COMPARATIVE EFFECTIVENESS SOURSOP LEAF EXTRACT (Annona muricate Linn) AND SIMVASTATIN

OF CHANGES IN LIPID FRACTION LEVELS IN WHITE MALE RATS (Rattus norvegicus)

Mufia Muin, Prema Hapsari Hidayati, Indah Lestari, Gina Isni D Iskandar, Nurul Faiqah, Agung Sukriadi
Indonesian Muslim University School of Medicine, Makassar, Indonesia

ABSTRACT

Background : Dyslipidemia associated with a high mortality rate from cardiovascular disease. Soursop leaves is one of the
traditional medicines that can lower blood cholesterol levels. Research on the effectiveness of soursop leaf in lowering
cholesterol levels is still lacking.
Purpose : Knowing the comparative effectiveness of soursop leaf extract and simvastatin to changes in lipid fractions levels
in white male rats.
Method :This study design is one group pre-test post-test on 15 male rats were divided into 3 groups. The first group was
given soursop leaf extract, the second group were given simvastatin and the third group was given a placebo
Results: At baseline, the mean total cholesterol level is 182.4 mg / dL, triglycerides 107.4 mg / dl, LDL 94 mg / dL, and
HDL 24 mg / dl. After being given a soursop leaf extract obtained average total cholesterol of 136.2 mg / dL (p = 0,05),
Triglycerides 90.40 mg / dL (p = 0.028), LDL 81.00 mg / dL (p = 0.040), HDL of 28.8 mg / dL (p = 0.015). When compared
with the simvastatin group found no significant difference in total cholesterol reduction (p = 0.003) and triglycerides (p =
0.016). As for the levels of LDL (p = 0.186) and HDL (p = 0.085) no significant difference
conclusion:Soursop leaf extract has the effect to improve blood cholesterol levels even though its effectiveness is lower than
simvastatin

Keywords : Cholesterol, LDL, triglycerides, HDL, leaves of the soursop, Annona muricate
abbreviations:LDL: Low Density Lipoprotein; HDL: High Density Lipoprotein

However, the price of medicines are expensive, cause not

everyone can reach it 4 and these drugs also cause a
INTRODUCTION variety of side effects, namely hepatotoxicity,
rhabdomyolysis, abdominal pain, constipation, asthenia
Coronary heart disease (CHD) is an important health headaches, nausea , hypersensitivity reactions, myopathy
problem because of the high morbidity and mortality. and rabdomiolisis.6,9
According to the World Health Organization, 84.5% of
all causes of death are heart disease.18 While the data Annona muricata Linn. it known as soursop in
shows in riskesdas 2013 the prevalence of coronary heart Indonesia, are found from Central America, South
disease in Indonesia amounted to 1.5% while the number America, including North America, Northeast and
increased with age increasing. 1,2 Southeast regions of Brazil. Not many people know that
this soursop plant is commonly used as a drug.
Dyslipidemia is a condition wherein abnormality of Traditionally, the leaves used to treat headaches,
cholesterol levels in the blood.2 Cholesterol is present in insomnia, cystitis, liver disease, diabetes, hypertension
conjunction with triglycerides, phospholipids and and as an anti-inflammatory, antispasmodic and
apoproteins to form lipoproteins. Lipoproteins in the disentry.12,
blood, namely chylomicrons, Very Low Density
Lipoprotein (VLDL), Low Density Lipoprotein (LDL) Based on the qualitative identification of metabolic
and high density lipoprotein (HDL). Normal cholesterol compounds and phytochemical screening results that
levels in the blood ranges from 160-200 mg / dL, a soursop leaf extract contains tannins, glikosid, saponins
higher level of cholesterol in the blood, the greater the and flavonoids. Cholesterol reduction is due metabolic
risk of aterosklerosis.3,19 compounds contained in extracts of soursop leaf.13,16

