Study Of -Mangostin Compound And Antidiabetic Assay From

Fruit Hull Of Garcinia Mangostana Linn.

Devyana Dyah Wulandari,1* Taslim Ersam
a

Postgraduate Program in Chemistry Departement, Faculty of Mathematic and Science, Institut Teknologi
Sepuluh Nopember

Penelitian Aktivitas Kimiawi Tumbuhan (PAKTI) Group, Chemistry Departement, Faculty of Mathematic and
Science, Institut Teknologi Sepuluh Nopember
*Corresponding author, email: paktichem@gmail.com
Abstract. Garcinia mangostana Linn. is known as the queen of fruits because it is one of the best tasting tropical
fruits. The mangostin-fruit has been used as a m edicinal agent, such as antioxidant, antiproliferasi,
antibacterial agent, anticancer, anti HIV, decreases the human low density lipoproteins (LDL) oxidation,
induced apoptosis in human leukemia cell lines, anti hypertensive, anti malaria, and many others. Based on
an information, mangostin has an antidiabetic bioactivity, but there are not any data that support this
information. Therefore, this research is required to obtained -mangostin compounds, and antidiabetic
bioactivity assay contained in fruit hull G. mangostana. Antidiabetic activity was investigated in normal
and diabetic rat. Animals were treated intraperitoneally with a single dose of 120 mg/kg alloxan to induce
diabetes. This resulted in significant increase in blood glucose level. The diabetic and normal rat were both
randomly divided into 6 group. Group A (negative control) received distilled water ad libitum. Group B
(positive control) were treated intraperitoneally with single dose of 120 mg/kg alloxan. Group C, D, and E
were treated intraperitoneally with single dose of 10, 30, and 50 mg/kg -mangostin. Group F received 10
mg/kg glibenclamide for the same period. Blood glucose levels and changes in body weight were evaluated
in normal rats. The diabetic groups treated with -mangostin were compared with standard glibenclamide.
The ndings of the study support the antidiabetic claims of -mangostin.
Keywords: Garcinia mangostana Linn., xanthone, mangostin, antidiabetic.

INTRODUCTION
The mangosteen-fruit is dark purple or reddish, with white, soft and juicy edible pulp with a
slightly acid and sweet avor and a pleasant aroma. Mangosteen is known as the queen of fruits
because it is one of the best tasting tropical fruits. The pericarp of mangosteen-fruit has been used as a
medicinal agent by Southeast Asians for centuries in the treatment of skin infections and wounds,
amoebic dysentery, etc. In Ayurvedic medicine the pericarp of mangosteen-fruit has wide use against
inammation and diarrhea, and cholera and dysentery (Chaverry, 2008). It has been a lot of data from
research results showing that G. mangostana has a wide range of bioactivity that can be used in the
health and medicine related, among others, as antiproliferasi (Moongkarndi P, 2004), anti-bacterial
(Suksamrarn S, 2003), anticancer (Huang, 2002), anti-HIV (Vlietinck, 1998) , inhibit oxidation of
Low Density Lipoprotein (LDL) (Williams, 1995), induce apoptosis (Sato, 2004) anti-hypertensive
(Wang, 2002), anti-malarial (ignatushchenko, 1997) and there are many others.
In addition, from a source of information indicates that the G. mangostana has activity as an
antidiabetic, but there is still no research data to support this information (25 Mangostin Natural
Miracles). On the other hand, the source of information about the condition of society in Indonesia
showed that in 2000 an estimated 150 million people worldwide have diabetes mellitus. This amount
is expected to rise to double in 2005, and mostly, the increase will occur in developing countries such
as Indonesia. Population of diabetics in Indonesia is estimated to range between 1.5 to 2.5% except in
Manado 6%. With a population of around 200 million inhabitants, means approximately 3-5 million
people in Indonesia suffer from diabetes.
Recorded in 1995, the number of diabetics in Indonesia reached 5 million people. In 2005
expected to reach 12 million diabetic patients. Although Diabetes Mellitus (DM) is a chronic disease
that does not cause death directly, but can be fatal if not managed appropriately. The management of
DM requires a multidisciplinary treatment that includes non-drug therapy and drug therapy (Depkes
RI, 2005). One part of the culture of Indonesia relating to the utilization of natural wealth, that is for

