Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
Emeka. E.J. Iweala
Funmilayo D. Oludare
The aim of this study was to evaluate the individual and synergistic hypoglycaemic and biochemical effects of the ethanolic extracts of seeds of Parinari polyandra and Spondias mombin in alloxan-induced diabetic rats. The ethanolic extracts of the seeds of Parinari polyandra and Spondias mombin were obtained by soxhlet extraction and administered to non-diabetic and alloxan-induced diabetic albino rats. Parameters including blood glucose, alanine aminotransferase (ALT), aspartate transaminase (AST), lipid peroxidation, triglycerides, cholesterol, glutathione and total protein were checked using standard test kits and methods after administration of the extracts. Histological changes in the liver of the animal were also examined. The results obtained revealed that alanine aminotransferase (ALT), aspartate transaminase (AST), lipid peroxidation, triglycerides, cholesterol and glutathione did not change significantly (p≤0.05) in the animals treated with the plant extracts. Glucose and total protein levels were significantly reduced (p≤0.05) in the animals treated with the plant extracts. The histological changes showed the presence of fatty cells in the liver of alloxan-induced diabetic control and non diabetic rats administered both Parinari polyandra and Spondias mombin extracts. The implications of the results obtained especially reduction of glucose by Parinari polyandra and Spondias mombin is their potential use in management of diabetes and apparent effects on the liver when administered together.
to cite this article:
Emeka. E.J. Iweala and Funmilayo D. Oludare, 2011. Hypoglycemic Effect, Biochemical and Histological Changes of Spondias mombin Linn. and Parinari polyandra Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats. Journal of Pharmacology and Toxicology, 6: 101-112.
Received: June 04, 2010;
Accepted: July 15, 2010;
Published: September 02, 2010
Medicinal plants are widely used in management of diseases all over the world
(Aliyu et al., 2007; Adewunmi
and Ojewole, 2004). Historically, the use of medicinal plants is as old
as mankind and medicine. In Nigeria, several thousands of plant species have
been claimed to possess medicinal properties and employed in the treatment of
many ailments (Okigbo and Mmeka, 2006).
Diabetes is a disease associated with glucose metabolism resulting from defects
in insulin secretion and action (WHO, 1999). It is characterized
by hyperglycemia, glucosuria and several microvascular and macrovascular complications
(Brownlee, 2001; Virella-Lopes and
Virella, 2003). The complications of diabetes are linked to oxidative stress
induced by hyperglycemia which overcomes the bodys natural anti-oxidant
system (Kikkawa et al., 2003; Udoh
et al., 2007). In the later stages of diabetes, lipid metabolism
is affected and seen as hyperlipidemia and hypercholesterolemia which are risk
factors in artherosclerosis (Ross, 1999; Schwartz,
2006; Krishnakumar et al., 1999). There is
also the possibility of liver damage in diabetes due to increased gluconeogenesis
and ketogenesis (Felig et al.,1970). The incidence
of diabetes is on the rise and is estimated to be over 150 million worldwide
(Wild et al., 2004). There is yet no effective
cure for diabetes and the available drugs and insulin currently used in managing
the disease are associated with several undesirable side effects (Piedrola
et al., 2001; Yaryura-Tobias et al., 2001;
Gandhipuram et al., 2006). The undesirable side
effects and high cost of anti-diabetic drugs has led to search for plants with
hypoglycemic properties and their employment in the management of diabetes (Calixto,
2000; WHO, 2002). Several species of medicinal plants
used in traditional treatment and management of diabetes worldwide have been
evaluated (Brai et al., 2007; Gondwe
et al., 2008). The hypoglycemic properties of plants used in management
of diabetes are reported to be due to their content of flavonoids, glycosides,
alkaloids terpenoids, plant polysaccharides and other bioactive compounds. The
seeds of two medicinal plants namely Parinari polyandra and Spondias
mombin are commonly employed in ethno medicine management of diabetic conditions
in Nigeria. Parinari polyandra is a tropical plant belonging to the family,
Rosaceae and widely used to enhance fertility and relieve painful and inflammatory
conditions (Vongtau et al., 2004). Some species
of Parinari have been claimed to be effective in the treatment of veneral
diseases and erectile dysfunctions (Lans, 2007). Preliminary
nutritional and phytochemical screening of the plant extracts revealed the presence
of flavonoids, tannins, saponin and glycosides (Abolaji et
al., 2007; Vongtau et al., 2004).
