ABSTRACT
Diabetes is becoming a pandemic disease
despite the recent surge in new drugs to manage the condition. The
limitations of currentlyavailable oral anti-diabetic agents either in terms of
efficacy/safety coupled with the emergence of diabetes into a global epidemic
have encouraged a concerted effort to search indigenous, inexpensive botanical
sources to manage diabetes more efficiently. Chrysophyllumalbidum (Linn) belongs to Sapotaceae family and is
commonly called African star apple. Its various usesas
anti-oxidant, antimicrobial and anti-hyperlipidemic agents have been described in the literature.This
study aimed at evaluating the nutritive and non-nutritive components and anti-diabetic properties of the edible
portions (seed-shell pericarp, pulp and skin) of C. albidum fruit in streptozotocin-induced diabetic male albino
rats.
The nutritive
and non- nutritive components in seed-shell pericarp, pulp and skin of C. albidum fruit were analyzed using standard methods.In
addition, the anti-diabetic capacity in different solvents of seed-shell pericarp, pulp and skin extracts of C.
albidum fruit using alpha-amylase and
alpha-glucosidase inhibitory assays were investigated. Furthermore, animal
studies were conducted, consisting of sixty rats and divided into four groups.
Diabetes was induced using 50mg/kg streptozotocin (i.p.), and a 70g/kg C. albidum fruit skin (CAFS) formulated diet was fed
to streptozotocin-induced diabetic rats for 28 days to
evaluate its anti-diabetic efficacy against
glibenclamide (2.5mg/kg b.w.) as standard. Fasting blood glucose levels and body
weights of rats were measured on weekly intervals starting with base line
untill the end of treatment. Other biochemical parameters such as serum
insulin, glycosylated haemoglobin,
hepatic glycogen, plasma and liver lipid profile contents were
evaluated at the end of
treatment.Histopathological
examinations of liver and pancreatic sections were also carried out.
Results
of nutritive composition revealed that CAFS contained the highest content of copper
(0.55mg/100g) and manganese (2.25mg/100g).
Also the non-nutritive contents of CAFSshowed the highest of saponin (0.41%), pectin
(0.44%), cellulose (2.76%), arabinose (4854.79mg/100g) and starch (29.15%),
compared with seed-shell pericarp and pulp. Hexane extract of CAFS exhibited the highest
inhibitory activities on alpha-amylase (96.70%) and alpha-glucosidase (86.93%)
at a concentration of 0.04mg/ml compared with other extracts studied. In vivo studies indicated that
CAFS-treated rats had increased body weight from 216.94g to 226.88g and
decreased fasting blood glucose from 289.11mg/dl to 122.66mg/dlbefore-
and after- treatment respectively. Results of studies at the end of treatment
revealed that CAFS-treatment significantly (p<0.05) increased levels of
serum insulin (7.40µU/ml) and hepatic glycogen (9.63mg/g wet tissue) while it
decreased glycosylated haemoglobin
(5.45%), compared with diabetic (untreated) control group. CAFS-treatment
reduced plasma and liver lipids except high density lipoprotein-cholesterol
compared with diabetic-untreated group. These results were comparable with the
standard drug-treated group. Histopathological analysis on liver and pancreas
of CAFS-treatedgroup showed regenerative effects.
As a result of anti-hyperglycemicand
anti-hyperlipidemic potentials
of CAFS,it can be concluded that CAFS may
have a considerable impact inpreventing the ill effects of diabetes and
lipid disorders in experimental diabetes. Thus, CAFS could be used as
therapeutic adjunct in the management of diabetes.
CHAPTER ONE
INTRODUCTION
1.1 Background to the Study
Dietary control is vital in the management of
diabetes. Reports from FAO (1998); WHO and FAO (2003) have shown that diets
with low saturated fat, cholesterol and glycemic index as well as high contents
of soluble fiber, vitamins and minerals are effective in the management of
diabetes. Low glycemic foods contain sugars that digest and absorbed slowly
into the blood and thus control blood sugar levels. The fiber-like substances
such as gums and pectin reduced blood postprandial glucose levels (Jenkins et al., 1978; Ou et al., 2001) while diabetic subjects fed xanthan gum have lower
fasting, postprandial serum glucose levels and total plasma cholesterol
(Osilesi et al., 1985). Jenkins et al. (1978) reported that daily intake of 5–10 g of soluble fiber from
different sources reduced serum cholesterol by 5–10%. Fruits serve as one of the best sources of
dietary fiber, minerals, Vitamins A, C and E and frequent intake of vegetables
and fruits have demonstrated a lowered risk of diabetes, heart disease,
hypertension, stroke and cancer (Southon, 2000; Wargovich, 2000). Fruits supply
carbohydrates in the form of soluble sugars, cellulose and starch (Nahar et al., 1998) and serve as source of
nutrient, appetizer and food supplement in a world faced with problem of food
scarcity.
