Anti-Obesity Activity of Vateria indica
linn. Stem Bark in Rats
Shanal Smitha Alva, Himanshu Joshi*, Gururaja M. P,
Prasanna Shama K , Ullas P D’souza
Department of Pharmacology, Nitte Gulabi Shetty
Memorial Institute of Pharmaceutical Sciences,
Paneer, Deralakatte, Mangalore, 575018. India
*Corresponding Author E-mail:
visithjoshi@gmail.com, hjoshi@nitte.edu.in
ABSTRACT:
Vateria indica Linn. is a tree belonging to Family Dipterocarpaceae
and has been traditionally used for lipid disorders. The present study was
performed to study the antiobesity effect of Vateria indica Linn. stem
bark against high fat diet induced obesity models in albino wistar rats. Rats
were fed with high fat diet (HFD) for 12 weeks. Aqueous extract of Vateria
indica stem bark (AVIB) was administered orally in three doses i.e. 100,
200 and 400mg/kg body weight to the treatment groups. The following parameters
were recorded – body weight, organ weights and various biochemical parameters
like total cholesterol, triglycerides, HDL, LDL and VLDL. There was significant
(p<0.05) reduction in body weights, liver weight, kidney weight, spleen
weight, cholesterol, triglycerides, LDL and VLDL after treatment with AVIB on
HFD fed rats. Hence AVIB showed a significant dose dependent antiobesity effect
against HFD model. Preliminary phytochemical qualitative analysis of the
aqueous extract of Vateria indica stem bark showed the presence of
carbohydrates, flavanoids, resins, tannins and saponins. Hence the probable
mechanism by which the Vateria indica stem bark showed anti-obesity
activity could be due to its bile acid sequestering property or due to the
presence of flavanoids. The bark of Vateria indica may be a potential
candidate for further research leading to the development of herbal therapeutic
agent for obesity.
KEYWORDS: High fat diet, Obesity, Vateria indica.
INTRODUCTION:
Obesity is considered to be a chronic disease with
excess fat accumulation in the body. Obesity can be caused due to the imbalance
in the energy intake and expenditure. It is said to increase the risk factor
for other diseases like diabetes, stroke etc1. Most common reasons
of obesity is consumption of high fat diets, fast foods and sedentary
lifestyles2. Fat rich diets do not only induce obesity in humans but
also in animals like mice and rats. The literature review showed that the rats
which consumed the diet which contains more proportion of fat gained more
weight than the rats which consumed less proportion. Not only the fat amount
but also the type of the fat to be given plays an important role.
Obesity can be induced in experimental animals either
by adding fat to their diet or by giving them marketed fat diets3.
Body mass index is calculated by dividing the body weight by the square root of
body height. Individual having a body mass index more than30 kg/m2
is said to be obese4. In rats the BMI is measured by dividing weight
of the rat by square of nose to anus length and a BMI of more than 0.68 g/m2 is
considered to be obese5.
Herbal drugs are used by most of the people across the
world for treatment of various diseases since they have lesser side effects and
due to their compatibility with the human body6. The drugs used for
the treatment have various side effects like constipation, dry mouth etc and
many of the drugs have been withdrawn from the market due to serious adverse
effects. The most common mechanisms by which the drugs act might be by
inhibiting the pancreatic lipase activity or by inhibiting the lipid
absorption. Herbal products have been used from the ancient times for the
treatment of hyperlipidaemia and obesity but a large number of natural agents
for the treatment of obesity is still being unexplored. Hence the exploration
of naturally available medicinal plants is important2,4.
Vateria indica is a tree of Dipterocarpaceae family
found usually in the south west coast in Karnataka, Kerala and Tamilnadu. A
resin called as sarja rasa is obtained by incising the trunk of the tree which
has good traditional medicinal importance. A preparation called as Kungiliya
parpam is made from this resin along with tender coconut water which is used
traditionally for burning micturation, leucorrhea, urethritis, duodenal ulcer,
diarhhoea etc7. Bark contains polyphenols- dl-epicatechin, levorotatory
isomers of fisetinidol, fzelechin, bergenin. Resin present in it is a complex
mixture of triterpene hydrocarbons, ketones, acids, alcohols, sesequiterpenes,
azulenes. Fruit shell contains tannins. Hope phenol and bergenin is present in
leaves and roots. The Ayurvedic pharmacopoeiea has mentioned the use of
resinous exudates of Vateria indica bark in the treatment of lipid disorders8.
Hence in this study an attempt has been made to evaluate its anti-obesity
activity using high fat diet induced obesity model.
MATERIALS AND METHODS:
Plant material:
Vateria indica linn. stem bark was collected from local areas around
Udupi, Karnataka.
Preparation of extract:
The aqueous extract of the Vateria indica stem bark
was prepared by boiling 20g of the powdered bark in 300ml of water. The
resulting decoction was filtered and the filtrate was evapourated to dryness.
