Aktivitas Antidiabetes dari Senyawa Alfa Mangostin dari Kulit Buah Manggis

7/23/2019 Aktivitas Antidiabetes dari Senyawa Alfa Mangostin dari Kulit Buah Manggis

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Study Of α-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

bPenelitian Aktivitas Kimiawi Tumbuhan (PAKTI) Group, Chemistry Departement, Faculty of Mathematic and

Science, Institut Teknologi Sepuluh Nopember

*Corresponding author, email: [email protected]

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 onan information, mangostin has an antidiabetic bioactivity, but there are not any data that support this

information. Therefore, this research is required to obtained α-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 inducediabetes. This resulted in significant increase in blood glucose level. The diabetic and normal rat were bothrandomly 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 α-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 α-mangostin were compared with standard glibenclamide.

The findings of the study support the antidiabetic claims of α-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 aslightly acid and sweet flavor 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 amedicinal 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 againstinflammation and diarrhea, and cholera and dysentery (Chaverry, 2008). It has been a lot of data fromresearch results showing that G. mangostana has a wide range of bioactivity that can be used in thehealth and medicine related, among others, as antiproliferasi (Moongkarndi P, 2004), anti-bacterial(Suksamrarn S, 2003), anticancer (Huang, 2002), anti-HIV (Vlietinck, 1998) , inhibit oxidation ofLow 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 anantidiabetic, but there is still no research data to support this information (25 Mangostin NaturalMiracles). On the other hand, the source of information about the condition of society in Indonesiashowed that in 2000 an estimated 150 million people worldwide have diabetes mellitus. This amountis 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 inManado 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 2005expected to reach 12 million diabetic patients. Although Diabetes Mellitus (DM) is a chronic diseasethat 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 (DepkesRI, 2005). One part of the culture of Indonesia relating to the utilization of natural wealth, that is for

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health care and disease treatment. Cultures were obtained from the experience of generations. Variouskinds 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 beused up to now. As the times are more sophisticated today, the use of traditional medicines inIndonesia progress very rapidly. Advances in technology are increasingly sophisticated can treattraditional medicine more practice, comfortable and attractive. Many people assumes that traditionalmedicine can be used as an alternative treatment in addition to modern medicine.

Through the time, traditional medicine has developed an ever increasing, especially with theemergence 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 saferthan synthetic drugs. However it does not mean traditional medicine has no adverse side effects. Keepin 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. Soincorrect, to say that traditional medicines have no side effects, no matter how small the side effectsremain, 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 ofnatural resource that have been through separation and purification processes that have beendetermined 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 nodata can support this information, then this paper are study about isolation proccess and bioactivitytest of antidiabetic α-mangostin compounds from fruit hull G. mangostana.

MATERIAL AND METHODS

Plant material: Fresh fruits of Garcinia mangostana were collected in sufficient quantity fromJakarta. Pericarp of this fruits separated from these pulp, and carefully washed with tap water toremove 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 atroom temperature to obtain solid sample. The hexane extract was treated with chromatography

method to obtained α-mangostin compound.

Animals: Healthy male Wistar rats (150-200 g) were obtained from the animal house of the Facultyof Pharmacy, Airlangga University, Surabaya. The animal were housed under normal laboratorycondition of humidity temperature and light. They were allowed free access to drinking water andanimal pellet.

Induction of diabetes mellitus: Diabetes mellitus was induced in overnight fasted adult male Wistarrats weighing 150–200 g by a single intraperitoneal injection of 120mg/kg alloxan monohydrate.

Hyperglycemia was confirmed by the elevated glucose levels determined at 72 h. Animals with bloodglucose level more than 150mg/dl were considered as diabetic. Rats found with permanent diabeteswere used for the antidiabetic study. This model has been used in earlier studies to induce type IIdiabetes 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 α-mangostin (at doses 10 mg/kg);

Group D: Diabetic rats administered α-mangostin (at doses 30 mg/kg);

Group E: Diabetic rats administered α-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 24h 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 177-178oC that known as α-mangostin. Antidiabetic assay of this compound give

positive result have anti-hyperglicemic effect in alloxan-diabetic rats. As shown in Table 1, there wasa sharp increase in blood glucose level of the rats after treatment with alloxan. This increase was

reversed after treated with α-mangostin, as shown in Table 2.

