INTRODUCTION
Hypertension is a medical word for high Blood Pressure (BP). Blood carries
nutrients and oxygen to our body and picks up waste like carbon dioxide
(Amran et al., 2004; Nammi et al., 2003; Dupuis et al.,
2005). The heart pumps blood through arteries and blood returns to the
heart through veins. Blood pressure is the push of blood against the walls
of the arteries. But if the blood is being pushed too hard against the
walls of the vessels, they might be damaged (Gillman et al., 1990).
High blood pressure is the long term and persistent increase in blood
pressure above the normal range, defined as a systolic blood pressure
at or above 140 mmHg or a diastolic blood pressure at or above 90 mm Hg.
The condition of high blood pressure is also known as hypertensive disease
(Antia and Okokon, 2005). Hypertension may be divided into two groups
(a) Primary or essential hypertension, where the definite cause for the
rise in blood pressure is not known. Although the cause of essential hypertension
is mainly three types-genetic factor, stress condition and intake of excess
Na+ salt; (b) Secondary hypertension that are usually considered
as drug induced and disease induced. Nifedipine belongs to the group of
drugs that are termed calcium channel blocking agents. These drugs affect
the movement of calcium into heart and blood vessel cells and cause a
relaxing effect of the muscles to allow an increased amount of blood flow
into the heart. Many of these calcium channel blockers are used to treat
angina pectoris and they are used to help reduce blood pressure (Gillman
et al., 1990).
Catharanthus is the dried whole plant of Catharanthus roseus (G.
Don (syn. Vinca rosea Linn.)), locally known as nayantara, belongs
to the family Apocynaceae. The plant is indigenous to Madagascar but now
found in tropical regions and cultivated as an ornamental plant in Southern
Florida, Africa, India, Thailand, Taiwan, Eastern Europe and Australia.
Catharanthus roseus is an erect ever blooming pubescent herb or
sub herb, 40-80 cm high, woody at the bases. Madagascar periwinkle`s most
potent constituent is the reserpine. Reserpine is recommended for the
treatment of hypertension, mild anxiety states and chronic psychoses (Singh
et al., 2001). It works by decreasing heart rate and relaxing the
blood vessels so that blood can flow more easily through the vessels.
In severe hypertension, reserpine may be used together with more potent
hypertensive drugs where reserpine enhances the reaction to bring about
the desired relief within a short time. Reserpine has a calming effect
in chronic psychoses involving anxiety, psychomotor hyperactivity or aggressive
behavior. Leaves of Catharanthus roseus possess hypotensive properties.
Catharanthus roseus also used as a cerebral vasodilator.
MATERIALS AND METHODS
Plant materials: Fresh leaves of Catharanthus roseus were
collected in November 2004 from the botanical garden of our University
and authenticated by the herbarium of Department of Botany, University
of Rajshahi, Rajshahi, Bangladesh.
Preparation of the plant sample: The fresh leaves were collected,
dried in the sun for 7 days and finally in an oven below 60 °C. The
dried plant material was ground into fine coarse powder and extracted
with ethanol in cold condition (Nikkon et al., 2003) and the extract
was given to the animals following the works of other investigators (Nikkon
et al., 2003; Nammi et al., 2003).
Preparation of dose of the plant extract: Catharanthus roseus
leaves extract was given as 200 mg kg-1 body weight of rats.
The average body weight of hypertensive rats was measured 155 ±
15 g. Thus the daily single dose of Catharanthus roseus leaves
extract was 30 mg/155 ± 15 g body weight of rats dissolved in 0.1
mL dimethylsulfoxide (DMSO) and then diluted with saline.
Dose preparation of antihypertensive drug: The daily dose of nifedipine
for human is 50 mg/70 kg body weight. According to the body weight the
dose of nifedipine required for rats were 0.1 mg/155 ± 15 g body
weight of rats dissolved in 0.1 mL dimethylsulfoxide (DMSO) and then diluted
with saline.
Animal model: Albino rats were purchased from International Center
for Diarrheal Disease Research, Bangladesh (ICDDR, B), Dhaka, Bangladesh.
Rats were allowed free access to distilled water. A cycle of light and
dark (12 h light and 12 h dark) and a temperature of 24 ± 2 °C
were maintained in the room. At first rats were anesthetized with diethyl
ether and 100 μL of adrenaline was injected into rats by intraperitoneal
(i.p.) injection using a 1 mL disposable syringe for consecutive 5 days
to induce hypertension. To confirm the induction of hypertension, the
serum cholesterol, serum triglyceride and blood glucose levels were measured
and compared with that of control rats that received only normal saline
(Gillman et al., 1990). The animals used in this study were cared
for in accordance with the guidelines for the animal experiment.