Diabetes
mellitus (DM) is a worldwide endemic disease in terms of occurrence, cost of
medical care, and general complications (King et al.,
1998). The metabolism of protein, carbohydrate and
fat are affected in diabetic conditions, resulting in hyperglycemia. DM
complication is mainly associated with a high risk of coronary heart disease
(Giugliano et al., 1996),
atherosclerosis, stroke and peripheral vascular disease. The incidence of DM
world wide, is projected to increase from 4% in 1995 to 5.4% by the year 2025 (Mohamed et al.,
2006), with the utmost increases set to occur in the developing countries of
Africa, Asia and South America (WHO, 2008).
According to WHO (1994) and American Diabetes Association (2008),
diabetes mellitus can be classified into insulin-dependent diabetes mellitus,
IDDM (type 1 diabetes mellitus) and non- insulin- dependent diabetes mellitus,
NIDDM (type 2 diabetes mellitus). Insulin-dependent diabetes mellitus is
caused by cellular-mediated autoimmune damage to beta cells of the pancreas,
accounts for about 5% to 15% of diabetic cases and occurs mostly in children or
adolescents (Ranjan and
Ramanujam, 2002). Genetics and environmental factors are
implicated in the formation of IDDM.
Administration of exogenous
insulin is thus required to avert ketosis and preserve life (Lokesh and Amit,
2006). Non- insulin- dependent diabetes mellitus starts as
insulin resistance, accounts
for 85-95% of cases globally and occurs usually in
adults of 40 years and above
(WHO Regional Office for the South-East Asia, 2009). It is associated with
hyperglycemia and glycosuria. The risk factors increases with
age, lack of physical activity, obesity and impaired glucose tolerance.
Insulin resistance occurs when glucose is not properly utilized by the
cells leading to high blood glucose in circulation. To maintain blood glucose
level, the kidney excretes exess blood glucose through the urine and glucosuria
occurs with increased excretion of water and sodium when blood glucose level
exceeds the renal threshold (160 - 180 mg/L). The failure to use glucose by the
body cells, results to increase appetite (polyphagia) (Robinson et al., 1986). The summary of the
symptoms of diabetes is shown in Figure 1.
Insulin resistance is associated with
decreased glucose uptake and stimulation of muscle glycogen synthesis (Cline et al., 1999). In addition, alteration
of enzymatic activities like increased
phosphatase activity and/or seryl phosphorylation of the insulin receptor substrate by glycogen synthesis
kinase 3 (GSK- 3), have also been reported in some cases of type 2 diabetes
mellitus (Begum et al., 1991; Nadiv et al.,1994; Eldar-Finkelman and Krebs,
1997). Insulin resistance plays an important role in the etiology of many
disorders including obesity, NIDDM, glucose intolerance, hypertension and other
related disorders. It has been reported that autophosphorylation of insulin
receptor kinase and subsequent phosphorylation of its principal substrate,
IRS-1, are significantly lowered in insulin-responsive tissues of patient with
severe obesity or NIDDM (Nadiv et al., 1992).
Increased lipolysis and decreased lipogenesis occurred when there is a fall in
circulated insulin leading to fatty acids release from adipose tissues and
subsequently oxidized to ketone bodies in the liver. The rapid release of fatty
acids into the blood leads to increase level of blood cholesterol and the
formation of atherosclerosis (Khan and Ahmad, 1993). In diabetics, there is
increase in excreted nitrogen through deamination, which is accompanied by
cellular potassium excretion in urine when the muscle protein is broken down to
support gluconeogenesis in the liver.