health care and disease treatment. Cultures were obtained from the experience of generations. Various
kinds of plants in natural surroundings can provide health benefits for its consumers. Then continue to
be further developed and passed down through the generations, so that traditional medicine can be
used up to now. As the times are more sophisticated today, the use of traditional medicines in
Indonesia progress very rapidly. Advances in technology are increasingly sophisticated can treat
traditional medicine more practice, comfortable and attractive. Many people assumes that traditional
medicine can be used as an alternative treatment in addition to modern medicine.
Through the time, traditional medicine has developed an ever increasing, especially with the
emergence of the issue back to nature and a prolonged economic crisis that reduces people's
purchasing power. While many people assume that the use of traditional medicine is relatively safer
than synthetic drugs. However it does not mean traditional medicine has no adverse side effects. Keep
in mind that adequate information about the accuracy of dose, time of use, how to use, material
selection properly, selection of traditional medicine for specific indications for optimal use. So
incorrect, to say that traditional medicines have no side effects, no matter how small the side effects
remain, but it can be minimized if sufficient information is obtained (Katno, 2006).
Altough the traditional medicine is not a single active compound, the reaction was slow in the
body, but it is less reliable safe and cleanliness. It would require an active compound from extracts of
natural resource that have been through separation and purification processes that have been
determined pre-dose through clinical trials (to animal testing) to determine the doses level of security.
Based on the fruit hull G. mangostana has an activity as an antidiabetic agent and there are no
data can support this information, then this paper are study about isolation proccess and bioactivity
test of antidiabetic -mangostin compounds from fruit hull G. mangostana.
MATERIAL AND METHODS
Plant material: Fresh fruits of Garcinia mangostana were collected in sufficient quantity from
Jakarta. Pericarp of this fruits separated from these pulp, and carefully washed with tap water to
remove other foreign materials. They were then air-dried in open air and then the dry pericarp were
blended into a blender. The 1 kg of the powdered pericarp was weighed and extracted in hexane at
room temperature to obtain solid sample. The hexane extract was treated with chromatography
method to obtained -mangostin compound.
Animals: Healthy male Wistar rats (150-200 g) were obtained from the animal house of the Faculty
of Pharmacy, Airlangga University, Surabaya. The animal were housed under normal laboratory
condition of humidity temperature and light. They were allowed free access to drinking water and
animal pellet.
Induction of diabetes mellitus: Diabetes mellitus was induced in overnight fasted adult male Wistar
rats weighing 150200 g by a single intraperitoneal injection of 120mg/kg alloxan monohydrate.
Hyperglycemia was conrmed by the elevated glucose levels determined at 72 h. Animals with blood
glucose level more than 150mg/dl were considered as diabetic. Rats found with permanent diabetes
were used for the antidiabetic study. This model has been used in earlier studies to induce type II
diabetes in rats. Glibenclamide (10 mg/kg) was used as the standard drug.
Experimental procedure: Animals were divided into six groups, each consisting of 5 rats.
Group A: Normal control rats administered saline (0.9%, w/v);
Group B: Diabetic control rats administered saline (0.9%, w/v);
Group C: Diabetic rats administered -mangostin (at doses 10 mg/kg);
Group D: Diabetic rats administered -mangostin (at doses 30 mg/kg);
Group E: Diabetic rats administered -mangostin (at doses 50 mg/kg);
Group F: Diabetic rats administered glibenclamide (10 mg/kg);

All the drugs were administered intraperitoneally. Blood sample drawn from caudal vein of the rats 24
h after the last dose and blood glucose level was measured using On Call Plus Blood Glucose
Monitoring System.
RESULTS AND DISCUSSION
Result: The hexane extract was treated with chromatography method result a yellow powder with
melting point 177-178 oC that known as -mangostin. Antidiabetic assay of this compound give
positive result have anti-hyperglicemic effect in alloxan-diabetic rats. As shown in Table 1, there was
a sharp increase in blood glucose level of the rats after treatment with alloxan. This increase was
reversed after treated with -mangostin, as shown in Table 2.
Table 1: Effect of -mangostin on blood glucose level in alloxan (120mg/kg b.w.) induced diabetic
rats.
Blood glucose before Blood glucose after
Group n=5
induction (mg/dL)
induction (mg/dL)
A (Negative control)
674.5
97.27.7
B (Positive control)
704.9
264204
C (10 mg/kg -mangostin)
72.27.1
161.642.8
D (30 mg/kg -mangostin)
67.612.8
367.4146.1
E (50 mg/kg -mangostin)
67.48.2
15539.4
F (10 mg/kg glibenclamide)
79.26.7
13220.8
Table 1: Effect of -mangostin on blood glucose level in alloxan induced diabetic rats
Blood glucose before - Blood glucose after
Group n=5
mangostin (mg/dL)
-mangostin (mg/dL)
A (Negative control)
97.27.7
99.89.4
B (Positive control)
264204
291137.9
C (10 mg/kg -mangostin)
161.642.8
102.415.9
D (30 mg/kg -mangostin)
367.4146.1
272119.9*
E (50 mg/kg -mangostin)
15539.4
11228.9
F (10 mg/kg glibenclamide)
13220.8
80.414.1
Each value represent MeanSd. *Pvalue < 0.05 compared with control
The most signicant antidiabetic activity was observed with -mangostin at dose level of 30 mg/kg
i.p.The result presented in Table 2 shows that 30 mg/kg -mangostin reduced blood glucose from
367.4146.1 to 272119.9 (Pvalue < 0.05). While comparing with the diabetic control, the reduction in
blood glucose by 30 mg/kg of -mangostin in diabetic rats were statistically significant.
Discussion: From the result obtained in this study, -mangostin that it is a mayor compound from
fruit hull of G. mangostana produce a dose dependent decrease in blood glucose level of alloxan
diabetic rats. The observed reduction in blood glucose was statistically significant with the
administration of 30 mg/kg -mangostin reduced blood glucose from 367.4146.1 to 272119.9. The
decrease in blood glucose produce by -mangostin at dose range is also comparable to that produce by
glibenclamide, a standard hypoglycemic drug. Williams et al. (1995) found that a-mangostin
decreases the human low density lipoproteins (LDL) oxidation induced by copper or peroxyl radical
(Williams, 1995). They found that -mangostin (i) prolonged lag time of conjugated dienes at 234 nm
in a dose-dependent manner, (ii) diminishes thiobarbituric reactive substances (TBARS) production,
and (iii) decreases the -tocopherol consumption induced by LDL oxidation. Consistently,
Mahabusarakam et al. (2000) also found that -mangostin and their synthetic derivatives prevent the

