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

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

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

 DISCUSSION
Soursop leaf extract (Annona muricata L) can 1.
improve blood lipid fraction level, because there are a
variety of metabolic compounds in soursop leaf extract.
Based on the qualitative identification of compounds in
the leaves of the soursop found several metabolic
compounds are tannins, glikosid, saponins and
flavonoids that can lower cholesterol levels, and as an
antioxidant.12, 13 2.
In this study, we used a mouse model to test the
effect of soursop leaf extract supplementation on total
cholesterol and lipid profile in rats efevtivitas 3.
hiperkolesterolemik and compare results between
soursop leaf extract and simvastatin. There is a
significant difference between the experimental group 4.
and the control group as in the total cholesterol and
triglycerides. There is a considerable decline, although
not as great as on the levels of HDL and LDL. 5.
Based on analysis of statistical tests observed a
considerable reduction in total cholesterol and 6.
triglycerides in soursop leaf extract to rats
hiperkolesterolemik. This is consistent with research
Lelly et al (2016) in Bandung that get results that soursop 7.
leaves have the same effect as simvastatin in reducing
cholesterol.19
From the results of our study, the levels of HDL and 8.
LDL are significant results in mice given the extract of
leaves of the soursop and simvastatin, there is a 9.
considerable reduction in LDL cholesterol and a slight
increase in HDL levels. However, there are significant
comparisons between the use of soursop leaf and
simvastatin. This is consistent with research Wulandari et
al (2015) in Semarang who get results are not significant
when comparing the soursop leaf extract and simvastatin, 10.
maybe a longer time will be able to have an even greater
impact.21
But the differing results obtained in the study 11.
Tugianty et al (2016) in Purwokerto obtain significant
results in increased levels of HDL whereas no significant 12.
results in decreased levels of total cholesterol, LDL and
triglycerides.22
13.
This study has shown that an extract of soursop leaf
outline can inhibit the absorption of cholesterol that can
lower total cholesterol and lipid profiles levels
memperbaki. From the observed results indicate that the 14.
soursop leaf extract with simvastatin comparison impact
on reducing total cholesterol and triglyceride levels
significantly, and decreased levels of LDL and increase
HDL levels were less significant.
15.
CONCLUSION
As a conclusion in this study we get a significant
result in changes in total cholesterol and triglyceride 16.
levels after administration of soursop leaf extract and
simvastatin, but we obtained significant results on the
levels of HDL and LDL in comparison between soursop
leaf extracts and simvastatin.
REFERENCES
Barquera S, Pedrosa-Tobias A, Medina C,
Hernandez- Barera L, Bibbins-Domingo K,
Lozano R et al. Global Overview of the
Epidemiology of Atherosclerotic
Cardiovascular Disease. Archives of Medical
Research 2015. Available at
http://dx.doi.org/10.1016/j.arcmed.2015.06.006
Riset Kesehatan Dasar. Badan Penelitian dan
Pengembangan Kesehatan Kementrian
Kesehatan Republik Indonesia. Jakarta,
2013:91-93.
Karam I, Yang YJ, Li JY. Hyperlipidemia
Background and Progress. SM Atheroscler J.
2017; 1 (1):1003
Arsana PM, Rosandi R. Panduan Pengelolaan
Dislipidemia Di Indonesia.PB PERKENI,
2015:5-7
Musunuru K. Atherogenic Dyslipidemia :
Cardiovascular Risk And Dietary
Intervention.Lipids, 2010;45 (10):907-914.
Sacher, Ronald A, Richard A. Tinjauan Klinis
Hasil Pemeriksaan Laboratorium.Edisi
II.Jakarta : EGC, 2004:25-28
Freeman M, Junge C. Kolesterol Rendah
Jantung Sehat. Jakarta, Buana Ilmu Populer,
2005:23-27
Mardiana L, Ratnasari J. Ramuan & Khasiat
Sirsak.Jakarta, Penebar Swadaya, 2011:59-61
Putri TT. Uji Efektivitas Ekstrak Buah Naga
Merah (Hylocereus polyrhizus) dan
Simvastatin terhadap Penurunan Kadar
Kolesterol Total Mencit Jantan (Mus musculus
L.) Hiperkoleterolemia. Universitas Lampung,
2017
Romdani R, Erwinanto. Pedoman Tatalaksana
Dislipidemia Perhimpunan Dokter Spesialis
Kardiovaskular Indonesia Edisi I.Jakarta,
2013:21-26
Katzung BG. Farmakologi Dasar dan Klinik.
Jakarta, Salemba Medika, 2005;2: 422-446.
Asprey GF dan Thornton P.Medical plants of
Jamaica Part 1-11, 2, West Indian Journal,
2000:1-86.
Zarrabal CO, Waliszewski SM, Barradas
dermitz DM, olascohipolito ZC, Rican S dan
Trujillo PRL.The Consumption Of
Hibiscus,2005
Wurdianing I, Nugraheni SA, Rahfiludin Z.
Efek Ekstrak Daun Sirsak ( Annona muricata
L.) Terhadap Profil Lipid Tikus Putih Jantan
(Rattus novergicus). Jurnal Gizi Indonesia
(ISSN : 1858-4942), 2014;3 (1):7-8
Rusmiati I, Husain DR, Alam G. Bioaktifitas
Ekstrak Methanol Daun Muda Sirsak Annona
muricata L. Sebagai Anti Bakteri Terhadap
staphylococcus aureus dan propioni bacterium
agnes. Universitas Hasanuddin, 2015:2-3
WHO. Research Guidelines for Evaluating The
Safety and Efficacy of Herbal Medicines.
Manila: World Health Organization Regional
Office for The Western Pacific, 1993:35.
17. Mukhriani, Faridha YN, Sitti M. Analisis
Kadar Flavonoid Total Pada Ekstrak Daun
Sirsak (Annona Muricata) Dengan Metode
Spektrofotometri UV-VIS.JF FIK UINAM,
2015;3 (2):37
18. Munish G. Effect of phyllanthusurinaria in
biochemical profile of experimental
hyperglycemic albino rats. Research Journal of
Pharmaceutical,2012; 1:2-6
19. Lelly Y, Miranti KD, Uci AL, Tryando B.
Potensi Ekstrak Air Daun Sirsak Sebagai
Penurun Kolesterol dan Pengendali Bobot
Badan. Jurnal Fakultas Kedokteran Hewan
IPB,2016;4 (2):82-87
20. Faris AM, Reza H, Zainul F. Pengaruh
Pemberian Minyak Atsiri Daun Sirsak (Annona
muricata) secara subkronik terhadap kadar
MDA Jaringan Aorta dan Ketebalan Dinding
Aorta pada Tikus Wistar. Jurnal FK UIM,
2018:1-8
21. Wulandari RL, Susilowati S, Amelya S.
Pengaruh Kombinasi Ekstrak Etanol Daun
Sirsak dan Gemfibrozil Terhadap Kadar
Trigliserida dan HDL Tikus yang diinduksi
Pakan Tinggi Lemak. Fakultas Farmasi
Universitas Wahid Hasyim Semarang,
2015:78-84
22. Tugianty E, Soegong H, Afduha NS. Pengaruh
Tepung Daun Sirsak Terhadap Karakteristik
Lemak Darah dan Daging Itik Tegal Jantan.
Universitas Wiayakusuma, 2016;40(3):214-216