Spondias mombin belongs to the tropical genus Anacardiaceae and its leaves
and fruits are mostly used in treating various diseases including diarrhea,
allegies, inflammatory conditions and microbial infections (Okolie
et al., 2008; Ajao et al., 1985).
It is also used in managing psychiatric disorders (Ayoka
et al., 2005). Spondias mombin leaves contain tannins, flavonoids,
saponins, alkaloids and phenols (Njoku and Akumefula, 2007).
The hypoglycemic activity of the methanolic stem extract of Parinari polyandra
has been reported (Vongtau et al., 2004). Also,
the antidiabetic activity of the methanol leaf extract of Spondias mombin
has been evaluated (Fred-Jaiyesimi et al., 2009).
This study is designed to study the individual and synergistic hypoglycaemic
and biochemical effects of the seeds of Parinari polyandra and Spondias
mombin in view of their unorthodox use in the traditional management of
diabetes in Nigeria.
MATERIALS AND METHODS
This study was carried out between November, 2009 to February, 2010 at the Department of Biological Sciences, Covenant University, Ota South West, Nigeria.
Collection, processing and extraction of seeds of Parinari polyandra and Spondias mombin: The seeds of Spondias mombin and Parinari polyandra were bought from a local market in Ogun State, Nigeria, identified, sorted, air-dried and ground to a coarse powdered form. Hundred grams of each of the plant seeds was extracted with 90% ethanol and the crude extracts concentrated to dryness.
Experimental design: Forty male albino rats aged six weeks old and with
an average weight of 45 g were used for the experiment. They were housed in
well ventilated cages and given normal rat chow and water ad libitum.
The rats were randomly distributed into eight groups consisting of five animals
each. Diabetes was induced in rats by administering 250 mg kg-1 of
alloxan intraperitonally and then checking the fasting blood sugar for hyperglycemia
after five days. Groups that were not administered alloxan for induction of
diabetes were administered normal saline. Rats were orally administered plant
extracts (100 mg kg-1) daily for ten days. Groups that were not given
plant extracts were administered normal saline which was the vehicle. Group
1 and 2 were the non-diabetic and diabetic controls administered with vehicle.
Group 3 and 4 were non-diabetic and administered Parinari polyandra
and Spondias mombin extracts (100 mg kg-1 b.wt.), respectively.
Group 5 were non-diabetic and co-administered Parinari polyandra and
Spondias mombin extracts (100 mg kg-1 b.wt.). Group 6 and
7 were diabetic and administered Parinari polyandra and Spondias mombin
extracts (100 mg kg-1 b.wt.), respectively. Group 8 were also diabetic
and co-administered Parinari polyandra and Spondias mombin extracts
(100 mg kg-1 b.wt.). The animals were weighed weekly throughout the
period of the experiment.
All the animal experiments and handling were carried according to standard protocols approved by animal research ethics committee of the department of biological sciences, Covenant University, Ota, Nigeria.
Collection of blood, organs and tissue samples: At the end of the experimental period, four animals from each group were anesthetized and blood samples collected in heparinised sample bottles. Serum samples were collected in non-heparinized sample bottles and allowed to clot before being centrifuged at 5000 rpm for 10 min. The livers were quickly removed and stored in 10% formyl saline.
Biochemical determinations: Glucose, aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) were determined using Cypress diagnostic
test kits. Total triglyceride and cholesterol were determined using test kits
(Linear chemicals). Total protein was determined by the Lowry method (Lowry
et al., 1951). Glutathione was determined using the method of Ellman
(1959). Lipid peroxidation was determined by the thiobarbituric acid reactive
substances (TBARS) method of Buege and Aust (1978).
Histological examination of liver tissue: Sections of liver tissue from
all the groups were processed for histological examination according to procedures
described by Disbrey and Rack (1970).
Statistical analysis: The results obtained were expressed as Mean±Standard deviation for triplicate determinations. Analysis of Variance (ANOVA) for a completely randomized design and Duncans multiple range tests were used to analyse data. Values were considered significant at p≤0.05.