Experimental treatment of rats: The animals were randomly divided
into four groups. Group 1 was consisted of control rats which received
normal saline, Group 2 was consisted of Adrenaline Induced Hypertensive
Rats (AIHR), Group 3 was consisted Catharanthus roseus leaves extract
treated adrenaline induced hypertensive rats and Group 4 was consisted
of nifedipine treated adrenaline induced hypertensive rats to compare
pharmacological activities. Catharanthus roseus leaves extract
and commercial drug nifedipine were administered through intraperitoneal
(i.p) route for one week at their respective doses in every morning till
the completion of investigation. Treatment was done six times for obtaining
accurate result.
Description and measurement of different parameters: Before treatment
different biochemical parameters such as heart weight, Serum Triglyceride
Level (STL), Serum Cholesterol Level (SCL), Blood Glucose Level (BGL)
and body weight of Group 1 and Group 2 rats were measured. The rats were
sacrificed to collect blood sample and heart from each rat and investigated.
Collected blood samples were analyzed for the determination blood glucose
level by using BioLand G-423 glucose test meter (BioLand, Germany). Then
the data were compared with the standard value. Collected blood samples
about 1-2 mL was centrifuged at 4000 rpm for 10 min to separate the serum
to determine STL, SCL by measuring absorbance using UV spectrophotometer
(Shimidzu UV-1200, Tokyo, Japan), using wet reagent diagnostic kits (Boehringer
Mannheim, GmbH) according to manufacturer`s protocol.
Drugs and chemicals: Phosphate buffer, Sodium buffer, Potassium
dihydrogen phosphate, Ether (Diethyl either), 0.1N HCl, Acetone, Ethanol
were of analytical grade and purchased from the local agent (A.Q. Choudhury
and Co., Dhaka). Active nifedipine was a kind gift from the Square Pharmaceuticals
Ltd., Bangladesh.
Statistical analysis: In the whole animal study each group consisted
of six animals. Data were expressed as Mean ± SEM. Differences
in mean values between experimental groups were analyzed by unpaired t
test. A probability value of 0.05 (p<0.05) was considered to be significant.
RESULTS
The effects of leaves extract of Catharanthus roseus with nifedipine
on heart weight, STL, SCL, BGL and body weight were investigated in control
and Adrenaline Induced Hypertensive Rats (AIHR).
Effect of Catharanthus roseus leaves extract and nifedipine
on heart weight in adrenaline-induced hypertensive rats: The mean
heart weight of control, adrenaline induced hypertensive and leaves extract
of Catharanthus roseus and nifedipine treated animals are shown
in Fig. 1. Hypotensive and hypolipidemic effect were
observed in animals treated with Catharanthus roseus leaves extract
and nifedipine. To determine whether or not there was a statistically
significant difference achieved by the Catharanthus roseus leaves
extract and nifedipine during treatment one-way ANOVA followed by DMCT
was applied and compared with the AIHR. A significant reduction in heart
weight of Cath-treated and nife-treated animals were observed.
Effect of Catharanthus roseus leaves extract and nifedipine
on blood-glucose level in adrenaline-induced hypertensive rats: The
mean blood glucose level of control, adrenaline induced hypertensive and
leaves extract of Catharanthus roseus and nifedipine treated animals
are shown in Fig. 2. A significant decrease in blood
glucose level was observed in animals treated with Catharanthus roseus
leaves extract and nifedipine. To determine whether or not there was a
statistically significant difference achieved by the leaves extract of
Catharanthus roseus and nifedipine during treatment one-way ANOVA
followed by DMCT was applied and compared with the AIHR. A significant
reduction in blood glucose level of Cath-treated and Nife-treated animals
were observed.
|
| Fig. 1: |
Effect of Catharanthus roseus leaves extract
and nifedipine on heart weight in adrenaline-induced hypertensive
rats. The data are shown as Mean ± SEM (n = 6 in each case).
*** Indicates significant change in heart weight between AIHR and
Cath-treated, Nife-treated animals. Cath-Catharanthus roseus
leaves extract and Nife-nifedipine |
Effect of Catharanthus roseus leaves extract and nifedipine
on total serum triglyceride and serum cholesterol in adrenaline-induced
hypertensive rats: The mean serum total cholesterol and triglyceride
levels of control, adrenaline induced hypertensive and leaves extract
of Catharanthus roseus and nifedipine treated animals are shown
in Fig. 3. Hypotensive and hypolipidemic effects were
observed in animals treated with Catharanthus roseus leaves extract
and nifedipine. Significant decreases in serum triglyceride and serum
cholesterol level were observed in animals treated with leaves extract
of Catharanthus roseus and nifedipine. To determine whether or
not there was a statistically significant difference achieved by the leaves
extract of Catharanthus roseus and nifedipine during treatment one-way
ANOVA followed by DMCT was applied and compared with the AIHR. A significant
reduction in serum triglyceride level of the extracts of Cath-treated
and Nife-treated animals were observed.
|
| Fig. 2: |
Effect of Catharanthus roseus leaves extract
and nifedipine on blood-glucose level in adrenaline-induced hypertensive
rats. The data are shown as Mean ± SEM (n = 6 in each case).
