CHAPTER I INTRODUCTION A. Background Various diseases in the body caused by free radicals. Free radicals are atoms or groups which have one or more unpaired electrons. Free radicals are also found in the environment, some metals (eg iron and copper), cigarette smoke, drugs, packaged food, additives, and others (Droge, 2002). In protecting the body against free radicals, antioxidant substances serve to stabilize free radicals with a complete lack of electrons from free radicals that inhibit the chain reaction (Windono et al., 2001). According Windono et al. (2001), the antioxidant is a compound that can be used to protect foodstuffs by decelerating damage, rancidity, or discoloration caused by oxidation. Antioxidants are able to act as a hydrogen radical donor or acceptor can act as free radicals that can delay the initiation stage of the formation of free radicals. The presence of natural antioxidants (such as phenolic compounds) or synthetic, can inhibit lipid oxidation, prevent damage, alteration organic components in foodstuffs so that it can extend the shelf life (Rohdiana, 2001). Mangosteen is a fruit that is known to have many benefits in the treatment. Part of the mangosteen rind can be used as hypogycemic (antidiabetic effect, helps lower blood sugar) empirically. Traditionally the skin of the fruit is often used in traditional medicine such as diarrhea, dysentery, eczema and other skin diseases. Mangosteen (Garcinia mangostana L.) is a plant originating from the region of Southeast Asia including Indonesia, Malaysia, Thailand and Myanmar. Mangosteen is a functional plants because most of these plants can be used as a drug. However, many do not know if the mangosteen rind has efficacy. The skin of the mangosteen fruit that had been discarded as waste after it is eating the meat of fruit, it has a myriad of important benefits for health. In the skin of the mangosteen fruit is rich in antioxidants such as xanthones and anthocyanins (Moongkandi, et al., 2004; Kristenses, 2005; Weecharangsan, et al., 2006; Hartanto 2011). In addition, some studies have also shown that the skin of the mangosteen fruit (Garcinia mangostana L.) contain compounds that have pharmacological activity and antioxidant. Such compounds including flavonoids, tannins and xanton (Ho et al., 2002; Jung et al., 2006; Moongkandi et al., 2004; Weecharangsan et al., 2006). B. Problem Formulation Based on the above it appears some problems such as: What is mangosteen fruit? How extraction methods mangosteen rind? How pharmacology and antioxidant activity of the extract of mangosteen rind? C. Purpose The purpose of this paper is: 1. To find out what the mangosteen fruit. 2. ffor know how extraction methods mangosteen rind. 3. To determine the pharmacological and antioxidant activity of extracts of mangosteen rind.
CHAPTER II LITERATURE REVIEW A. Description Mangosteen (Garcinia mangostana L.) 1. Plant Systematics Mangosteen (Garcinia mangostana L.) Division: Spermatophyta Subdivision: Angiospermae Class: Dicotyledonae Order: Guttiferanaless Family: Guttiferae Genus: Garcinia Species: Garcinia mangostana L. (Rukmana, 1995) 2. Region name Manggis is called by various names such as Manggu local (West Java), Manggus (Lampung), manggusto (North Sulawesi), manggista (West Sumatra) (Anonymous, 2000). 3. Morphology Mangosteen including annual crops (perennial) that its life can reach tens of years. Rod-shaped mangosteen trees, woody, growing straight up until it reaches a height of 25 meters or more. The bark is rough and brownish. Branching plants are generally symmetrical form a canopy of lush and shady like a pyramid. Mangosteen leaves are round to oval-egg-length, single and short-stemmed growth once without Stipule (stipulae). The structure of the leaf blade is thick with upper surface shiny green, while the lower surface yellowish green color (Rukmana, 1995). 4. Chemical Ingredients According to research Jung et al. (2006) and Suksamran et al. (2002) the main component contained in the skin of the mangosteen fruit is xanton. Xanton is a compound composed of a tricyclic aromatic rings substituted with an assortment of phenolic groups, methoxy, and isoprene (Walker, 2007). Bark, fruit, and dried latex contains a number of Garcinia mangostana L. yellow dye derived from two metabolites that mangostin and β-mangostin (Sudarsono et al., 2002). Xanton other derivative compound is 9-hydroxycalabaxanthone, 3-isomangostin, gartanin, 8- desoxygartanin (Walker, 2007), γ-mangostin and methoxy-β- mangostin (Akao et al., 2008). The compound α-mangostin the compound is mostly found in the skin of the mangosteen fruit (Jung et