ABSTRACT
Type
2 diabetes (T2D) occurs when there is an advanced determent in insulin action
(insulin resistance, IR), which proceeds toβ-cell dysfunction. This present
study assessed the modulatory effects of Buchholziacoriacea(B.
coriacea) seeds extract in high fructose-fed, streptozotocin-induced T2D in
male Wistar rats.
Methanolic
extract (MEBC), hexane fraction (HFBC), ethyl acetate fraction (EFBC) and
n-butanol fraction of BC (BFBC) were prepared using 70% methanol and successive
solvent partitioning method respectively. Antioxidant activities of
1-1-diphenyl 2-picryl hydrazyl (DPPH), nitric oxide radical scavenging assay
(NOSA) and hydroxyl radical scavenging activities (HRSA) were assessed as well
as α-amylase inhibition in vitro.
High fructose (20%, p.o) (2 weeks) followed by streptozotocin (STZ) (40 mg/kg,
i.p.) (FRU + STZ) (day 14) administered to achieve T2D in vivo. Control normal and diabetic untreated (FRU + STZ) rats
were administered carboxymethyl
cellulose (CMC) (1 ml/kg, p.o). Diabetic treated rats received BFBC (20,
200, 400 mg/kg, p.o), metformin (7.14 mg/kg, p.o) and glibenclamide (0.07
mg/kg, p.o) respectively.
BFBC
had the highest percentage yield, DPPH and α-amylase inhibition activities,
although, EFBC had a better inhibitory activities on HRSA and NOSA
respectively. Also, untreated diabetic rats showed increase (p< 0.05 -
0.001) in blood glucose levels (BGLs), insulin (6 folds) and lipid peroxidation
(LPO) levels in pancreas when compared with normal group. BFBC (20, 200, 400
mg/kg) showed decrease (p< 0.05) in BGLs in a time dependent manner in the
BFBC treated animals.Similarly, BFBC produced a dose dependent decrease in
serum insulin levels by 51% (20 mg/kg), 54% (200 mg/kg) and 70% (400 mg/kg) respectively.These
effects were also comparable to metformin and glibenclamide. BFBC treatments
elevated (p> 0.05) high density lipoprotein, but decreased (p> 0.05)
triglycerides, total cholesterol and low density lipoprotein levels compared
with control group while it lowers plasma alkaline phosphatase activities and
urea (p< 0.05) compared with untreated group. BFBC (400 mg/kg) elevated
total protein levels in the pancreas and heart by 103% and 7% compared with the
untreated rats. Treatment of diabetic rats with BFBC elevated the body weights
by 21% (20 and 200 mg/kg) and 36% (400 mg/kg) respectively. BFBC when
administered did not significantly alter hematological, electrolytes and
antioxidant enzyme activities in all rats. Histological assessments showed that
sections of the pancreas, liver, kidney and heart from BFBC treated animals had
reduced tissue damage compared with the untreated groups. Fourteen (14)
bioactive compounds highest in oleic, stearic,
2-methyl-pyrrolidine-2-carboxylic, n-hexadecanoic, and 13-docosenoic acids were
present in BFBC given Gas-Chromatography/Mass-Spectrometry analysis.
Thediabetic
animal model was able to present the natural history of the disease in human
T2D. Also, BFBC doses used in this study demonstrate potentials against in vitro and in vivo oxidative stress, hyperinsulinaemia, dyslipidemia as well
as declension in β-cell function in T2D rat experiment. Further, application of
some derivatives of BFBC in the treatment of problems associated with T2Dmay be
useful.
CHAPTER ONE
INTRODUCTION
1.1 Background to the Study
Diabetes mellitus is referred to as a
metabolic disorder in which there is high glucose level in the blood as a
result of insulin deficiency, resistance or both (American Diabetes
Association, 2009). It has been deduced globally that the adult population with
diabetes will rise by 69% for the year 2030 (Shaw et al., 2010). Type 2 diabetes (T2D) occurs when there is an
advanced determent in insulin action (insulin resistance, IR), which proceeds
to β-cell dysfunction due to the failed ability of pancreatic β-cells to
compensate for IR (Srinivasan et al.,
2005). The number of people suffering from diabetes worldwide is estimated to
be 215 million and 80–90% of them from T2D (Procopiou and Philippe, 2005).
Sedentary lifestyle such as taking
high-calorie containing food, lack of exercise, ageing are all risk
factors for T2D and hence conduce to the recent rising prevalence of obesity
and T2D (Aude et al., 2004).