*** Indicates significant change in heart weight between AIHR and
Cath-treated, Nife-treated animals. Cath-Catharanthus roseus leaves
extract and Nife-nifedipine |
|
| Fig. 3: |
Effect Catharanthus roseus leaves extract and
nifedipine on total serum triglyceride and serum cholesterol level
in adrenaline-induced hypertensive rats. The data are shown as Mean
± SEM (n = 6 in each case). *** Indicates significant change
in serum triglyceride level between AIHR and leaves extract of Cath-treated
animals, ** Indicates significant change in STL between AIHR and Nife-treated
animals, *** indicates significant change in serum cholesterol level
between AIHR and leaves extract of Cath-treated animals, Nife-treated
(p<0.0001) animals. Cath-Catharanthus roseus leaves extract
and Nife-nifedipine |
|
| Fig. 4: |
Effect of Catharanthus roseus and nifedipine
on body weight in adrenaline-induced hypertensive rats. The data are
shown as Mean ± SEM (n = 6 in each case). *** Indicates significant
change in body weight between AIHR and Cath-treated animals, *** Indicates
significant change in body weight between AIHR and Nife-treated animals.
Cath-Catharanthus roseus leaves extract and Nife-nifedipine |
Effect of Catharanthus roseus leaves extract and nifedipine
on body weight in adrenaline-induced hypertensive rats: The mean body
weight of Catharanthus roseus leaves extract and nifedipine treated
animals (after intraperitoneal administration of a single dose) are shown
in Fig. 4. Hypotensive and hypolipidemic effect were
observed in animals treated with Catharanthus roseus leaves extract
and nifedipine. A significant decrease in body weight was observed in
animals treated with leaves extract of Catharanthus roseus and
nifedipine. To determine whether or not there was a statistically significant
difference achieved by the extract and drug during treatment one-way ANOVA
followed by DMCT was applied and compared with the AIHR. A significant
reduction in body weight (Day 1 and 8) of leaves extract of Cath-treated
and Nife-treated animals were observed.
DISCUSSION
Hypertension is a common debilitating illness among peoples in both developed
and developing countries. Community surveys in industrialized countries
have shown a prevalence of 15-33% in people aged 30 years. The disease
continues to be a leading cause of morbidity and mortality from the coronary
artery disease and stroke. Fortunately, antihypertensive drug therapy
is available to reduce blood pressure to a normal level, which is necessary
to manage cardiovascular disease, coronary heart disease and other cardiovascular
related complications. In this respect, herbal drugs are helpful and render
encouraging results in comparison to synthetic drugs due to their fewer
side effects and easy availability (Miyata, 2007). In the present study
hypertension was induced in rats by intraperitoneal injection of adrenaline
in accordance to earlier observation (Boesen et al., 2005). Standard
value of body weight, heart weight, blood glucose level, serum triglyceride
level and serum cholesterol level were determined. Except serum triglyceride
level, the standard values of body weight, heart weight, blood glucose
level and serum cholesterol level were high in adrenaline induced hypertensive
rats when compared to control rats. Because of metabolic effects of adrenaline,
serum triglyceride level was low in hypertensive rats (Gillman et
al., 1990; Boesen et al., 2005). This study was performed to
analyze the differential effects of plant extract and nifedipine on body
weight, heart weight, blood glucose level, serum triglyceride level and
serum cholesterol level of hypertensive rats and compared with those of
control rats.
CONCLUSION
The present study revealed that Catharanthus roseus leaves extract
has got profound hypotensive and lipid lowering activity and this study
has similarity with previous investigation (Nikkon et al., 2003;
Setoguchi et al., 2002; Boesen et al., 2005). The mechanism
by which Catharanthus roseus leaves extract lowers blood pressure
is not yet fully established. However, the hypotensive action may be due
to the stimulation of the muscarinic receptors of the parasympathetic
nerve by the compounds or to their action as an antagonist of β-adrenergic
receptors but it may act as a Ca++ channel blocker (Amran et
al., 2004). From these overall results, we can conclude that the Catharanthus
roseus leaves extract possess hypotensive and lipid lowering effects.
The intake of Catharanthus roseus leaves extract as medicine or
as supplement to diet might have potential benefit in the treatment of
hypertension.
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