Table 1: Effect of α-mangostin on blood glucose level in alloxan (120mg/kg b.w.) induced diabetic

rats.

Group n=5Blood glucose before

induction (mg/dL)

Blood glucose after

induction (mg/dL)

A (Negative control) 67±4.5 97.2±7.7

B (Positive control) 70±4.9 264±204

C (10 mg/kg α-mangostin) 72.2±7.1 161.6±42.8

D (30 mg/kg α-mangostin) 67.6±12.8 367.4±146.1

E (50 mg/kg α-mangostin) 67.4±8.2 155±39.4

F (10 mg/kg glibenclamide) 79.2±6.7 132±20.8

Table 1: Effect of α-mangostin on blood glucose level in alloxan induced diabetic rats

Group n=5Blood glucose before α-

mangostin (mg/dL)

Blood glucose after

α-mangostin (mg/dL)

A (Negative control) 97.2±7.7 99.8±9.4

B (Positive control) 264±204 291±137.9

C (10 mg/kg α-mangostin) 161.6±42.8 102.4±15.9

D (30 mg/kg α-mangostin) 367.4±146.1 272±119.9*

E (50 mg/kg α-mangostin) 155±39.4 112±28.9

F (10 mg/kg glibenclamide) 132±20.8 80.4±14.1

Each value represent Mean±Sd. *Pvalue < 0.05 compared with control

The most significant antidiabetic activity was observed with α-mangostin at dose level of 30 mg/kg

i.p.The result presented in Table 2 shows that 30 mg/kg α-mangostin reduced blood glucose from367.4±146.1 to 272±119.9 (Pvalue < 0.05). While comparing with the diabetic control, the reduction in

blood glucose by 30 mg/kg of α-mangostin in diabetic rats were statistically significant.

Discussion: From the result obtained in this study, α-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 theadministration of 30 mg/kg α-mangostin reduced blood glucose from 367.4±146.1 to 272±119.9. The

decrease in blood glucose produce by α-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 α-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 α-tocopherol consumption induced by LDL oxidation. Consistently,Mahabusarakam et al. (2000) also found that α-mangostin and their synthetic derivatives prevent the



decrease of the α-tocopherol consumption induced by LDL oxidation. These authors found that the

structural modifications of α-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 butsignificant non-enzymatic glycosylation of proteins in diabetes. Glucose auto-oxidise in the presenceof 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 isevidence 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 specific 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 defined as “any substance, when present at low concentrationscompared with that of an oxidizable substrate, that significantly delays or prevents oxidations of thatsubstrate”. 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 anddietary antioxidants (Govindarajan, 2005).

Induction of diabetes in rats with streptozotocin (STZ) or alloxan uniformly results in anincrease in thiobarbituric acid reactive substances (TBARS), an indirect evidence of intensified free-radical production. Preventing the formation of hydroxyl radicals would be an efficient means to

reduce hydroxyl-induced damage, and several compounds have been tested as antioxidants in diabeticanimals with varying success. For example, the increase in TBARS associated with diabetes is prevented by treatment with nicotinamide, boldine, melatonin, aspirin, L-arginine or sodiumnitroprusside, probucol, L-lipoic acid, aminoguanidine, captopril, enalapril, or nitecapone, if thistreatment is given before or immediately after the diabetogen (Maritim, 2002).

Recently, the consumption of Mangosteen products has increased as a d ietary supplement inthe United States, because of their potent antioxidant properties (Jung et al., 2006). A study byWilliams, et al. (1994) showed that 100 μM of mangostin inhibited TBARS production by about 20%.The possible mechanism action of α-mangostin may be perform by substitution hydroxyl group as afree radical scavenging that are as reductant and can act as a donor of hydrogen to free radicals.

CONCLUSION

In conclusion, this study showed that α-mangostin compound from fruit hull G. mangostana

possesses hypoglycemic properties and it may prove to be effective for the treatment of DiabetesMellitus. However, longer duration studies on c hronic models are necessary to elucidate the exactmechanism 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 financial

assistance in carrying out this study.



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Aktivitas Antidiabetes dari Senyawa Alfa Mangostin dari Kulit Buah Manggis

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