The diagnosis of dyslipidemia enforced if obtained Flavonoids can lower blood cholesterol levels by
increased LDL, increased total cholesterol, increased increasing the excretion of bile acids and reduce the
triglycerides, decreased HDL. In Indonesia based on data thickness (viscosity) of blood, thereby reducing the
from the national basic medical research (RISKESDAS) deposition of fat on artery.10,11 Flavonoids also have the
in 2013 showed there were 35.9% of the Indonesian effect of inhibiting the enzyme HMG Co A reductase so
population aged ≥ 15 years with abnormal cholesterol that it can work to lower cholesterol17 while saponins
levels. RISKEDAS data also showed 15.9% of the inhibit cholesterol absorption in the intestine.
population aged ≥ 15 years has a very high proportion of Consequences inhibition of cholesterol absorption of
LDL (≥190 mg / dl), 22.9% had HDL less than 40 mg / cholesterol is removed from the body with feces which is
dl, and 11.9% with very high triglyceride levels (≥ 500 the main pathway to removing cholesterol.13
mg / dl) 2.3
Therefore, researchers interested in conducting
The management of dyslipidemia is one of the health research on the comparative effectiveness of soursop leaf
care measures that prevent heart disease. Decreased extract and simvastatin to changes in lipid fractions
levels of cholesterol can be done with drugs, one levels in male white rats (Rattus norvegicus) induced
example is an analog statin.8,17,18 Statins 3-hydroxy-3- high fat.
methylglutaryl-coenzyme A (HMGKoA). Simvastatin,
pravastatin and fluvastatin is a drug that similar.7
 METHODS (LSD) for comparison of each group as shown in Table
4.
This research is an analytic study using
experimental designs to approach one group pre-test Paired T test showed that the treatment group
post-test. soursop leaf extract is obtained prior to intervention
mean total cholesterol by 182.40 mg / dL and after the
Materials used in this study included white male rats
intervention amounted to 136.20 mg / dL, with a value p
(Rattus norvegicus), feed the standard diet, fatty beef and
(0,05) <0.05 which means there is a significant
corned beef as food hiperkolestrolemik, distilled water,
proportion. Similarly, in the group taking the drug
leaves of the soursop (Annona muricata Linn), 70%
simvastatin was obtained prior to intervention mean total
ethanol and placebo.
cholesterol of 339.4 mg / dL and after the intervention
Determination of the samples using the provisions amounted to 174.80 mg / dL, with a p-value (0.001)
of the WHO that is the number of samples of at least 5 <0.05 which means there is a significant proportion.
mice per group were taken randomly.14 This study were There are significant differences between the decrease in
divided into three groups: the first group as negative total cholesterol levels soursop leaf extract group
controls were given a placebo, while group two and compared with simvastatin with a p-value (0.003)> 0.05.
group three as positive controls were given the leaf
Paired T test showed that the treatment group
extract soursop and simvastatin with sample consisted of
soursop leaf extract is obtained prior to intervention
5 mice per group in order to get the total sample of 15
mean triglyceride level of 107.4 mg / dL and after the
rats. Initially, all of the group was given the standard
intervention amounted to 90.40 mg / dL, with a value p
feed for 7 days. Then all groups were fed
(0.028) <0.05 which means there is a significant
hiperkolestrolemik for 7 days. After that, each group was
proportion. Similarly, in the group taking the drug
given treatment that the first group was given no
simvastatin was obtained prior to intervention mean
treatment, two groups were given the leaf extract of
triglyceride levels of 146.0 mg / dL and after the
soursop and three groups were given simvastatin. Blood
intervention amounted to 86.80 mg / dL, with a p-value
sampling performed on days 15 and 22.
(0.009) <0.05 which means there is a significant
Measurement of lipid fraction of mice was done by proportion. There are significant differences between the
rats mempuasakan day prior to blood sampling. His groups decrease triglyceride levels soursop leaf extract