The extract was stored in descicator until further use. The %yield was found to
be 16%.
High fat diet induced obesity:
Male albino wistar rats 4-5 weeks old, weighing 80-90
g were obtained from central animal house NUCARE, Deralakatte, Mangalore. The
animals were grouped and housed in cages. They were maintained under standard
laboratory conditions i.e temperature 25+-5
with dark and light cycle (12h/12h). They
were allowed free access to the standard dry pellet diet and water ad libitum.
The experiment was carried out according to the CPCSEA guidelines and was
approved by the Institutional Animal Ethics Committee (IAEC)9. In
this experiment the rats were fed with the high fat diet and water ad libitum
form12 weeks. The composition of HFD (g/kg) was according to the following
formula shown in the table.
Table: Composition of HFD10,11
|
Ingredients
|
Composition (g/kg)
|
|
Powdered NPD
|
610
|
|
Cholesterol
|
10
|
|
Fructose
|
90
|
|
Lard
|
90
|
|
Coconut oil
|
200
|
Experimental design:12
In this study 30 animals were divided into five groups
of 6 animals in each.
Group I: rats were maintained on standard chow diet
for twelve weeks
Group II: rats were fed with high fat diet for twelve
weeks
Group III: rats were given aqueous extract of Vateria
indica stem bark (100mg/kg/day p.o) once for six weeks along with HFD starting
at the end of sixth week and continued up to the end of twelve weeks
Group IV: rats were given aqueous extract of Vateria
indica stem bark (200mg/kg/day p.o) once for six weeks along with HFD starting
at the end of sixth week and continued up to the end of twelve weeks
Group V: rats were given aqueous extract of Vateria
indica stem bark (400mg/kg/day p.o) once for six weeks along with HFD starting
at the end of sixth week and continued up to the end of twelve weeks.
Body weights were measured twice every week till 12
weeks. At the end of twelve weeks (85th day) rats were anaesthetised
using isoflurane anaesthesia and the blood was withdrawn by retroorbital method
and serum was obtained by centrifugation and was used for the lipid profile
analysis using commercial kit. After collection of the blood rats were
sacrificed and the liver, spleen, kidney was removed and washed with saline and
immediately weighed.
Statistical analysis:
The data was expressed as Mean ± SEM and analysed by
using one way analysis of variance (ANOVA), followed by Post hoc Scheffe’s test
using SPSS computer software version 16.0. A p value less than 0.05 was
considered as statistically significant.
RESULTS:
Body weights:
The animals which were fed with HFD for 12 weeks
showed significant increase in the body weights when compared to the normal
animals which were fed with NPD. During first six weeks before onset of
treatment the body weights of treatment groups was increased significantly when
compared to the normal group. After treatment for six weeks a dose dependant
significant reduction in the body weights was seen in the groups treated with
AVIB (100, 200, 400mg/kg) respectively when compared to the HFD control group.
Figure 1: Effect of AVIB on body weights
Serum biochemical parameters:
Cholesterol:
There was significant elevation in the cholesterol
levels of HFD fed group when compared to the normal group animals. A dose
dependant significant reduction in the cholesterol levels was seen in the group
treated with AVIB (100, 200, 400 mg/kg) respectively when compared to the HFD
control group. However the test extract at the dose of 400mg/kg reduced the
cholesterol levels significantly (p<0.05) and was comparable to the HFD
control group.
Triglycerides:
There was significant elevation in the triglycerides
level of HFD fed group when compared to that of the normal group animals. A
dose dependant significant reduction in the triglycerides level was seen in the
group treated with AVIB (100, 200, 400 mg/kg) respectively when compared to the
HFD control group. However the test extract at the dose of 200 and 400 mg/kg
reduced the triglycerides level significantly (p<0.05) and was comparable to
the HFD control group.
HDL:
There was decrease in the HDL levels of HFD fed group
when compared to that of the normal group. A dose
dependant increase in the serum HDL levels was observed
in the animals treated with AVIB (100, 200, 400mg/kg) respectively when
compared to the HFD control group.
LDL:
There was significant elevation in the LDL levels of
HFD fed group when compared to that of the normal group animals. A dose
dependant significant reduction in the LDL levels was seen in the group treated
with AVIB (100, 200, 400 mg/kg) respectively when compared to the HFD control
group. However the test extract at the dose of 400 mg/kg reduced the LDL levels
significantly (p<0.05) and was comparable to the HFD control group.
VLDL:
There was significant elevation in the VLDL level of
HFD fed group when compared to that of the normal group animals. A dose
dependant significant reduction
in the VLDL level was seen in
the group treated with AVIB (100, 200, 400 mg/kg) respectively when compared to
the HFD control group. However the test extract at the dose of 200 and 400
mg/kg reduced the VLDL level significantly (p<0.05) and was comparable to
the HFD control group.