Of the several approaches applied, to lower
and control the occurrence of diabetes, drug and diet therapies form the most
popular approaches. The most common approach are the drug therapy with four
distinct classes of oral hypoglycemic agents (biguanides, sulfonylureas,
thiazolidinediones and alpha-glucosidase inhibitors) currently being
recommended for use to treat NIDDM. In dietary therapy, dietary modifications with adequate
exercise are used to prevent excessive weight gain and obesity (Derek,
2001). Intake of diets with low total and saturated fat, limited protein
with replacement by complex carbohydrate and/or mono unsaturated fatty acids
are the recommended diets for type 2 diabetes patients. Controlled diets will improve the metabolic control in diabetic
subject and lower the risk of diabetes complications (Griver and Henry, 1994).
A large number of plants with hypoglycemic
activity have been reported in different animal models. Aloe vera, Acacia arabica,
Allium sativum L., Bombax ceiba L., Allium cepa, Brassicajuncea
(L.) Cassia auriculata L., Caesalpinia bonducella (L.) and Musa sapientum L. are some of the
scientifically validated antidiabetic plants (Modak et al., 2007).
Plant of Study
Chrysophyllum albidum (Linn), commonly called African star apple is
a forest tree species of Sapotaceae family (Figure 2). It is widely distributed
in Nigeria, Niger Republic and Uganda (Bada, 1997). C. albidum has various ethno-medicinal uses (Dalziel, 1937; Amusa et al., 2003) and across Nigeria, it is
locally called ‘‘agbalumo’’ in South Western Nigeria and “udara” in South Eastern
Nigeria.
The
fleshy pulp of C. albidum fruit is
taken as snack, the seeds serve as a source of oil for various uses and the
fruit is a good source of ascorbic acid (Adisa, 2000; Adepoju and Adeniji,
2012). C. albidum plants are rich in
natural antioxidants and can thus support health by preventing oxidative stress
related disease such as diabetics, cancer and coronary heart diseases (Burits
and Bucar, 2002). The antioxidants content in vegetables and fruits has been
associated with the diminished risk to chronic diseases by scavenging free radicals
and prevent cells damage (Halliwell, 1994).
The antimicrobial and phytochemical screening
of C. albidum seed cotyledon (Idowu et al., 2003; Okoli and Okere, 2010), leaves (Duyilemi and Lawal,
2009; Okoli and Okere, 2010; Kamba and Hassan 2011), root (Okoli and Okere,
2010), and stem bark (Adewoye et al., 2010;
Kamba and Hassan 2011) have been investigated. In addition, the
anti-hyperglycemic and hypolipidemic effects of C. albidum seed cotyledon ethanolic extract (Olorunnisola et al., 2008) and leaf ethanolic extract
(Adebayo et al., 2010) have been
reported. Adebayo et al., 2010, 2011a
and 2011b, have reported the antiplatelet, antioxidant and hepatoprotective
effects of C. albidum leaf while
Onyeka et al. (2012) and Omotosho et al. (2013) reported the antifertility
and antioxidant effects of C. albidum
root bark and fruit juice.
Nwadinigwe (1982); Edem et al. (1984); Adisa (2000); Ige and
Gbadamosi (2007); Ureigho (2010); Christopher and Dosunmu (2011); Oyebade et al. (2011); Adepoju and Adeniji (2012), have independently
analyzed the nutritional contents of C.
albidum pulp. Similarly, Ige and Gbadamosi (2007) analyzed the nutrient
compositions of C. albidum fruit-peel
(skin) and fruit juice. Ewansiha et al. (2011),
analyzed C. albidum seed shell pericarp for its nutritional compositions while Ajewole and Adeyeye
(1990), studied the physico-chemical
characteristics and fatty acid composition of the seed. However,
information on the nutrient contents of seed shell pericarp, fruit skin (peel)
and fruit pulp of C. albidum are scanty in available literature. In
addition, there is dearth of information on the efficacy of either of these
edible portions of C. albidum fruit as remedy for the management of DM. Therefore, this study was design
to investigate the nutrtitive and non-nutritive components and the antidiabetic
potentials of the edible portions of C.
albidum fruit.
1.2 Statement of the Problem
Diet has a vital role in the causes and
control of several obesity-associated chronic diseases, such as diabetes and
cardiovascular diseases. Current
research has increased on studying individual foods to understand their
specific role(s) and the mechanisms of action in the diminished risk to
diseases in humans. Diabetes has emerged into a global epidemic, inspite of the
recent search in new drugs to manage and prevent the condition; its prevalence
continues to soar with increased risks and diagnosis in both adult and children
(Ludwig and Ebbeling, 2001). In addition, many synthetic
hypoglycemic agents such as biguanides, sulfonylureas, α-glucosidase inhibitors
and insulin, commonly used for the treatment of diabetes are expensive and
associated with serious side effects (Gupta et al., 2010). Sulfonylureas (e.g.,
glibenclamide) cause severe hypoglycemia, biguanides (e.g., metformins) are
unsafe for patients with kidney problem, while α-glucosidase inhibitors cause
dose-related malabsorption, flatulence and abdominal bloating (Codario, 2005).