al., 2006). Xanton chemical structure and its derivatives (Walker, 2007) 5. Benefits Plant According to Sudarsono et al., (2002) the mangosteen fruit is used to treat diarrhea, inflammation of the tonsils, vaginal discharge, dysentery, hemorrhoids, ulcers and toothache. Skin of the fruit is used to treat ulcers, dysentery, sore muscles, constipation. Methanol extract of mangosteen rind has the effect antiploriferatif and potent antioxidants (Moongkarndi et al, 2004). Xanton compounds contained in the skin of the mangosteen fruit can inhibit the growth of breast cancer cells, epidermoid carcinoma, small cell lung cancer and hepatocellular carcinoma (Obolskiy et al., 2009). Xanton compounds in the skin of the mangosteen fruit can inhibit the growth of colon cancer cells DLD-1 with IC50 values methoxy-β-mangostin & lt; β-mangostin & lt; α-mangostin & lt; γ-mangostin (Akao et al, 2008). The study by Matsumoto et al (2003) suggest that α-mangostin contained in mangosteen rind has a 6 antiploriferatif activity against HL60 leukemia cells by inducing apoptosis. According to research Jung et al. (2006), α-mangostin has antibacterial activity against Mycobacterium tuberculosis with IC50 values of 6.25 ug / ml, and have antioxidant activity with IC50 value of 1.0 ug / ml. B. The compound α-α-mangostin mangostin compound is the compound is mostly found in the skin of the mangosteen fruit (Figure 2). The compound α-mangostin an amorphous yellow crystals which have a melting point 180-182oC. Uptake was high in the UV region at wavelengths of 215, 243 and 317 nm (Ee et al., 2005). The compound α-mangostin tend to be non-polar, so it will be easily dissolved in solvents which are non polar, such as hexane (Walker, 2007). The chemical structure of α-mangostin (Walker, 2007) Assay of α-mangostin can be done using TLC and HPLC. Methods TLC using chloroform mobile phase: ethyl acetate: methanol (80: 10: 5), with a stationary phase silica gel 60F245, UV detection at 366 nm and obtained α-mangostin HRF price amounting to 50.0 (Pothitirat and Gritsanapan, 2008). HPLC method using a mobile phase of 0.1% phosphoric acid: acetonitrile with C18 stationary phase (Pothitirat and Gritsanapan, 2009). Research that has been conducted Walker (2007) by the HPLC method using a mobile phase of methanol: 0.1% formic acid in water (75:25) can separate compounds xanton compound found in mangosteen. C. Forms of preparations Herbal preparations are preparations herbal traditional medicine made in a simple manner such as infusion, decoction, and in part derived from botanicals. Simplicia is a natural substance in the form of a whole plant, plant part or exudates of plants used as medicine, and has not undergone processing in a simple and yet a pure substance unless otherwise stated, in the form of material that has dried (MOH, 2000). The dosage forms of medicinal plants that have long been used, among others: 1. infuse infusion is a liquid preparation made with quote simplisia vegetable with water at a temperature of 90 ° C for 15 minutes (MOH RI, 1979). Infundation is penyarian process that is generally used to sum up the content of the active substance is soluble in water than plant-based ingredients (MOH, 1986). Making infuse the simplest way to make a herbal preparation of soft material such as leaves and flowers (MOH RI, 2000). 2. decoction decoction is a liquid preparation made by extracting herbal preparations with water at a temperature of 90 ° C for 30 minutes (MOH RI, 2000). 3. Making preparations tea tea for medicinal purposes as much done based on the experience in the manufacture of infusion were performed on black tea as a beverage (MOH RI, 2000). Some things need to be considered in the preparation of tea are: the number of bulbs and water, and the degree of fineness simplisia. Total crude drug dose expressed in grams and water in ml dose. While the degree of gloss to the wood, bark and roots chopped a bit rough with a size of approximately 2.5 mm (MOH RI, 2000). CHAPTER III DISCUSSION A. Definition Mangosteen Fruit Mangosteen (Garcinia mangostana L.) is a plant originating from the region of Southeast Asia including Indonesia, Malaysia, Thailand and Myanmar. Mangosteen is a functional plants because most of these plants can be used as a drug. However, many do not know if the mangosteen rind has efficacy. The skin of the mangosteen fruit that had been discarded as waste after it is eating the meat of fruit, it has a myriad of important benefits for health. In the skin of the mangosteen fruit is rich in antioxidants such as xanthones and anthocyanins (Moongkandi, et al., 2004; Kristenses, 2005; Weecharangsan, et