decrease of the -tocopherol consumption induced by LDL oxidation. These authors found that the
structural modications of -mangostin modify the antioxidant activity. For example, substitution of
C-3 and C-6 with aminoethyl derivatives enhanced the activity; whereas substitution with methyl,
acetate, propanediol or nitrile reduced the antioxidant activity (Mahabusarakam et al., 2000).
It has been postulated that the etiology of the complications of diabetes involves oxidative
stress perhaps as a result of hypoglycemia. This glucose and hyperglycemia-related with increasing
protein glycosylation are important sources of free radicals. Elevated glucose causes slow but
signicant non-enzymatic glycosylation of proteins in diabetes. Glucose auto-oxidise in the presence
of transition metal ions generating oxygen free radicals, which make the membrane vulnerable to
oxidative damage. As the diabetogenic action can be prevented by the Superoxide dismutase (SOD),
Catalase (CAT), and other hydroxyl radical scavengers such as ethanol, dimethyl urea, there is
evidence to suggest that the incidence of diabetes involves superoxide anion and hydroxyl radicals
(Govindarajan, 2005).
Antioxidant agent is evident through the reactions of oxygen, that it is toxic; still only the
aerobes survive its presence, primarily because they have evolved an inbuilt antioxidant defense.
Antioxidant defenses comprise:
Agents that catalytically remove free radicals and other reactive species like SOD, CAT,
peroxidase and thio specic antioxidants.
Proteins that minimize the availability of peroxidase such as iron ions, copper ions and haem.
Proteins that protect biomolecules against oxidative damage example heat shock proteins.
Low molecular mass agents that scavenge ROS and RNS, example GSH, ascorbic acid,
tocopherol. The antioxidants may be dened as any substance, when present at low concentrations
compared with that of an oxidizable substrate, that signicantly delays or prevents oxidations of that
substrate. The term oxidizable substrate includes every type of molecule found in vivo. Antioxidant
defense include the antioxidant enzymes like SOD, CAT, GSH-px, etc, low molecular agents and
dietary antioxidants (Govindarajan, 2005).
Induction of diabetes in rats with streptozotocin (STZ) or alloxan uniformly results in an
increase in thiobarbituric acid reactive substances (TBARS), an indirect evidence of intensied freeradical production. Preventing the formation of hydroxyl radicals would be an efcient means to
reduce hydroxyl-induced damage, and several compounds have been tested as antioxidants in diabetic
animals with varying success. For example, the increase in TBARS associated with diabetes is
prevented by treatment with nicotinamide, boldine, melatonin, aspirin, L-arginine or sodium
nitroprusside, probucol, L-lipoic acid, aminoguanidine, captopril, enalapril, or nitecapone, if this
treatment is given before or immediately after the diabetogen (Maritim, 2002).
Recently, the consumption of Mangosteen products has increased as a d ietary supplement in
the United States, because of their potent antioxidant properties (Jung et al., 2006). A study by
Williams, et al. (1994) showed that 100 M of mangostin inhibited TBARS production by about 20%.
The possible mechanism action of -mangostin may be perform by substitution hydroxyl group as a
free radical scavenging that are as reductant and can act as a donor of hydrogen to free radicals.
CONCLUSION
In conclusion, this study showed that -mangostin compound from fruit hull G. mangostana
possesses hypoglycemic properties and it may prove to be effective for the treatment of Diabetes
Mellitus. However, longer duration studies on c hronic models are necessary to elucidate the exact
mechanism of action so as to develop it as a potent antidiabetic drug.
ACKNOWLEDGMENT
The authors sincerely thank Program Penelitian Guru Besar, Lembaga Penelitian dan Pengabdian
kepada Masyarakat (LPPM) Institut Teknologi Sepuluh Nopember, Surabaya for providing nancial
assistance in carrying out this study.

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