In addition, these hypoglycemic agents are not effective in the control of
hyperlipidemia condition, which usually accompanies the incidence of diabetes
(Derek, 2001). These associated problems with the synthetic oral anti-diabetic
agents in terms of inefficacy, non-safety coupled with the emergence of the
disease into a global epidemy have necessitate the search for more efficient
alternatives with little or no side effect (Ranjan and Ramanujam, 2002). The
plant kingdom, thus become a target for the search to develop indigenous,
inexpensive botanical sources by multinational drug and biologically active
lead compounds (Evans, 1996).
Since
ancient times, medicinal plants with various active principles and properties
have been used by laymen and physicians to cure a variety of human diseases
such as coronary heart disease, diabetes and cancer (Havsteen, 1984; Middleton et al., 2000). Medicinal plants offer
exciting opportunity to develop them into novel therapeutics due to their
multiple beneficial effects as manipulating carbohydrate metabolism by various
mechanisms, enhancing glucose uptake and utilization, restoring integrity and
prevention of pancreatic β-cells damage as well as the antioxidant properties.
In Nigeria, the populace is unaware of the high nutritional and nutraceutical
values of C. albidum fruit; it is
however considered as snack for the low-income earners. This has resulted into
an information gap of its utilization as a functional food for all and sundry.
1.3 Obective
of the Study
The
main objective is to evaluate the nutritive and non-nutritive components and
antidiabetic properties of the edible portions of C. albidum fruit (seed-shell pericarp, pulp and skin) in
streptozotocin-induced diabetic male albino rats.
The
specific objectives are to:
1
determine the nutritive and non-nutritivecomponents
of the edible portions of C. albidum fruit;
2
assess the potential capability of the
edible portions of C. albidum fruit in improving glucose tolerance,
insulin sensitivity and oxidative stress factors often associated with diabetes
mellitus;
3
compare the antidiabetic potency of the
edible portions of C. albidum fruit with that of referenced drug
(glibenclamide) and
4
determine the atherogenic and coronary
risk indices from the lipid profile of the edible portions of C. albidum
fruit.
1.4 Research
Questions
1
What are the nutritive and non-nutritive
constituents of the edible portions of C. albidum fruit?
2
Can the edible portions of C. albidum fruit
improve glucose tolerance, insulin sensitivity and oxidative stress factors
often associated with diabetes mellitus?
3
Can the edible portions of C. albidum fruit
be as potent as the referenced drug (glibenclamide) in the control of DM?
4
Will the atherogenic and coronary risk
indices of the edible portions of C. albidum fruit be low or high?
1.5 Hypotheses
The
null hypothesis and alternative hypothesis at p<0.05 are as stated below:
Ho1:The nutritive and non-nutritive
components of C. albidum edible
portions (seed-shell pericarp, pulp and skin) do not possess antihyperglycemic and
hypolipidemic properties.
Ho2:The nutritive and non-nutritive
components of C. albidum edible
portions (seed-shell
pericarp, pulp and skin) possess
antihyperglycemic and hypolipidemic properties.
1.6 Significance of the Study
The result of this
study would be of great significance to the scientific community because it
would provide evidence-based information on C. albidum fruit for
Nutritionists and Dietitians for dietary management of DM in various
communities. C. albidum fruit is readily available in the West Africa
sub-region, cheap and with adequate information on its contributions to dietary
management of DM. The results would serve as basis for useful information
gathering to Food scientists, Biochemists and Pharmacists to research further
on the medicinal potentials of C. albidum fruit. Results would also
provide valuable information for use in compiling the food composition table of
Nigerian food staples. Results would create public awareness of the use of C.
albidum fruit as remedy for the management of DM and improve its
consumption when in season. Equally, the results would draw positive attention to attract Scientists
to do further investigations on the efficacy of the fruit as remedy for the
management of diabetic vascular related complications and other nutritionally
related diseases.
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