al., 2006; Hartanto 2011). The mangosteen fruit is round and dark purple color because it contains a lot of anthocyanins in the skin (Obolskiy et al., 2009). In the fruit pulp are 5-6. Have 1-3 seeds, seed membrane thick juicy, white and edible. Mangosteen tree has a root fibers. On the following pages viewable image of the mangosteen fruit crops. The skin of the mangosteen fruit contains compounds that have pharmacological activity as anti-inflammatory, antihistamine, antibacterial, antifungal, cancer, hypertension, stroke and HIV therapy. Some of the main compounds of the content of mangosteen rind has a class of pharmacological activity xanton (Nugroho, 2009). Besides According Polytechnic full education website competition (2010), mangosteen rind is also used to treat ulcers, dysentery, sore muscles, constipation, and even Anti-fatigue (energize), Anti-oxidant (removing toxins from the body), Anti-seborrheaic (menpercantik skin), Anti-obesity (to lose weight), Anti-glaucomic (sore eye / glaucoma). B. Methods of Extraction The extraction process is done by stopping the enzyme activity in plant tissue beforehand to prevent oxidation or hydrolysis enzyme (Harborne, 1987). Extraction activity in the form of withdrawal of chemical compounds that can dissolve so that apart from the insoluble material with a liquid solvent. By knowing the active compounds contained in crude drugs would facilitate the choice of solvent and extraction right (DITJEN POM, 2000). Making extract in this study using maceration method. Maceration can be done by including 10 parts simplisia with degrees delicate that fit into the vessel, covered with 75 parts liquid penyari, closed, left for 5 days protected from light while stirring often, serkai, wring it out, wash the pulp with liquid penyari sufficient to obtain 100 part. Move into the closed vessel, leave in a cool place, protected from light, for 2 days. Enap pour or strain (Pharmacopoeia, 1979). C. Pharmacological Activities And Antioxidants Utilization mangosteen rind has actually been done long ago. The skin of the mangosteen fruit is traditionally used on a variety of treatment in the State of India, Sri rare Myanmar, and Thailand (Mahabusarakam et al., 1987). Broadly, the Thai people take advantage of mangosteen rind for the treatment of canker sores, dysentery, cystitis, diarrhea, gonorrhea, and eczema (ICUC, 2003). In the modern era, the use of mangosteen kuliat widely in the country sparked the interest of scientists for investigating and developing lembih keberkhasiatan further scientific aspects of the mangosteen rind. Many studies have proven the efficacy of mangosteen rind, and are even finding compounds that are responsible for these effects. The following will be presented a discussion of the pharmacological effects of mangosteen rind. 1. Activities antihistamine in allergic reactions, the main component of which took Beran important mast cells, and their mediators, namely the release of histamine and serotonin. Allergies are caused by the immune response to an antigen or allergen interacts with B lymphocytes to produce immunoglobulin E (IgE). Imunoglubulin E produced then attaches itself to the receptor FcεRI on the surface of mast cell membrane. Upon their return interaction between antigen-antibody, will stimulate mast cells to release histamine (Kresno, 2001; Subowo, 1993). Associated with allergic reactions or the release of histamine, Chairungsrilerd et al. (1996a, 1996b, 1998) to test the methanol extract of mangosteen rind to the contraction of isolated rabbit aorta chest induced by histamine and serotonin. From the analysis of the active components of the result of the continued fraction silica gel chromatography, indicating that the active compound is alpha and gamma mangostin. Alpha mangostin itself able to demonstrate the inhibitory activity contracted guinea pig isolated trachea and aorta piston isolated rabbit, induced cimetidine, histamine H2 receptor antagonists. However, these compounds do not show activity on the contraction induced karbakol, phenylephrine and KCl. Alpha mangostin was also able to inhibit binding of [3H] mepyramine against arta smooth muscle cells of rats. The latter compound is a specific antagonist for histamine H1 receptor. From the analysis of the kinetics of binding of [3H] mepyramine megnindikasikan that competitively inhibit alpha mangostin. This study suggests that alpha-mangostin is categorized as any blocks H1 receptors histaminergik particular, while gamma mangostin as any blocks serotonergic receptors, especially the 5-hydroxytryptamine 2A or 5HT2A. Furthermore, Nakatani et al. (2002a) conducted research into the mechanism toward the mangosteen rind extract. In the study of mangosteen peel extract is: 100% ethanol, 70%, 40%, and water, tested against prostaglandin E2 synthesis and release of histamine. 