European Journal of Scientific Research

ISSN 1450-216X Vol.33 No.4 (2009), pp.669-678

© EuroJournals Publishing, Inc. 2009
http://www.eurojournals.com/ejsr.htm

Hypoglycemic Effects of Ethanolic Extracts of Alligator Pear

Seed (Persea Americana Mill) in Rats

D. O. Edem
Department of Biochemistry,Faculty of Basic Medical Sciences
University of UYO,P.M.B. 1017, UYO,Akwa Ibom State,Nigeria
E-mail: doedem@yahoo.com
Tel: +234 0807 783 7175

Abstract

Effects of ethanolic extracts of alligator pear seed on normal and alloxan-induced

diabetic rats were investigated in 6 groups of rats (5 rats per group). Test groups were made
diabetic with intra-peritoneal injection of alloxan and treated with 450mg and 900mg/kg
body weight of alligator pear seed extract. Two non-diabetic groups were also administered
with 450mg and 900mg/kg body weight extract. The levels of blood glucose were
examined in all 6 experimental groups. In diabetic rats, blood glucose levels were
significantly reduced (p < 0.01) by 46.60 – 55.14 % on consumption of the extracts, with
greater effect exhibited by the 900mg/kg extract. In non-diabetic rats, blood glucose levels
were reduced by 14.62 – 17.33 % on consumption of the seed extract. Histological studies
showed a degenerative effect on the pancreatic islet cells of diabetic rats. The results
suggested restorative (protective) effect of the extract on pancreatic islet cells.
Administration of ethanolic extract of alligator pear seed may contribute significantly to the
reduction of blood glucose levels and can be useful in the management of diabetes.

Keywords: Alligator pear, Persia americana, seed extract, hypoglycemic effects.

Introduction
Plant medicine or phytomedicine (the sum total of practices, using herbal preparations produced by
physical or biological processes, to treat diseases relying on past experience/ observations handed
down from generation to generation) has been used in healthcare delivery in many parts of Africa and
the rest of the world. Effective health cannot be achieved in Africa, unless orthodox medicine is
complemented with traditional medicine (Elujoba et al, 2005). At least 80% of Africans depend on
plant medicine for their healthcare (Sofowora, 1993; Iwu et al, 1999; Calixto, 2000; Neuwinger, 2000;
Okigbo and Ajalie, 2005; Okigbo et al, 2005; Kilani, 2006; Okigbo and Mmeka, 2006; Ajose, 2007;
Okwu and Uchegbu, 2009). Today, medicinal plants are increasingly being used in most parts of the
world as: hypolipidemic (Ugochukwu et al, 2003; Ogbonnia et al, 2008; Yadav et al, 2008);
contraceptive, abortifacients, emmenagogues or oxytocic (Ritchie 2001); antihypertensive (Ojewole,
2005; Ofem et al 2007; Ojewole & Adewole, 2007; Nworgu et al 2008); treatment for skin diseases
(Ajose, 2007), wound healers (Biswas & Mukherjee, 2003); antimicrobial (Okigbo and Ajalie, 2005;
Okigbo et al 2005, Osadebe and Akabogu 2006; Okwu and Uchegbu, 2009) and hypoglycemic
(Eddouks et al, 2003; Maghrani et al 2003; Osadebe et al, 2004; Musabayane et al, 2006; Ogbonnia et
Hypoglycemic Effects of Ethanolic Extracts of Alligator Pear Seed
(Persea Americana Mill) in Rats 670

al, 2008; Patel et al, 2008; Yadav et al, 2008; Ajao et al, 2009; Farswan et al 2009; Lee et al 2009).
Hypoglycemic agents have been used in the management of diabetes mellitus.
Diabetes mellitus (DM) is a multifactorial disease which is characterized by hyperglycemia
(Scoppola et al 2001; Ugochukwu et al, 2003), lipoprotein abnormalities (Scoppola et al, 2001), raised
basal metabolic rate (Avesani et al 2001; Nawata et al, 2004; Owu et al, 2006), defect in reactive
oxygen species scavenging enzymes (Kesavulu et al, 2000) and altered intermediary metabolism of
major food substances (Avesani et al, 2001; Unwin et al, 2001; Nawata et al, 2004). Diabetes is a
major degenerative disease in the world today (Ogbonnia et al, 2008), affecting at least 15 million
people and having complications which include hypertension, atherosclerosis and microcirculatory
disorders. There has been increasing demand for the use of plant products with antidiabetic activity.
The high cost, low availability, uncertainty of use during pregnancy and undesirable side effects of
synthetic drugs have been some of the factors leading to a strong preference for hypoglycemic drugs of
plant origin, which are believed to be suitable for chronic treatments (Berger; 1985; Okigbo & Mmeka,
2006). Plants which have been shown to have hypoglycemic action, act on blood glucose through
different mechanisms. Some of them may inhibit endogenous glucose production (Eddouks et al, 2003)
or interfere with gastrointestinal glucose absorption (Musabayane et al 2006); some may have insulin -
like substances (Collier et al 1987; Gray and Flatt, 1999); some may inhibit insulinase activity and
some may increase secretion of insulin from the β cells of the pancreas i.e. pancreatotrophic action
(Khan et al,1990; Trivedi et al, 2004; Yadav et al, 2008), while others may increase beta cells in
pancreas by activating regeneration of these cells (Shanmugasundaram et al, 1990; Jelodar et al, 2007).
Very few traditional treatments for DM have been scientifically scrutinized. Thus it is the aim of this
study to investigate the hypoglycemic effect of the ethanolic extract of alligator pear seed (Persea
americana) used in traditional medicine for DM management and its possible role on pancreatic tissue.