Organ weights:
Effect on liver weight as percentage of body weight:
To access the effect of AVIB on liver weight of
animals, liver weight was taken on last day of the experiment and expressed as
liver weight as percentage of body weight. There was significant elevation in
the liver weight of HFD fed group when compared to the normal group animals. A
dose dependant reduction in the liver weight was seen in the group treated with
AVIB (100, 200, 400 mg/kg) respectively when compared to the HFD control group.
However the test extract at the dose of 200 and 400mg/kg reduced the liver
weight significantly (p<0.05) and was comparable to the HFD control group.
Figure 2: The serum lipid profile (mg/ dL) levels
Figure 3: Effect of AVIB on organ weights as percentage
of body weight
Effect on kidney weight as percentage of body weight:
To access the effect of AVIB on kidney weight of
animals, kidney weight was taken on last day of the experiment and expressed as
kidney weight as percentage of body weight. There was significant elevation in
the kidney weight of HFD fed group when compared to the normal group animals. A
dose dependant reduction in the kidney weight was seen in the group treated
with AVIB (100, 200, 400 mg/kg) respectively when compared to the HFD control
group. However the test extract at the dose of 400mg/kg reduced the liver
weight significantly (p<0.05) and was comparable to the HFD control group.
Effect on spleen weight as percentage of body weight:
To access the effect of AVIB on spleen weight of
animals, spleen weight was taken on last day of the experiment and expressed as
spleen weight as percentage of body weight. There was significant elevation in
the spleen weight of HFD fed group when compared to the normal group animals. A
dose dependant reduction in the spleen weight was seen in the group treated
with AVIB (100, 200, 400 mg/kg) respectively when compared to the HFD control
group. However the test extract at the dose of 400mg/kg reduced the spleen
weight significantly (p<0.05) and was comparable to the HFD control group.
DISCUSSION:
The present study was done to evaluate the antiobesity
activity of AVIB using HFD induced obesity model. Preliminary phytochemical
qualitative analysis of the plant extract showed the presence of carbohydrates,
flavanoids, resins, tannins and saponins. There are number of animal models
which resemble obesity like in humans. HFD induced obesity and MSG induced
obesity are among these models. In HFD induced obesity model the rats are fed
with high amount of fat which leads to increase in lipid profile, body and
organs weights and also causes accumulation of fat in the body13.
Obesity in the present decade is mainly because of
sedentary life style and consumption of easily available fast food which mainly
contain monosodium glutamate and fats14.
When the food reaches intestine, certain resins called
as bile acid binding resins bind to the bile acids and hence decrease their
enterohepatic circulation and convert the cholesterol into bile acids15.
Resins are neither absorbed nor digested from the intestine but they bind
to the bile acids present in the intestine and interrupt their enterohepatic
circulation and cause its fecal excreation. Acetyl CoA cholesterol acyl
transferases (ACAT) is required for the cholesterol absorption in the intestine
and for the production of VLDL in the liver. Flavanoids decrease the activity
of HMG CoA reductase and ACAT hence cause the decrease in plasma cholesterol
levels16,17.
Several studies have confirmed the increase in weight,
organ weights and lipid profile when animals are treated with HFD. In this
study the AVIB reduced the serum lipids significantly indicating its
antihyperlipidemic activity. It also reduced the body weights and organ weights
which could be compared to the control group. The stem bark of Vateria indica
is known to contain resins and flavanoids. Hence the probable
mechanism by which the Vateria indica stem bark showed anti-obesity
activity could be due to its bile acid sequestering property or due to
flavanoids. Hence it can be suggested to use Vateria indica stem bark
extract for obesity treatment but to know the exact mechanism of action further
investigation is necessary.
CONCLUSION:
Vateria indica is a well known tree and usually found in the south
west coast region of India. It is used widely in the Siddha system for the
treatment of cough, piles, rheumatism, bacterial infections, leucorrhera,
ulcers, urethritis etc. Traditionally it is also used for weight reduction in
south canara area. From literature survey it was learnt that the resinous
exudates from Vateria indica can be used to treat lipid disorders but no
specific studies were done on its antiobesity activity. Hence an effort was
made to evaluate its antiobesity activity against HFD induced obesity. The
preliminary phytochemical study done on aqueous extract revealed the presence
of reducing sugar, flavanoids, resins, tannins and saponins. The acute oral
toxicity studies showed that the aqueous extract of Vateria indica was
found to be safe till 2000mg/kg body weight. Extract was given to animals using
three different doses i.e. 100, 200 and 400 mg/kg body weight. The anti-obesity
effect was assessed in terms of serum total cholesterol, triglycerides, HDL,
LDL, VLDL. The body weight and organ weights were also assessed in both the
models. The extract treated groups showed significant reduction in the serum
lipids. The body weights and organ weights were also reduced dose dependently.
Based on these results it can be concluded that the aqueous extract of Vateria
indica stem bark posseses antiobesity activity but to understand the exact
mechanism of action further investigation is necessary.
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