40% ethanol extract showed the most potent effect in inhibiting histamine release from RBL 2H3- cell-mediated IgE. All mangosteen rind extract capable of inhibiting the synthesis of PGE2 from rat glioma cells induced Ca2 + ionophore A23187. In the passive cutaneous anaphylaxis reaction, all of mangosteen peel extract also shows the inhibitory activity of the reaction. From this study, 40% ethanol extract of mangosteen is the most potent in inhibiting PGE2 synthesis and release of histamine. 2. Anti-inflammatory Activity Research on anti-inflammatory activity of mangosteen rind until now only performed on the stages of in vitro and in vivo to a new stage in the study with rats induced karagenen method. From the research results suggested that compounds that have anti-inflammatory activity is gamma-mangostin. Gamma-mangostin is xanton diprenilasi tetraoksigenasi form, the chemical structure can be seen in Fig. Nakatni et al. (2002b) conducted a study of anti-inflammatory activity in vitro of gamma mangostin against PGE2 synthesis and cyclooxygenase (COX) in rat C6 glioma cells. Both the compound and the enzyme is an important mediator in the inflammatory reaction. Gamma-mangostin potently inhibit the release of PGE2 in rat C6 glioma cells induced Ca2 + ionophore A23187. Gammamangostin inhibit the conversion of arachidonic acid to PGE2 in the microsomal, there is a possibility of cyclooxygenase inhibition on track. In experiments in vitro enzymatic, this compound is able to inhibit the activity of the enzyme COX-1 and COX-2. However, these compounds have no significant effect on: (1) phosphorylation signal ekstraseuler p42 / p44 induced A23187, which regulates activated protein kinase kinase / mitogen, and (2) release of [14C] arachidonic -asam of cells labeled [14C ] the Aa. From this study, gamma mangostin has anti-inflammatory activity by inhibiting the activity of cyclooxygenase (COX). Furthermore, Nakatani et al. (2004) analyzed the effect of gamma-mangostin against COX-2 gene expression in rat C6 glioma cells. Gamma mangostin inhibits protein and mRNA expression of COX-2 induced by lipopolysaccharide, but no effect on protein expression of COX-1. Lipopolysaccharide serves to stimulate phosphorylation inhibitor kappaB (IkappaB) mediated IkappaB kinase, which then further degradation and induces nuclear translocation of NF-kappaB ligand that activates gene transcription of COX-2. In connection with that, it also inhibits gamma mangostin IkappaB kinase activity and decreases degradation IkappaB and LPS-induced phosphorylation. In luciferase reporter assay, the compound lowering the NF-kappaB activation induced by LPS and the process of gene transcription of COX-2-dependent gene promoter region of human COX-2. The findings are supported by the results of in vivo studies, gamma mangostin could inhibit inflammation-induced edema in rats karagenen. From this research can be made resume: gamma mangostin directly inhibit the enzyme activity Ikappa B kinase, to then prevent the COX-2 gene transcription (NFkappaB target genes), decrease the production of PGE2 in the inflammatory process. 3. Anti-oxidant Activity In Moongkarndi et al. (2004) reported that extracts of mangosteen rind potential as antioxidants. Furthermore, Weecharangsan et al. (2006) follow up on these results with the research activities of some antioxidant extracts of mangosteen rind is extract the water, 50 and 95% ethanol, and ethyl acetate. The method used is penangkatapan free radical 2,2-diphenyl-1-picrylhydrazyl. The results showed that all extracts have potential as free-radical scavengers, and water and ethanol extracts have greater potential. In connection with the antioxidant activity, the extracts were also able to demonstrate neuroprotective activity in cells NG108-15. Along with these results, Jung et al. (2006) conducted a study of antioxidant activity of all compounds contains mangosteen rind, minus mangostingon. From the results of the screening antioxidant activity of these compounds, which show potent activity are: 8-hidroksikudraxanton, gartanin, alpha-mangostin, gamma-mangostin and smeathxanton A. 4. Anticancer activity To date, cancer treatment is still unsatisfactory. Therefore, the study of cancer drug discovery are still intensively conducted. One of the medicinal plants that become the object of study is the mangosteen rind. Ho et al. (2002) managed to isolate and test