Materials and Methods

Animals
Thirty (30) male Wistar albino rats weighing 152 - 238g were obtained from the Animal House of the
College of Health Sciences, University of Uyo, Uyo, Nigeria. The rats were kept in clean and only dry
plastic cages, with 12hrs light-dark cycle at 25 + 20C and 45-55% relative humidity. The animals were
fed with pelletized commercial rat feed (Pfizer Livestock Co. Ltd, Aba, Nigeria) and tap water ad
libitum. The rats were assigned into 6 groups of 5 rats each. All animal were treated in accordance with
the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NRC, 1985).

Sample Collection
Samples of ripe alligator pear (Persea americana) were purchased from markets in Uyo metropolis of
Akwa Ibom State in Nigeria. The plant material was authenticated by a taxonomist Dr (Mrs.) M.E.
Bassey of the Department of Botany and Ecological Studies, University of Uyo, Uyo, Nigeria. A
voucher specimen with number ‘Edem UUH 994’ has been deposited in the herbarium of the
University of Uyo. The samples were washed with clean tap water to remove dirt on the fruits. After
the fruits were kept for 2 hrs for the water to dry off, a sharp stainless steel knife was used to cut open
the fruits, in order to remove the seed. The seeds were chopped into very small pieces using a stainless
steel knife. They were then dried to constant weight in an oven at 550C. After drying, the seeds were
ground into fine powder (which passed through a 30 – mesh sieve).

Preparation of Ethanolic Extract of Alligator Pear Seed

One hundred grams (100g) of the ground seeds were soaked in 1 litre of 99.9% ethanol for 24hrs for
complete extraction. Thereafter, the mixture was filtered using cheesecloth and the extract obtained.
671 D. O. Edem

One hundred milliliters (100 ml) aliquots of the extract were poured into separated beakers of known
weight. The solutions were dried at 500C to constant weight using a rotary evaporator. The extract
concentration was determined by gravimetric method. One milliliter (1 ml) of the extract was
evaporated to obtain a residue of 100.0mg. The residue was dissolved in 1 ml of distilled water. Thus
the concentration of the extract was 100.0 mg/ml and 0.82ml of the solution administered to 182g rat
was equivalent to 450mg/kg body weight. Other doses per weight of rats were determined accordingly.

Animal Treatments
The 6 group of rats were as follows: Diabetic group 1 (DG -1), Diabetic group 2 (DG- 2), Diabetic
control (DC), Non –diabetic group 1 (NDG- 1), Non – diabetic group 2 (NDG-2) and Normal control
(NC). DG-1, DG-2 and DC groups were made hyperglycemic by intra – peritoneal injection of 150
mg/kg body weight (wt) of alloxan monohydrate (Sigma) dissolved in sterile distilled water. The NC
group was not treated with alloxan.
Diabetes was confirmed 3days after alloxan injection by determining the blood glucose
concentration using One Touch Basic Glucometer.
Then groups DG-1 and NDG-1 were administered with 450 mg/kg body weight of.the extract,
while groups DG-2 and NDC-2 were administered with 900 mg/kg body wt of the extract, daily for 14
days, by oral gavage. Groups DC and NC, which served as treatment controls, were gavaged with
distilled water.

Collection and Treatment of Samples

After 14 days, the animals were anaesthetized under chloroform vapour. Blood samples were obtained
by cardiac puncture. Aliquots of the blood were poured into screw-cap sample bottles containing
fluoride /oxalate anticoagulant for blood glucose determination. All analyses were carried out within
24 hrs of blood collection.

Blood Glucose Analysis

Blood glucose concentration was estimated by glucose oxidase method, using a reagent kit from
Randox Laboratory Ltd, UK.

