ANTIDIABETES EFFECT OF NONI FRUIT(Morinda citrifolia L.

) ON
MICE WITH ORAL GLUCOSE TOLERANCE METHOD AND
STREPTOZOTOCIN INDUCTION METHOD
Nikeherpianti Lolok1,2, I. Sahidin3, Sri Adi Sumiwi1, Ahmad Muhtadi1
1
Faculty of Pharmacy, Universitas Padjadjaran, Indonesia
2
Faculty of Pharmacy, Mandala Waluya, Health Science Academy, Indonesia
3
Faculty of Pharmacy, Halu Oleo University, Indonesia
*Corresponding Author E-mail: nikeherpianti.apt@gmail.com

ABSTRACT :
Diabetes mellitus (DM) is a problem that deserves attention because of its increasing prevalence every year. The
prevalence of DM based on WHO in 2030 is predicted to reach 366 patients. Epidemiologically, it is estimated that
in 2030 the prevalence of DM in Indonesia reaches 21.3 million people. The purpose of this study was to determine
the effectiveness of glycosides from noni fruit on reducing blood sugar levels in normal rats induced by diabetes by
the method of glucose tolerance and induction of streptozotocin (STZ). Antidiabetic effect testing was divided into 8
groups namely 4 groups for oral glucose tolerance test in male mice (positive control group, negative control group,
glycoside control group, and normal group), 4 other groups for testing with STZ induction (positive control group,
positive control group, negative control, glycoside control group, and normal group). Oral glucose tolerance test
results on normal mice showed that glycosides from noni fruit (Morinda citrifolia L.) gave significantly different
results with negative controls at minute 30 ie 0.036 (p <0.05) and were not significantly different from positive
controls (0.462) subsequently at 120 minutes the results showed that the glycoside group was significantly different
from the negative group (0.028) and not significantly different from the positive group (0.261). Tests with STZ
induction method showed that the decrease in the level of blood sugar induced by the glycoside group was not
significantly different (p> 0.05) with the positive group on day 1 (0.056), day 3 (0.168), and day 7 (0.141) so that it
could be concluded that the glycosides from Noni fruit with a dose of 150 mg / kg body weight provides antidiabetic
activity.

KEYWORDS: Glycosides, Morinda citrifolia, Diabetes mellitus, Oral glucose tolerance,

Streptozotocin (STZ).