compounds xanton cytotoxicity effects on liver cancer cell line. Based on these studies, a compound garsinon E showed the most potent cytotoxicity activity. Sementra it, Moongkarndi et al. (2004) reported that the methanol extract of mangosteen rind menunjukka highly potent activity in inhibiting the proliferation of breast cancer cells SKBR3, and showed apoptotic activity. On the other hand, Matsumoto et al. (2003) conducted a similar test that is anti-proliferative activity and apoptosis in human leukemia HL60 cell growth. Hasl In contrast to previous studies, alpha-mangostin showed anti-proliferative activity and apoptosis terpoten xanton among other compounds. In 2004, Matsumoto et al. The study went on to study the mechanism of apoptosis of alfamangostin. The compounds are able to activate the apoptotic enzyme caspase-3 and -9, but not in caspase-8. Alpha mangostin allegedly mem-mediated mitochondrial apoptosis pathway, is based on the change in the mitochondria after treatment of these compounds for 1-2 hours. Mitochondrial changes include: swelling of cells, reduced membrane potential, decrease in intracellular ATP, the accumulation of reactive oxygen species (ROS), and the release of c / AIF cytochrome cells. However, alpha-mangostin not affect the expression of bcl-2 family proteins and activation of MAP kinase. The results of these studies indicate that the target of the action of alpha-mangostin is the mitochondria in the early phase resulting in apoptosis in human leukemia cell line. From the structure activity relationship studies, the hydroxy group has contributed greatly to the apoptotic activity. Continuing the above findings, Nabandith et al. (2004) conducted a study in vivo chemopreventive activity of alpha-mangostin in lesions preneoplastik putative involved in colon carcinogenesis rats, induced a 1.2-dimetilhidrazin (DMH). Giving these compounds for 4-5 weeks, inhibit the induction and development of aberrant crypt foci (ACF), lowering dysplastic foci (DF) and betacatenin accumulated crypts (BCAC). On the nuclear antigen labeling of cells undergoing proliferation, these compounds reduce the occurrence of focal lesions and rat colonic epithelium. 5. Activities Antimikroorganisme Besides having some pharmacological activity as above, mangosteen rind also showed activity antimikroorganisme. Suksamrarn et al. (2003) with his team from Thailand, conduct research into the potential antituberkulosa of prenylated xanton compound isolated from the skin of the mangosteen fruit. As in the previous study, alpha mangostin, gamma-mangostin and garsinon B also showed the most potent activity in this experiment. All these compounds inhibit strong against Mycobacterium tuberculosis. The findings are followed up by researchers from Osaka, Japan, Sakagami et al. (2005). Focus on alpha-mangostin, this time the compound was isolated from the bark of the tree to obtain a large amount. Alfa mangostin active against enterococci and Staphylococcus aureus bacteria were respectively resistant and methicillin vancomisin. This was reinforced by the activity of synergism with some antibiotics (gentamicin and vancomisin) against both bacteria. Meanwhile, Mahabusarakam et al. (2006) conducted a test group xanton including mangostin, in Plasmodium falciparum. The results showed that mangostin has the effect antiplasmodial middle level, while xanton prenylated which has extremely potent inhibiting alkylamino group. 6. Other activities have already mentioned that alpha-mangostin has antioxidant activity and free radical scavengers. In connection with these facts, alpha-mangostin could inhibit the oxidation of low density lipoprotein (LDL), which was instrumental in atherosclerosis (William et al., 1995). While Mahabusarakam et al. (2000) reported that xanton prenylated can also inhibit the oxidation of LDL. Research lainnnya, mangostin reported to inhibit the potent against HIV-1 protease (Chen et al., 1996). Meanwhile, Gopalakrishnan et al. (1997) reported that the compound xanton mangostin from mangosteen fruit kuliat capable of inhibiting the growth of pathogenic fungi: Fusarium oxysporum vasinfectum, Alternaria tenuis, and Dreschlera oryzae. CHAPTER IV CLOSING A. Conclusion Based on the above presentation, it can be concluded that: 1. The mangosteen (Garcinia mangostana L.) is one of the plants used as traditional medicine. The skin of the mangosteen fruit is used to treat ulcers, dysentery, sore muscles and constipation. 2. Extraction of the withdrawal activity of chemical compounds that can dissolve so that apart from the insoluble material with a liquid solvent. By knowing the active compounds contained in crude drugs would facilitate the choice of solvent and extraction right (DITJEN POM, 2000). 