Hypoglycaemic effects of some medicinal plant extracts in streptozotocin-induced diabetic rats

291 Pages·2014·6.15 MB·English

Hypoglycaemic effects of some medicinal
plant extracts in streptozotocin-induced
diabetic rats
By
Mavuto Masopera Gondwe
A dissertation submitted to the Faculty of Health Sciences for the
degree of Doctor of Philosophy, PhD-Physiology, University of
KwaZulu-Natal
Supervisor: Professor C. T. Musabayane
Co-supervisors: Professor J.A.O Ojewole
Professor F.O. Shode
Date submitted: 2007
DECLARATION
I, Mavuto Gondwe, hereby declare that the dissertation entitled
'Hypoglycaemic effects of some medicinal plant extracts in
streptozotocin-induced diabetic rats'
is the result of my own investigation and research and that it has not been submitted in
part or in full for any other degree or to any other university. Where use was made of
the work of others, it is duly acknowledged in the text.
J 080256
~ ~v
Student: Mavuto M. Gondwe
a1
Supervisor: Professor CT Musabayane
To my late grand mother and grandfather; my mother andfather;
My wife Lilly and
Francis, Enoch and Chitatata, for their love and support
II
ACKNOWLEDGEMENTS
I wish to acknowledge the invaluable contribution of the following, without whose
input, this work would not have materialised:
I am deeply indebted to Professor C.T. Musabayane, for constantly
providing guidance and supervision, for his patience and dedication, and
for constructive criticisms and financial support for all the requirements of
this research from the start to finish;
Professor l.A.O. Ojewole, for constant supervIsIOn, encouragement,
reviews and constructive criticisms;
Professor F.O. Shode, for the supervIsIon, advice and encouragement
during phytochemical studies in his laboratory;
Professor H. Baignath, for identifying and supplying the plant material
used in the study. I was humbled and honoured to work with you. Thank
you for being such an inspiration to me;
Professor A. Chuturgoon, for the guidance and support during my cell
culture studies in his laboratory;
Professor Anita Naicker for help with histology micrographs;
111
Dr A. Nadar, Ms K. Moodley and other members of staff of Physiology
department, UKZN, for support rendered in ways too numerous to mention
I wish to specially acknowledge the technical assistance rendered to me by
members of staff of Biomedical Resource Unit, especially Dr S. Singh,
Linda Bester, David, Dennis and Rita.
It would be utterly ungrateful of me not to acknowledge the contributions
of David Rexon Kamadyaapa, my comrade since Chancellor College days,
at the University of Malawi. Thank you for being a good friend and
companion during good and bad times, alike. Thank you.
Last but not least I would like to thank in a very special way, the
Norwegian government through their NORAD project, and College of
Medicine, University of Malawi, for providing me with funding to pursue
my doctoral studies.
IV
ABBREVIATIONS
a Alpha
AGE Advanced glycation end-product
AIDS Acquired Immune deficiency syndrome
AMPK adenosine monophosphate protein kinase
APE African potato (Hypoxis hemerocallidea) ethanolic extract
ATP Adenosine triphosphate
Beta
~
BB Biobreeding
CCM Complete culture medium
Copper ion
CYP Cytochrome P
DCCT Diabetes Control and Complications Trial
dG deoxyguanosine
DMSO Dimethyl sulphoxide
DNA Deoxyribonucleic acid
EDRF Endothelium - derived relaxing factor
EMEM Eagle's Minimum Essential Medium
PTE: Ficus thonningi ethanolic extract
GLUT-I Glucose transporter-l
GLUT-2 Glucose transporter-2
GLUT-3 Glucose transporter-3
GLUT-4 Glucose transporter-4
GLUT-5 Glucose transporter-5
h Hour
v
H S04: Sulphuric acid
2
HBSS Hank's balanced salt solution
HCI Hydrochloric acid
HDL High density lipoproteins
h-HSD Hydroxysteroid dehydrogenase
HIV Human immunodeficiency virus
HLA Histocompatibility leucocyte antigen
IL Interleukin
IR Insulin resistance
IRS Insulin receptor substrate
Potassium
Kg: kilogram
LDL Low density lipoprotein
MAP Mean arterial pressure
MHC: Major histocompatibility complex
Ilg rrucrogram
III microlitre
mg milligram
mmHg Millimetres of mercury
mmol millimole
MMP Matrix metalloproteinase
MTT (3,4,5-dimethylthiazol-2-yl)-5-5diphenyltetrazolium bromide
MODY: Maturity Onset Diabetes of the Young
NaCl: Sodium chloride
NADPH Nicotinamide adenine dinucleotide phosphate
VI
NF-KB Necrosis factor- kappa B
ng nanogram
NIDDM Non-insulin dependent diabetes mellitus
NO Nitric oxide
NOD Non-obese diabetic
NPY Neuropeptide Y
O - Superoxide
2
OGTT Oral glucose tolerance test
ONOO- Peroxynitrite
PAE Persea americana ethanolic extract
PAl-I: Plasminogen activator inhibitor-I
PGh Prostaglandin
2
PKC Protein kinase C
PPAR-"( Perixosome proliferator gamma receptors
RAGE Advanced glycation end-product receptor
SBE Sc/erocarya birrea ethanolic extract
sc Subcutaneous
SEM Standard error of mean
SHR Spontaneously hypertensive rats
STZ Streptozotocin
p:
TGF- Transforming growth factor-p
TNF-a. Tumour necrosis factor- a.
TZD Thiazolidinedione
UKPDS United Kingdom Prospective Diabetes Study (UKPDS)
UKZN University ofKwaZulu-Natal
VB
USA. United States of America
VEGF Vascular endothelial growth factor
WHO World Health Organisation
WKY Wi star-Kyoto
Vlll
CONTENTS
Page no.
Declaration
ii
Dedication
Acknowledgements III
Abbreviations v
Contents IX
List of Tables xviii
List of Figures xx
List of Appendices XXIV
Abstract XXVI
CHAPTER 1 1
1.0. Introduction and Literature review 1
1.1. Diabetes mellitus 1
1.1.1. Diabetes mellitus in Africa 2
1.2. Glucose homeostasis 3
1.2.1. Glucose transport into cells 4
1.2.2. Insulin secretion 5
1.2.3. The metabolic effects of insulin 5
1.2.4. Insulin regulatory and counteregulatory hormones 6
1.2.5. Insulin resistance 8
ix