blood was then taken to make the injury section of Vena compared with simvastatin with a p-value (0.016)> 0.05.
caudalis using a lancet and blood coming out of injury
Paired T test showed that the treatment group
and strip incorporated into the lipid profile cholesterol
soursop leaf extract obtained before the intervention of
lipid test pro and wait about 3 minutes and showed levels
the mean levels of LDL 94.00 mg / dL and after the
of total cholesterol, LDL, HDL and triglycerides.
intervention amounted to 81.00 mg / dL, with a value p
The data obtained were statistically analyzed using (0.040) <0.05 which means there is a significant
the program Statistical Products and Service Solutions proportion. Similarly, in the group taking the drug
(SPSS) for Windows Release 23.0. Do homogeneity simvastatin was obtained prior to intervention mean LDL
Shapiro-Wilk test to see the normality of the data levels of 118.0 mg / dL and after the intervention
distribution. Where the value of p> 0.05, normal amounted to 95.60 mg / dL, with a p-value (0.007) <0.05
distribution, so that the data analysis technique used is which means there is a significant proportion. There were
the one-way ANOVA test to see generally mean different no significant differences between the groups in LDL
lipid fractions levels before and after treatment. If the levels decrease soursop leaf extract compared with
result of a significant ANOVA test then followed by a simvastatin with p (0186)> 0.05
post hoc test (Tukey) was used to determine the mean
Paired T test showed that the treatment group
couples most different between groups. The procedure
soursop leaf extract is obtained prior to intervention
used in the Post Hoc Tests is the Least Significant
mean HDL levels by 24.80 mg / dL and after the
Difference (LSD). Data in group I and II were also
intervention amounted to 28.80 mg / dL, with a value p
analyzed statistically using the Paired Samples T Tests.
(0.015) <0.05 which means there is a significant
This test is used to determine whether Leaf Extract
proportion. Similarly, in the group taking the drug
Soursop (Annona muricata) is able to influence the level
simvastatin was obtained prior to intervention mean HDL
of blood lipid fractions white male rats.
levels by 20.60 mg / dL and after the intervention
amounted to 27.20 mg / dL, with a p-value (0.001) <0.05
RESULTS which means there is a significant proportion. There were
Lipid fractions levels before and after treatment and no significant differences between groups increased
simvastatin soursop leaf extract for 3 weeks are levels of HDL soursop leaf extract compared with
presented in Table 1. Proceed with Normality Test to see simvastatin with p (0089)> 0.05.
whether the data were normally distributed with a value
of p> 0.05 which means the normal distribution of data
as is presented in Table 2. Once known that the normal
distribution of data then continued with Paired t test to
see if there is a comparison before and after treatment (p
<0.05), as shown in Table 3. Test Forum POCT Hoc
Table 1 Levels of Lipid Fraction Before And After Giving Soursop Leaf Extract, simvastatin and placebo
Triglyceride Levels The mean levels of The mean levels of
Average Cholesterol
Mean LDL HDL
(mg / dL)
(mg / dL) (mg / dL) (mg / dL)

Before After Before After Before After Before After

group I
(Soursop Leaf 182.4 136.2 107.4 90.4 94 81 24.8 28.8
Extract)
group II
339.4 147.8 148 86.8 118 95.6 20.8 27.2
(Simvastatin)
group III
166.2 140.2 86 82.4 92.8 92 25.8 25.8
(Placebo)

Table 2. Shapiro-wilk Normality Test

Sig.

Cholesterol Triglycerides LDL HDL

Before 0.164 0.508 0.928 0.985

Group
I
After 0.062 0.118 0.595 0.687

Before 0.198 0.613 0.560 0.940

Group
II
After 0.602 0.205 0.729 0.924

Table 3. Paired T Test

The p-value

Cholesterol triglycerides LDL HDL

group I 0:05 0018 0000 0002

group II 0001 0028 0040 0002

Table 4. Post
Hoc Test The p-value
(LSD) The group (vs)
Cholesterol triglycerides LDL HDL

group I group III 0705 0028 0094 0015

group II group III 0001 0009 0007 0001

group I group II 0003 0016 0186 0089

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