3. The pharmacological activity contained in extracts of mangosteen rind including anti-inflammatory, antihistamine, treatment of heart disease, antibacterial, antifungal even for the treatment or therapy of HIV disease. The most active compounds in the skin of the mangosteen fruit is alpha-mangostin, gammamangostin and garsinon-EB Suggestion that I can say is: 1. Further studies should be conducted to examine the pharmacological effects of extracts of mangosteen rind with increasing concentration. 2. We recommend testing the toxicity of extract of mangosteen rind. REFERENCES Dungir, Stevi G., et al., 2012, Phenolic Antioxidant Activity of Skin Extract Mangosteen (Garcinia mangostana L.), the journal of Science Unsrat Online, volume 1, number 1, Department of Chemistry, Science Faculty, Unsrat, Manado. Indharini, Ulfah, 2010, Determination of Levels of Α-Mangostin In infuse Dry Skin Mangosteen (Garcinia Mangostana L.), thesis. Faculty of Pharmacy, University of Muhammadiyah Surakarta, Surakarta. Manurung, Sondra, et al., 2012, the Securities Antihiperglikemia of Extract Skin Mangosteen (Garcinia mangostana l.) Against Rats Male Strain Wistar (Rattus norvegicus l.) Induced by Sucrose, research, Laboratory of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Sam Ratulangi, Manado. Nugroho. Great. Endro. 2009. Mangosteen (Garcinia mangostana L.): Skin Fruit Of The Wasted Up Being A Drug Candidates. Laboratory of Pharmacology and Toxicology, Section of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Gadjah Mada. Jogjakarta. Pasaribu, Hidayani, et al., 2012, Ethanol Extracts Test Skin Mangosteen (Garcinia mangostana L.) Against Decrease Blood Glucose. Journal of Pharmaceutics and Pharmacology, Volume 1, Number 1, Faculty of Pharmacy, University of North Sumatra, North Sumatra. Xanton is a compound composed of a tricyclic aromatic rings substituted with an assortment of phenolic groups, methoxy, and isoprene (Walker, 2007). Bark, fruit, and dried latex contains a number of Garcinia mangostana L. yellow dye derived from two metabolites that mangostin and β-mangostin (Sudarsono et al., 2002). Xanton other derivative compound is 9-hydroxycalabaxanthone, 3-isomangostin, gartanin, 8- desoxygartanin (Walker, 2007), γ-mangostin and methoxy-β- mangostin (Akao et al., 2008). The compound α-mangostin the compound is mostly found in the skin of the mangosteen fruit (Jung et al., 2006). Xanton chemical structure and its derivatives (Walker, 2007) 5. Benefits Plant According to Sudarsono et al., (2002) the mangosteen fruit is used to treat diarrhea, inflammation of the tonsils, vaginal discharge, dysentery, hemorrhoids, ulcers and toothache. Skin of the fruit is used to treat ulcers, dysentery, sore muscles, constipation. Methanol extract of mangosteen rind has the effect antiploriferatif and potent antioxidants (Moongkarndi et al, 2004). Xanton compounds contained in the skin of the mangosteen fruit can inhibit the growth of breast cancer cells, epidermoid carcinoma, small cell lung cancer and hepatocellular carcinoma (Obolskiy et al., 2009). Xanton compounds in the skin of the mangosteen fruit can inhibit the growth of colon cancer cells DLD-1 with IC50 values methoxy-β-mangostin & lt; β-mangostin & lt; α-mangostin & lt; γ-mangostin (Akao et al, 2008). The study by Matsumoto et al (2003) suggest that α-mangostin contained in mangosteen rind has a 6 antiploriferatif activity against HL60 leukemia cells by inducing apoptosis. According to research Jung et al. (2006), α-mangostin has antibacterial activity against Mycobacterium tuberculosis with IC50 values of 6.25 ug / ml, and have antioxidant activity with IC50 value of 1.0 ug / ml. B. The compound α-α-mangostin mangostin compound is the compound is mostly found in the skin of the mangosteen fruit (Figure 2). The compound α-mangostin an amorphous yellow crystals which have a melting point 180-182oC. Uptake was high in the UV region at wavelengths of 215, 243 and 317 nm (Ee et al., 2005). The compound α-mangostin tend to be non-polar, so it will be easily dissolved in solvents which are non polar, such as hexane (Walker, 2007). The chemical structure of α-mangostin (Walker, 2007) Assay of α-mangostin can be done using TLC and HPLC. Methods TLC using chloroform mobile phase: ethyl acetate: methanol (80: 10: 5), with a stationary phase silica gel 60F245, UV detection at 366 nm and obtained α-mangostin HRF price amounting to 50.0 (Pothitirat and Gritsanapan, 2008). HPLC method using a mobile phase of 0.1% phosphoric acid: acetonitrile