The effect of administration of Parinari polyandra and Spondias mombin extracts on weight and the biochemical parameters in non diabetic rats are presented in Table 1. The results of the administration of Parinari polyandra and Spondias mombin extracts on weight and the biochemical parameters in alloxan-induced diabetic rats are provided in Table 2. Groups significant against the non-diabetic control (Positive control) are signified by (a) and the groups significant against alloxan-induced diabetic control (negative control) are signified by (b).
Generally there were no significant percentage weight changes in all the experimental groups but the group administered Parinari polyandra and Spondias mombin extracts showed the highest percentage increase in weight while the alloxan-induced diabetic rats administered Parinari polyandra and Spondias mombin extracts had the lowest.
There were significant reductions (p≤0.05) in glucose concentration in all the groups administered Parinari polyandra and Spondias mombin extracts except the alloxan-induced diabetic group co-administered both extracts. The changes in total protein in most of the groups were not significant (p≤0.05) except the alloxan-induced diabetic control and the non-diabetic group administered Parinari polyandra and Spondias mombin extracts, respectively. There were no significant changes in glutathione, cholesterol, triglyceride and lipid peroxidation levels. The activities of the liver enzymes including AST and ALT were not significantly changed (p≤0.05) in all the groups.
The histological features of liver tissues of the animals administered Parinari
polyandra and Spondias mombin extracts in all the groups are shown
in Fig. 1-8. The liver of the rats in all
the groups except those co-administered Parinari polyandra and Spondias
mombin extracts and the alloxan-induced diabetic control (Fig.
4, 5) showed normal histological characteristics with
preserved hepatic architecture and hepatocytes arranged in plates.
|| Photomicrograph of liver of non-diabetic control rats
|| Photomicrograph of liver of non-diabetic rats administered
Parinari polyandra extracts
|| Photomicrograph of liver of non-diabetic rats administered
Spondias mombin extracts
||Photomicrograph of liver of non-diabetic rats co-administered
Parinari polyandra and Spondias mombin extracts
|| Photomicrograph of liver of alloxan-induced diabetic control
||Photomicrograph of liver of alloxan-induced diabetic rats
administered Parinari polyandra extracts.
||Photomicrograph of liver of alloxan-induced diabetic rats
administered Spondias mombin extracts
||Photomicrograph of liver of alloxan-induced diabetic rats
co-administered Parinari polyandra and Spondias mombin extracts
The normal liver was devoid of vascular congestions, necrosis, fibrosis, haemorrhage
or fatty changes. The portal tracts contained the hepatic triads (artery, vein
and bile duct) and scanty inflammatory cellular infiltrates.
The results showed a general increase in body weight of animals with no significant percentage weight changes, indicating that the plants generally were not toxic to the animals.
The oral administration of ethanolic extracts of Spondias mombin and
Parinari polyandra caused a significant reduction in the blood glucose concentration
of the diabetic rats. Alloxan induces diabetes by destroying the beta-cells
of the Islets of Langerhans in the pancreas leading to reduction in synthesis
and release of insulin (Szkudelski, 2001). This model
has been used to study the anti diabetic effects of several plant products (Abdel-Barry
et al.,1997; Babu et al., 2002). The
hypoglycemic properties of numerous medicinal plants have been studied and reported
(Adeneye and Agbaje, 2008; Rajagopal
and Sasikala, 2008; Maroo et al., 2003; Vats
et al., 2002). Reduction in blood glucose by most bioactive compounds
from plants might act by one of several mechanisms including stimulation of
insulin secretion, increased repair or proliferation of β-cells and enhancing
the effects of insulin and adrenalin (Fayed et al.,
1998). The possible mechanism by which the ethanolic extracts of Spondias
mombin and Parinari polyandra reduced blood glucose concentration
of the diabetic rats may be either by increasing the pancreatic secretion of
insulin from the cells of islets of Langerhans or its release from bound
insulin (Pari and Amarnath, 2004). This mechanism of
action is suggested for other plants that have been studied (Chaude
et al., 2001; Krishna et al., 2004;
El-Demerdash et al., 2005; Alarcon-Aguilar
et al., 2005).
There was also a decrease in total protein in the alloxan-induced diabetic
control which could be attributed to the non-enzymatic glycation of proteins
seen in diabetes and which contributes to the long-term complications of the
disease (Vlassara et al., 1981). Oral administration
of ethanolic extracts of Spondias mombin and Parinari polyandra
significantly reduced total protein concentration in the non-diabetic animals.