Histopathological Study
On the last day of experiment, the tail parts of the pancreas were removed and kept in 10%
formaldehyde. Tissue processing was carried out by autotechnicon and the prepared 5µ thick sections
were mounted on slides and stained with hematoxylin and eosin (H & E). Stained sections were
morphologically evaluated.

Statistical Analysis
All data were expressed as means ± SD. Student’s t – test was used to compare the mean values of test
groups and control. Differences in mean values were considered significant at p < 0.01.

Results
The effects of aqueous extract of seed of Persea americana (alligator pear) on blood glucose
concentrations are shown in Table 1. The blood glucose concentrations in NC and DC groups were
3.84 mmol/L and 14.00 mmol/L respectively after the experimental period. In comparison with the DC
group, the other experimental groups had significantly lower mean blood sugar 3.10 – 7.69 mmol/L (p
< 0.05). No significant differences in blood sugar were observed between the diabetic group which
received 900mg/kg body wt extract (5.94mmol/L), and the normal control (NC) group (p > 0.01). The
non-diabetic groups (NDG) had lower glucose concentrations (3.10 – 3.33mmol/L) when compared
with the diabetic groups.
Hypoglycemic Effects of Ethanolic Extracts of Alligator Pear Seed
(Persea Americana Mill) in Rats 672

Table 1: Hypoglycemic Effects of Ethanolic Extract of Alligator Pear Seed*

Experimental Group
Plasma Glucose NC DC DG- 1 DG- 2 NDG- 1 NDG- 2
Concentrations 0 mg/kg body 0 mg/ 450 mg/ 900 mg/ 450mg/ 900 mg/
wt kgbody wt kgbody wt kgbody wt kgbody wt kgbody wt
Initial (mmol/L) 3.92 ± 0.31 a 15.11 ± 1.07b 14.40 ± 1.18b 13.24 ± 4.25b 3.90 ± 0.64a 3.75 ± 0.51a
a b c d
Final (mmol/L) 3.84 ± 0.36 14.00 ± 0.96 7.69 ± 0.90 5.94 ± 0.28 3.33 ± 0.49a 3.10 ± 0.62a
% reduction 2.04 7.36 46.60 55.14 14.62 17.33
Note: *Values are means ± standard deviation (n = 5). Values in same row with different superscripts in a horizontal row
represent means that are significantly different (p < 0.01).
Legend: NC = Normal Control DC = Diabetic Control
DG-1 = Diabetic Group 1 DG-2 = Diabetic Group 2
NDG-1 = Non diabetic Group 1 NDG-2 = Non diabetic Group 2

The results showed that treatment with 150mg/kg body wt alloxan after 3 days caused
significant increases (p < 0.01) in blood glucose levels of rats (mmol/L) in groups DC (15.11), DG-1
(14.40) and DG-2 (13.24), when compared with the NC and NDG groups (3.10 – 3.84). Treatment of
the hyperglycemic rats with 450mg/kg and 900mg/kg body wt of alligator pear seed extract resulted in
significant reductions (p < 0.01) of blood glucose (by 46.60 % and 55.14 % respectively), when
compared with the DC (a group without extract treatment), which had 7.36% reduction. The levels of
blood glucose in the non - diabetic groups (3.10 – 3.33mmol/L) were reduced after extract treatment
(by 14.62 – 17.33 %), when compared with the controls (2.04 – 7.36 % reduction).

Effects of Consumed Extracts on Histopathology of Pancreas: Histomorphologic Changes of

Pancreas
The cellular integrity and architecture were intact in the NC group (Figure 1). Pancreatic sections
stained with hematoxylin and eosin (H & E) showed that alloxan caused severe necrotic changes of
pancreatic islets, especially in the centre of islets. Nuclear changes, karyolysis, disappearance of
nucleus and in some places, residue of destroyed cells were visible. Relative reduction of size and
number of islets especially around the central vessel and severe reduction of beta cells were clearly
seen (Fig. 2).
673 D. O. Edem
Figure 1: NC (Normal control, 0mg/kg body wt extract) Pancreas of Normal Health Rat, H & E Staining (x
40)

Figure 2: DC (0mg/kg body wt extract) Pancreas of Diabetic Control Rat, H & E Staining (x 40)