INTRODUCTION (Chattopadhyay, 2009). This patient safety factor is a

consideration for finding alternatives in dealing with
The threat of Diabetes Mellitus (DM) in the midst of DM from natural ingredients. The use of medicinal
people's lives is a very frightening specter because plants and phytochemicals to treat DM is to look for
almost every 10 seconds in the world people die due safer alternatives as medicines, which temporarily
to complications from the disease. DM is a chronic reduce blood glucose, prevent heart disease and high
disease that occurs when the body cannot produce blood pressure, and also improve antioxidant
enough insulin or when the body does not use insulin systems, insulin action and secretion (Vinayagam and
effectively which results in a metabolic disease Xu, 2015).
characterized by chronic hyperglycemia and
abnormalities in carbohydrate, protein, and fat The prospect of using natural products to treat DM
metabolism (WHO, 2015). has not been much studied. One of the medicinal
plants used to reduce blood glucose levels is noni (M.
One of the goals of therapy for patients with DM is citrifolia L). Noni (M. citrifolia L.) contains
controlling blood sugar levels by administering oral polysaccharides, glycosides, flavonoids, iridoids,
hypoglycemic drugs or exogenous insulin. carotinoids, and anthraquinones (Sogandi, 2019).
Pharmacological therapy of DM is generally given in Flavonoids that function as antioxidants are able to
the long term so that this can increase the risk of side withstand the rate of absorption of blood glucose
effects from medications such as hypoglycemia, liver from the digestive tract to blood vessels so that they
and kidney damage, psychonia, and lactic acidosis are able to withstand the rate of increase in blood
glucose levels (Suhartono et al, 2005). Flavonoids are Group I :Negative Control (Na. CMC 1%)
divided into 5 sub-classes including flavons, Group II :Positive Control (Glibenclamide 5 mg /
flavonols, flavonons, isoflavons, and anthocyanins kg BW)
(Arts et al., 2005). The sub-class of flavonols is Group III :Extract Control (Noni glycosides 150 mg
subdivided, one of which consists of quercetin / kgBW)
compounds. Several studies have focused on Group IV :Normal control (sufficient food and
quercetin to be developed as an antidiabetic drug to drink)
prevent and manage DM.
Diabetes Induction Test in Animal Mice
Previous studies have reported quercetin mechanisms Test animals are divided into 4 groups, consisting of :
in DM cases, such as decreased lipid peroxidation, Group 1 :Negative Control (Na. CMC 1%)
increased antioxidant enzymes (SOD, GPX, and Group 2 :Positive Control (Exogenous Insulin)
CAT), reduced glucose absorption in the intestine by Group 3 :Extract Control (Noni glycosides 150 mg
inhibiting GLUT2 (Coskun et al., 2005; Stewart et / kgBW)
al., 2009) . Research conducted by Kwon et al, Group 4 :Normal control (sufficient food and
(2007) explained that the transport of fructose and drink)
glucose by GLUT2 is strongly inhibited by quercetin.
Tested Procedure for Oral Glucose Tolerance
MATERIALS AND METHODS Method
Separation of Natural Compounds On the first day before treatment all treatment groups
Separation of glycoside compounds was carried out were fasted for 20 hours. After 20 hours blood sugar
by the process of extraction of the sympathetic by levels were measured from each group. Then each
maceration method to obtain maserate. Maserate is treatment group was induced by glucose orally, then
obtained thickened using a rotary evaporator, then the blood glucose levels were measured again in the 30th
thick extract is added with ethyl acetate to separate minute. Furthermore, they are given treatment
the glycosides from the Morinda citrifolia L. extract according to their respective groups. Blood sugar
with the partitioning process, the glycosides from the levels were measured at 0, 30, 60, 90, 120, 150, 180
Noni fruit will be at the bottom and the top is the minutes.
ethyl extract layer. acetate. The separated glycosides
are then thickened. STZ Induction Method Tested Procedure
On the first day before treatment all rats were fasted
Tested Animal Conditioning for 20 hours, then their fasting blood sugar levels
The experimental animals used in this study were were examined. Induction of diabetes in experimental
Wistar strain male mice aged 8 weeks and weighed animals is done by giving STZ (45 mg / kg BW)
between 20-30 g and placed in separate cages intraperitoneally. Blood sugar levels of mice were
according to the test group. The animals were checked again on the second day, 24 hours after STZ
adapted in the experimental cage one week before injection. Mice are declared diabetic if they have
being treated. The state of the cage is maintained at a glucose levels of 200-260 mg / dL, but this did not
temperature of 28-32 ° C and a dark-light cycle of 12 happen in this study which can be caused by several
hours each. Experimental animals were fed standard factors including lowering fasting blood sugar levels
diet pellets and ad libitum drinking water of experimental animals or the level of stress
(Sornalakshmi et al., 2016; Suresha et al., 2012). The experienced by experimental animals (Anitha et al. .,
total volume of administration is 1 ml which is the 2012; Sornalakshmi et al., 2016). After that, the test
volume that can be given based on the normal animals are given treatment according to their
volume of the stomach of mice (Ngatidjan, 2006). respective groups.

In this test the test animals were divided into 8 Data Analysis
groups, 4 groups for the oral glucose tolerance test The results of the study are expressed as mean ±
and 4 groups for the test in STZ induced mice. Each SEM. The significance of the data was analyzed by
group consists of 3 mice. One-way Analysis of Variance (ANOVA) (SPSS
16.0 program) with post hoc LSD's test. Data is
Glucose Tolerance Test in Animal mice considered significant if the p value is ≤ 0.05.
Test animals are divided into 4 groups, consisting of :
RESULTS AND DISCUSSION
RESULT :
Figure 1. Glucose-Induced Blood Sugar Level Diagram of Mice
350
300
250
200
150
100
50
0
KGDP KGDSIG 0 30 60 90 120 150 180