Lipid peroxidation is one of the characteristic features of chronic diabetes
and insulin secretion is also closely associated with lipoxygenase-derived peroxides
(Metz, 1984). TBARS is the most commonly used indicator
of lipid peroxidation (Lyons, 1991). Glutathione (GSH)
is known to protect the cellular system against toxic effects of lipid peroxidation
(Nicotera and Orrenius, 1986). Decreased level of GSH
in the liver and kidney during diabetes represents its increased utilization
due to oxidative stress (Anuradha and Selvam, 1993).
In this study there was no significant difference in the lipid peroxidation
and GSH levels in the tissues of all the test groups. This indicates that the
extracts maintained the levels of GSH that are utilized during diabetes and
hence also stabilized lipid peroxidation. This finding is similar to studies
done on some antidiabetic plants (Ravikumar and Anuradha,
1999; Srinivasan et al., 2005; Adewole
and Caxton-Martins, 2006).
High cholesterol levels and hyperlipidemia are associated consequences of diabetes
(Mironova et al., 2000; Pepato
et al., 2003; Odetola et al., 2006).
In this study, cholesterol and triglyceride levels were not significantly changed
following treatments with ethanolic extracts of Spondias mombin and
Parinari polyandra. This result agrees with other cholesterol modulating
effects of several other plants (Rajagopal and Sasikala,
2008; Iweala and Okeke, 2005;
Dhandapani et al., 2002). The stabilization of triglyceride and cholesterol
levels in the rats by ethanolic extracts of Spondias mombin and Parinari
polyandra is related to their promotion of utilization of glucose and hence
depressed mobilization of fat (Momo et al., 2006).
This result implies that the plant extracts may be helpful in reducing the complications
of hyperlipidemia and hypercholesterolemia which coexist quite often in diabetics
(Sharma et al., 2003).
Aspartate transaminase (AST) and alanine transaminase (ALT) assay are important
in the diagnosis of liver damage caused by drug toxicity or harmful chemicals
(Nelson and Cox, 2005). In the present study, AST and
ALT levels in the test groups did not significantly change. Increase in liver
enzymes is an indication of liver damage. However, the histological changes
in the liver of the diabetic rats and the non diabetic group co-administered
both ethanolic extracts of Spondias mombin and Parinari polyandra
indicated hepatic damage. This means that administration of alloxan and co-administration
of the ethanolic extracts of Spondias mombin and Parinari polyandra
alters liver function in diabetes. This suggests a possible harmful synergistic
effect by both plants on the liver. This observation is similar to a study by
Raji et al. (2006) and corroborates the claim
that most medicinal preparations in traditional medicines contain a variety
of synergistically acting phytochemicals that act on a variety of targets by
various mechanisms (Tiwari and Madhusudana-Rao, 2002).
The implication of this is the questionable safety especially on the liver associated
with the traditional concurrent use of the seeds of Spondias mombin and
Parinari polyandra in management of diabetes. However, the non significant
changes in the liver enzymes in groups treated with the individual ethanolic
extracts of Spondias mombin and Parinari polyandra suggests no
apparent toxicity to the liver and hence improving its functions and enhancing
transport of glucose to ameliorate diabetes (Bhandarkar
and Khan, 2004). Several plants employed in the management of diabetes do
not express liver toxicity (Muthulingam, 2010; Hossain
and Bhattacharya, 2006).
Generally, the biological effects of ethanolic extracts of Spondias mombin
and Parinari polyandra are not unconnected with their active principles
including alkaloids, flavonoids, tannins, glycosides which have been reported
to have hypoglycaemic, hypolipidemic, hypocholesterolemic, antioxidant properties
amongst others (Oladele et al., 1995).
The results of the present study clearly indicate that the ethanolic extracts of seeds of Spondias mombin and Parinari polyandra have glucose lowering effects on alloxan-induced diabetic rats. It also reveals the possible hepatotoxic effect of co-administration of both S.mombin and P. polyandra extracts as commonly practiced in unorthodox traditional management of diabetes in Nigeria. Further studies are in progress to isolate the active principle and elucidate the exact mechanism of action of S. mombin and P. polyandra.
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