with C18 stationary phase (Pothitirat and Gritsanapan, 2009). Research that has been conducted Walker (2007) by the HPLC method using a mobile phase of methanol: 0.1% formic acid in water (75:25) can separate compounds xanton compound found in mangosteen. C. Forms of preparations Herbal preparations are preparations herbal traditional medicine made in a simple manner such as infusion, decoction, and in part derived from botanicals. Simplicia is a natural substance in the form of a whole plant, plant part or exudates of plants used as medicine, and has not undergone processing in a simple and yet a pure substance unless otherwise stated, in the form of material that has dried (MOH, 2000). The dosage forms of medicinal plants that have long been used, among others: 1. infuse infusion is a liquid preparation made with quote simplisia vegetable with water at a temperature of 90 ° C for 15 minutes (MOH RI, 1979). Infundation is penyarian process that is generally used to sum up the content of the active substance is soluble in water than plant-based ingredients (MOH, 1986). Making infuse the simplest way to make a herbal preparation of soft material such as leaves and flowers (MOH RI, 2000). 2. decoction decoction is a liquid preparation made by extracting herbal preparations with water at a temperature of 90 ° C for 30 minutes (MOH RI, 2000). 3. Making preparations tea tea for medicinal purposes as much done based on the experience in the manufacture of infusion were performed on black tea as a beverage (MOH RI, 2000). Some things need to be considered in the preparation of tea are: the number of bulbs and water, and the degree of fineness simplisia. Total crude drug dose expressed in grams and water in ml dose. While the degree of gloss to the wood, bark and roots chopped a bit rough with a size of approximately 2.5 mm (MOH RI, 2000). CHAPTER III DISCUSSION A. Definition Mangosteen Fruit Mangosteen (Garcinia mangostana L.) is a plant originating from the region of Southeast Asia including Indonesia, Malaysia, Thailand and Myanmar. Mangosteen is a functional plants because most of these plants can be used as a drug. However, many do not know if the mangosteen rind has efficacy. The skin of the mangosteen fruit that had been discarded as waste after it is eating the meat of fruit, it has a myriad of important benefits for health. In the skin of the mangosteen fruit is rich in antioxidants such as xanthones and anthocyanins (Moongkandi, et al., 2004; Kristenses, 2005; Weecharangsan, et al., 2006; Hartanto 2011). The mangosteen fruit is round and dark purple color because it contains a lot of anthocyanins in the skin (Obolskiy et al., 2009). In the fruit pulp are 5-6. Have 1-3 seeds, seed membrane thick juicy, white and edible. Mangosteen tree has a root fibers. On the following pages viewable image of the mangosteen fruit crops. The skin of the mangosteen fruit contains compounds that have pharmacological activity as anti-inflammatory, antihistamine, antibacterial, antifungal, cancer, hypertension, stroke and HIV therapy. Some of the main compounds of the content of mangosteen rind has a class of pharmacological activity xanton (Nugroho, 2009). Besides According Polytechnic full education website competition (2010), mangosteen rind is also used to treat ulcers, dysentery, sore muscles, constipation, and even Anti-fatigue (energize), Anti-oxidant (removing toxins from the body), Anti-seborrheaic (menpercantik skin), Anti-obesity (to lose weight), Anti-glaucomic (sore eye / glaucoma). B. Methods of Extraction The extraction process is done by stopping the enzyme activity in plant tissue beforehand to prevent oxidation or hydrolysis enzyme (Harborne, 1987). Extraction activity in the form of withdrawal of chemical compounds that can dissolve so that apart from the insoluble material with a liquid solvent. By knowing the active compounds contained in crude drugs would facilitate the choice of solvent and extraction right (DITJEN POM, 2000). Making extract in this study using maceration method. Maceration can be done by including 10 parts simplisia with degrees delicate that fit into the vessel, covered with 75 parts liquid penyari, closed, left for 5 days protected from light while stirring often, serkai, wring it out, wash the pulp with liquid penyari sufficient to obtain 100 part. Move into the closed vessel, leave in a cool place, protected from light, for 2 days. Enap pour or strain (Pharmacopoeia, 1979). C. Pharmacological Activities And Antioxidants Utilization mangosteen rind has actually been done long ago. The skin of the mangosteen fruit is traditionally used on a variety of