Kontrol Negatif Kontrol Normal

Kontrol Glikosida Kontrol Positif

Ket. : KGDP : Blood glucose level during fasting (mg / dL)

KGDG : Blood glucose Level After induced Glucose (mg / dL)
0 : Blood glucose Level after Treatment at 0 minute (mg / dL)
30 : Blood glucose Level after Treatment at 30 minute (mg / dL)
60 : Blood glucose Level after Treatment at 60 minute (mg / dL)
90 : Blood glucose Level after Treatment at 90 minute (mg / dL)
120 : Blood glucose Level after Treatment at 120 minute (mg / dL)
150 : Blood glucose Level after Treatment at 150 minute (mg / dL)
180 : Blood glucose Level after Treatment at 180 minute (mg / dL)

Figure 2. STZ Induced Blood Sugar Level Diagram of Mice

STREPTOZOTOCIN INDUCTION OBSERVATION TABLE

600
500
400
300
200
100
0
KGDP KGDSISTZ Hari ke-1 Hari ke-3 Hari ke-7

Kontrol Positif Kontrol Negatif Kontrol Normal Kontrol Glikosid

Ket. : KGDP : Blood glucose level during fasting (mg / dL)

KGDSISTZ : Blood glucose Level 24 hours after STZ Induction (mg / dL)
H+1 : Blood glucose Levels H + 1 Treatment (mg / dL)
H+3 : Blood glucose Levels H + 3 Treatment (mg / dL)
H+7 : Blood glucose Levels H + 7 Treatment (mg / dL)

DISCUSSION normally distributed. The analysis shows that there is

Normality test carried out on each treatment group no real difference. Statistical results on the oral
after giving glucose and after treatment minutes 0, glucose induction showed that the blood sugar levels
30, 60, 90, 120, 150, and 180 using the Shapiro-Wilk induced by the glycoside group to the negative and
test, showed that at all times the treatment data was positive groups were not significantly different (p>
0.05) with significant values of 0.036 and 0.462,
respectively, this proved that all induced decrease in blood sugar levels from induced blood
experimental animals had hyperglycemia, differing sugar levels.
the case with the normal group without glucose The results of this study indicate that glycosides
induction showed significant results in the negative which are the largest constituent of the components
group, positive group, and glycoside group. This is of the metabolite compounds in noni fruit provide
also in line with the statistical results of the induction effectiveness for healthy animals and diabetes.
of blood sugar levels in the STZ group.
CONCLUSIONS
This research aims to look at antidiabetic activity in Based on the results of the study after statistical
mice test animals with 2 methods namely to prove analysis and discussion, it can be concluded that:
that glycoside compounds from noni fruit can act as 1. Glycosides at a dose of 150 mg / kg BW from
antidiabetic in diabtes model animals and normal test noni extract (Morinda citrifolia L.) showed
animals. From the results it can be concluded that the antidiabetic activity in test animals with oral
glycoside compound testing using the oral glucose glucose tolerance test methods and were not
tolerance test method provides an optimal significantly different from positive control
antidiabetic effect by proving that the measurement activities.
of blood glucose levels decreased blood sugar levels 2. Glycosides at a dose of 150 mg / kg BW from
by 20.03% and positive control by 49.62%. This is noni extract (Morinda citrifolia L.) showed
also supported by statistical data based on the post antidiabetic activity in test animals using STZ
hoc test ie at the 30th minute, the decrease in blood induction method and not significantly different
sugar levels of the glycoside group (0.716) was not from positive control activities.
significantly different (p> 0.05) with the positive
group (0.490) while the negative control group
showed a significant result of 0.032. ACKNOWLEDGEMENT
This research above, in line with some previous The authors wish to express gratitude to STIKES
studies where it is said that the compounds contained Mandala Waluya for support to implementing this
in noni fruit have antidiabetic properties. The study
compounds contained in noni are ursolic acid
(triterpenoids); caprylic acid and hexanoic acid (fatty
acid); niacin; asperulosidic acid (iridoids); routine
CONFLICT OF INTERESTS
and quercetin (flavonoids); 2,6-di-O- (β-D12 There are no conflicts of interest.
glucopyranosyl 1-O-octanoil-β-D glucopyranose
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