. Special gratitude goes to Chairman, Supervisory Committee, Dr. S. Ibrahim for his untiring support, unsurpassed encouragement, and motivation, a true source of inspiration. His contribution to the sound outcome of this work is immeasurable. My deepest gratitude goes to member, Supervisory Committee Prof. S.E. Atawodi for his enthusiastic guidance. His resourcefulness helped in the academic enrichment of this research work. My profound appreciation goes to Head of Department, Prof. I, A Umar for making available the facilities and enabling learning environment My sincere appreciation goes to Eze E. Daniel of Physiology Department, A.B.U, Zaria, especially for his assistance in animal handling. Many thanks go to Dr. I. A. Umar, Dr. B. Sallau, Dr. D. B. James, and all Laboratory Technologists of Biochemistry Department, A.B.U, Zaria. I also appreciate Hajiya L. Nasiru formally of Biochemistry Department, A.B.U, Zaria I wish to acknowledge the assistance of Dr. M. K. Atiku of Department of Biochemistry, Bayero University, Kano Utmost appreciation goes to my family members for their all-round support, love and care, without which I may not be able to keep afloat and swim to the riverbank; My parents, Alhaji Mohammed Rabiu and Hajiya Fatima Salis, you two beam with positive energy and hope for the future and that will always be a great source of inspiration for the family. Much gratitude goes to my siblings, Auwal, Aisha, Abubakar, Alhassan and Fatima for their comfort at all times. Warm appreciation goes to my friends, class colleagues; Maimuna Zubairu, Fatima Hassan, Abdulmalik Salman, Aliyu Sani, Oche, Ogechi, Mal. Ibrahim, Kingsley, Haroun, Amaya, Victoria, Samuel Atabo, Mfon, Chichi, Mayowa, Sarah, Chijioke, Chidi, Ewa and Jerry. iv ABSTRACT Aqueous concoction made from the crushed leaves of Alchornea cordifolia (Christmas bush) is used in Nigeria and other parts of Africa as a remedy for the treatment of diabetes mellitus and other ailments. The aim of the study was to evaluate the hypoglycemic and hypolipidemic effect of Alchornea cordifolia leaf extract and fraction in Streptozotocin-induced diabetic rats. Liver and heamatological biochemical parameters were also investigated. In the experiment, a total of forty five (45) rats were used. They were randomly divided into 9 groups of 5 rats each. Normal rats were assigned group 1, untreated diabetic rats were assigned group 2. Groups 3, 4 and 5 received varying doses (200, 400, 800 mg/kg bw/day) of n-butanol fraction of Alchornea cordifolia leaf ethanolic extract either extract/fraction or standard anti-diabetic drug daily for four (4) weeks, orally. Groups 6, 7 and 8 received varying doses (200, 400, 800 mg/kg bw/day) of ethanolic extract, while rats in group 9 were treated with the standard drug, glibenclamide (10mg/kg bw/day). After the 14th, 21st and 28th day treatment of diabetic rats with all doses of the plant extract and glibenclamide, there was a significant increase in the body weight of diabetic rats. The study showed that there was a significant reduction in the fasting blood sugar (FBG) levels in the entire streptozotocin-induced diabetic rats treated with ethanolic extract and its fraction, with a maximum reduction of 13.6% and 16.2% in the FBG level at 400 and 800mg/kg bw doses of n-butanol fraction respectively. There was significant decrease in the serum levels of total cholesterol, triglyceride, LDL-C and increased HDL-C in streptozotocin-induced diabetic treated groups, and percent reduction of 12.4% , 18.7% , 19.5% of TC, TAG, LDL-C respectively were observed in the groups treated with 800mg/kg n-butanol fraction when compared with the group of diabetic rats (85.3, 117.2, 91.9 %), and percent increase in the concentration of HDL-C, (10.8 and 12.9 %) was recorded in the group treated with 800mg/kg N- v butanol fraction and 800mg/kg ethanol extract respectively. Maximum reduction in the concentration of ALT, 2.7% was recorded in the group treated with 800mg/kg ethanol extract. A marked reduction in the concentration of AST, (2.51 and 2.42%) was observed in the groups treated with 400 and 800mg/kg N-butanol fraction respectively. A high decrease in the level of ALP, 5.4% was recorded in the group administered with 400mg/kg n-butanol fraction. The levels of TB and DCB were reduced significantly (0.4 and 0.6%) respectively for groups treated with 200mg/kg ethanol extract. There was a significant increase in packed cell volume, red cell count, haemoglobin concentration and total protein in the extract and glibenclamide treated diabetic. Total white blood cell count and lymphocyte revealed a significantly increased levels after treatment with the n-butanol fraction of Alchornea cordifolia leaf ethanol extract after 28th days. No death was recorded after three (3) weeks of sub-acute toxicity study. The histopathological studies of the pancreas of diabetic animals revealed the degeneration of pancreatic Islet cells, but with the restoration of pancreatic Islet cells in the pancreas of diabetic group treated with various doses of the plant extract. The implications of the results obtained in the present study provide the scientific rationale for the use of Alchornea cordifolia as antidiabetic agent in the management of diabetes and dyslipidemia usually associated with the disease. In addition, the plant had erythropoietic effect on the experimental animals. vi TABLE OF CONTENTS Contents Page Title…………………………………………………………………………………………...i Declaration……………………………………………………………………………………ii Certification…………………………………………………………………………………..iii Acknowledgement……………………………………………………………………………iv Abstract……………………………………………………………………………………….v Table of Contents……………………………………………………………………………..vii List of Tables………………………………………………………………………………….xiv List of Plates…………………………………………………………………………………..xvi Appendices……………………………………………………………………………………xvii Abbreviations…………………………………………………………………………………xviii CHAPTER ONE 1.0 INTRODUCTION………………………………………………………………………1 1.1 Statement of Research Problem…………………………………………………………4 1.2 Justification……………………………………………………………………………...4 1.3 Aim of the Study………………………………………………………………………..5 vii 1.6 Objectives of the Study…………………………………………………………………5 CHAPTER TWO 2.0 LITERATURE REVIEW………………………………………………………………..7 2.1 The Plant: Alchornea cordifolia (Schumach & Thonn) Müll.Arg……………………..7 2.1.1 Medicinal Properties of A. cordifolia…………………………………………………..10 2.1.2 Economic Importance of A. cordifolia………………………………………………………..12 2.1.3 Phytochemical constituents of A. cordifolia……………………………………………13 2.1.4 Research in Herbal Medicine…………………………………………………………...13 2.2 Blood Glucose Homeostasis and Metabolic Syndrome of Diabetes…………………….14 2.2.1 Blood Glucose Homeostasis……………………………………………………………..14 2.2.2 Metabolic Syndrome of Diabetes………………………………………………………..15 2.3 Complications of Diabetes Mellitus……………………………………………………...16 2.4 Insulin Management of Diabetes Mellitus………………………………………………17 2.4.1 Mechanism of Insulin Action…………………………………………………………...17 2.5 Blood Lipid Profile……………………………………………………………………...18 2.5.1 Plasma Cholesterol………………………………………………………………………18 2.5.2 Plasma Triacylglycerols………………………………………………………………….19 2.5.3 Low- Density Lipoprotein Cholesterol (LDL-C)………………………………………...20 viii 2.5.4 High - Density Lipoprotein Cholesterol (HDL-C)………………………………………..21 2.6 Hyperlipidemias and Antihyperlipidemic Drugs………………………………………….21 2.6.1 Hyperlipidemias…………………………………………………………………………...21 2.6.2 Antihyperlipidemic Drugs………………………………………………………………..22