Streptozotocin (STZ) has been utilized broadly for induction of diabetes both
type 1 diabetes and T2D in experimental animals (Szkudelski, 2001).
Unfortunately, it lacks the ability to induce IR directly which is one of the
pathogenesis of T2D, rather, it induces diabetes from direct pancreatic β-cells
damage which resembles a typical T1D (Srinivasan et al., 2005).
1.2 Statement of the Problem
Reports gotten from various studies
showed that high fat or fructose diet induced IR in experimental animals but
failed to induce hyperglycemia (Srinivasan et al., 2005; Wilson and
Islam, 2012). In as much as giving animals a high fructose load alone can
induce IR, several weeks may be required to achieve this. Hence, the cost and
duration of the study will be high. More so, the animals can naturally develop
nutritional tolerance when exposed to longtime feeding with fructose without
developing signs and symptoms of IR and impaired glucose tolerance (Stark et al., 2000). Therefore, the search and
development of a suitable T2D rat model that will boycott the setbacks
experienced in using fructose or STZ as single agents to induce IR and T2D came
into place. Interestingly, the model has been achieved through a combined
effect of fructose and STZ. High fructose load induced IR while a low dose of
STZ caused the initial β cell dysfunction and subsequently hyperglycemia
(Wilson and Islam, 2012; Stalin et al., 2016). This model is a close
replica of the natural history of T2D and its metabolic features in humans.
More so, it is cheaper, readily available and useful for investigation of
various compounds. Plants have been used extensively for treatment of disease
due to the fact that they can produce multifarious basic biochemical and
organic substances such as carbohydrates, proteins, terpenes, steroids,
alkaloids and glycosides (Andrews, 1982).
Buchholzia Coriacea (B. Coriacea)
a perennial plant belonging to the family capparidaceae and genus Buchholzia is popularly known as
wonderful kola (Quattrochi-Umbetto, 2007). Earlier studies carried out on
different parts of this plant shows that it has great medicinal potentials (Oluseyi
and Francisca, 2009; Fred-Jaiyesimi et al.
2011; Adisa et al., 2011; Obembe et
al., 2012; Olaiya and Omolekan 2013; Ibrahim and Fagbohum, 2013; Enenchi
and Nwodo 2014; Eze et al.,
2015). However, there is currently no study carried out to assess the
efficacy of B. Coriacea in T2D.
Therefore, this present study assessed
the possible modulatory effects of BC on high fructose-fed, STZ-induced T2D in
male Wistar rats in order to ascertain its involvement and as well characterize
the active compounds that may be present.
Insulin resistance, hyperlipidaemia,
β-cell dysfunction and their associations are major risk factors for the
development of T2D and cardiovascular complications (Lender and Sysko, 2006).
To mitigate these serious complications and negative outcome of T2D, the
control not only of blood glucose but also of lipids is essential (Moller,
2001). More so, the available therapeutic options such as a combination of
synthetic hypolipidaemic and antidiabetic drugs have their own setbacks (Lender
and Sysko, 2006). Therefore, there is a
need for new agents which will be more effective, readily available and with
minimal side effects.
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1.3
Objective of the Study
The general
objective of this study was to evaluate the possible modulatory effects of the B.
coriacea seed extracts in high fructose-fed, streptozotocin-induced
T2D in male Wistar rats. The specific objectives are to:
1.
Carryout preliminary invitro analysis on the B.
coriacea seed extracts including phytochemical components, the
antioxidant properties and characterization of
the bioactive compounds using GC/MS;
2.
Carryout biochemical and oxidative
stress assays including blood glucose levels, serum insulin, hematology, body
electrolytes, liver function tests, renal function tests, lipid peroxidation,
reduced glutathione, superoxide dismutase, catalase and glutathione peroxidase.
3.
Carryout body and organ weights as well
as food and water intake assessments.
4.
Carryout the histopathology of the
pancreas, liver, heart and kidney.
1.4
Significance of the Study
This study will
increase our understanding of the pathophysiological role of fructose-fed,
streptozotocin-induced T2D in vivo as well as evaluate the possible
modulatory role of B. coriacea. In addition, it is hope that constituent
compounds present in B. coriacea would aid further scientific
investigations while contributing to the field of diabetology and or harnessing
drug discovery and development.
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Item Type: Postgraduate Material | Attribute: 104 pages | Chapters: 1-5
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