Study of pancreas of treated diabetic groups (DG-1 and DG-2) showed increased size of islets
and hyperchromic nucleus in sections stained with H & E. These was also a relative increase of
granulated and normal beta cells in the diabetic group which consumed 900mg/kg body wt extract,
when compared with the diabetic group which consumed 450mg/kg body wt extract (Figs. 3 & 4
respectively). Pancreas of the non- diabetic group which consumed 450mg/kg body wt extract (Fig. 5),
showed close similarity to group NDG-2, which consumed 900mg/kg body wt extract (Fig. 6), NC
group (Fig. 1) and DG-2 group (Fig 4).
Hypoglycemic Effects of Ethanolic Extracts of Alligator Pear Seed
(Persea Americana Mill) in Rats 674

Figure 3: DG -1 Pancreas of Diabetic Rat Treated with 450mg/kg body wt extract,H & E Staining (x 40)

Figure 4: DG -2 Pancreas of Diabetic Rat Treated with 900mg/kg body wt extract,H & E Staining (x 40)

Figure 5: NDG – 1 Pancreas of Normal Rat Treated with 450mg/kg body wt extract, H & E Staining (x 40)

Figure 6: NDG – 2 Pancreas of Normal Rat Treated with 900mg/kg body wt extract, H & E Staining (x 40)
675 D. O. Edem

Discussion
The blood glucose concentration of the NC group (3.84mmol/L) is considered normoglycemic, while
that of the DC group (15.11mmol/L) is considered hyperglycemic for the experiment (Mayne, 1994;
Kaneko et al, 1997; Nimenibo-Uadia, 2003; Jelodar et al, 2007). There were significant reductions (p <
0.01) in blood glucose levels of the test groups (DG-1 and DG-2) and non- significant reductions (p >
0.01) for the non-diabetic groups that received extracts. Furthermore, the percentage reduction in
glucose levels is high for diabetic groups treated with extract. The results suggest both hypoglycemic
and antihyperglycemic effects of the alligator pear seed extracts. The findings may indicate the
presence of some hypoglycemic agents in the seed of alligator pear, which have been concentrated in
the extracts. The hypoglycemic effects of plants may be due to the presence of insulin-like substance in
plants (Collier et al, 1987; Gray and Flatt, 1999), stimulation of ß cells to produce more insulin (Khan
et al, 1990), increasing glucose metabolism (Broadhurst, 1997) or regenerative effect of plants on
pancreatic tissue (Shanmugasundaram et al, 1990; Jelodar et al, 2007).
In this study, the pancreatic ß cells were destroyed with the help of alloxan. Alloxan is one of
the usual substances used for the induction of diabetes mellitus apart from streptozotocin. Alloxan has
a destructive effect on the beta cells of the pancreas (Prince and Menon, 2000; Jelodar et al, 2007). The
pancreas is the primary organ involved in sensing the organism’s dietary and energetic states via
glucose concentration in the blood. In response to elevated blood glucose, insulin is secreted.
Histopathological study of diabetic untreated (DC) rats showed degeneration of pancreatic islet cells,
which was due to alloxan used in this study. This probably gave rise to insulin deficiency. Insulin
deficiency (or diabetes mellitus) causes excessive elevation of blood glucose and underutilization
leading to hyperglycemia (Standl et al, 2003). The histopathological study of diabetic treated group
(DG-1 and DG-2) indicated increased volume density of islets and increased percentage of beta cells,
in the diabetic rats that received the extracts, which may be a sign of regeneration. Signs of
regeneration of ß cells, potentiation of insulin secretion from surviving ß cells of the islets of
Langerhans and decrease of blood glucose have been reported following consumption of some plant
extracts (Shanmugasundaram et al, 1990; Abdel-Monein et al, 1997; Jelodar et al, 2007; Yadav et al,
2008). Alligator pear seed may have some chemical components that exert regenerative effects on ß
cells, stimulate these cells to produce more insulin (pancreatotrophic action) or may have some insulin-
like substances. Induction of regenerative stimulus in diabetic state triggers pancreatic regenerative
processes, thereby restoring functional activities of the pancreas (Adewole and Ojewole, 2007). A
higher dose of the extract has a greater restorative effect on the islet cells of diabetic rats than a lower
dose of extract. The hypoglycemic effect was more pronounced in alloxan-diabetic rats than in normal
rats.

Conclusion
The findings of this study indicate that consumption of the ethanolic extract of alligator pear seed
exerts significant hypoglycemic effect in diabetic rats. Histopathological studies of the pancreas of
diabetic treated rat show evidence of signs of regeneration of ß cells in groups receiving alligator pear
seed extracts. These findings support the traditional use of alligator pear seed for controlling
hyperglycemia in diabetics, in view of the restorative (protective) effects of the extract on pancreatic
islet cells. Further investigation with longer period of higher doses may show clearer features of these
findings.
Hypoglycemic Effects of Ethanolic Extracts of Alligator Pear Seed
(Persea Americana Mill) in Rats 676

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