treatment in the State of India, Sri rare Myanmar, and Thailand (Mahabusarakam et al., 1987). Broadly, the Thai people take advantage of mangosteen rind for the treatment of canker sores, dysentery, cystitis, diarrhea, gonorrhea, and eczema (ICUC, 2003). In the modern era, the use of mangosteen kuliat widely in the country sparked the interest of scientists for investigating and developing lembih keberkhasiatan further scientific aspects of the mangosteen rind. Many studies have proven the efficacy of mangosteen rind, and are even finding compounds that are responsible for these effects. The following will be presented a discussion of the pharmacological effects of mangosteen rind. 1. Activities antihistamine in allergic reactions, the main component of which took Beran important mast cells, and their mediators, namely the release of histamine and serotonin. Allergies are caused by the immune response to an antigen or allergen interacts with B lymphocytes to produce immunoglobulin E (IgE). Imunoglubulin E produced then attaches itself to the receptor FcεRI on the surface of mast cell membrane. Upon their return interaction between antigen-antibody, will stimulate mast cells to release histamine (Kresno, 2001; Subowo, 1993). Associated with allergic reactions or the release of histamine, Chairungsrilerd et al. (1996a, 1996b, 1998) to test the methanol extract of mangosteen rind to the contraction of isolated rabbit aorta chest induced by histamine and serotonin. From the analysis of the active components of the result of the continued fraction silica gel chromatography, indicating that the active compound is alpha and gamma mangostin. Alpha mangostin itself able to demonstrate the inhibitory activity contracted guinea pig isolated trachea and aorta piston isolated rabbit, induced cimetidine, histamine H2 receptor antagonists. However, these compounds do not show activity on the contraction induced karbakol, phenylephrine and KCl. Alpha mangostin was also able to inhibit binding of [3H] mepyramine against arta smooth muscle cells of rats. The latter compound is a specific antagonist for histamine H1 receptor. From the analysis of the kinetics of binding of [3H] mepyramine megnindikasikan that competitively inhibit alpha mangostin. This study suggests that alpha-mangostin is categorized as any blocks H1 receptors histaminergik particular, while gamma mangostin as any blocks serotonergic receptors, especially the 5-hydroxytryptamine 2A or 5HT2A. Furthermore, Nakatani et al. (2002a) conducted research into the mechanism toward the mangosteen rind extract. In the study of mangosteen peel extract is: 100% ethanol, 70%, 40%, and water, tested against prostaglandin E2 synthesis and release of histamine. 40% ethanol extract showed the most potent effect in inhibiting histamine release from RBL 2H3- cell-mediated IgE. All mangosteen rind extract capable of inhibiting the synthesis of PGE2 from rat glioma cells induced Ca2 + ionophore A23187. In the passive cutaneous anaphylaxis reaction, all of mangosteen peel extract also shows the inhibitory activity of the reaction. From this study, 40% ethanol extract of mangosteen is the most potent in inhibiting PGE2 synthesis and release of histamine. 2. Anti-inflammatory Activity Research on anti-inflammatory activity of mangosteen rind until now only performed on the stages of in vitro and in vivo to a new stage in the study with rats induced karagenen method. From the research results suggested that compounds that have anti-inflammatory activity is gamma-mangostin. Gamma-mangostin is xanton diprenilasi tetraoksigenasi form, the chemical structure can be seen in Fig. Nakatni et al. (2002b) conducted a study of anti-inflammatory activity in vitro of gamma mangostin against PGE2 synthesis and cyclooxygenase (COX) in rat C6 glioma cells. Both the compound and the enzyme is an important mediator in the inflammatory reaction. Gamma-mangostin potently inhibit the release of PGE2 in rat C6 glioma cells induced Ca2 + ionophore A23187. Gammamangostin inhibit the conversion of arachidonic acid to PGE2 in the microsomal, there is a possibility of cyclooxygenase inhibition on track. In experiments in vitro enzymatic, this compound is able to inhibit the activity of the enzyme COX-1 and COX-2. However, these compounds have no significant effect on: (1) phosphorylation signal ekstraseuler p42 / p44 induced A23187, which regulates activated protein kinase kinase / mitogen, and (2) release of [14C] arachidonic -asam of cells labeled [14C ] the Aa. From this study, gamma mangostin has anti-inflammatory activity by inhibiting the activity of cyclooxygenase (COX). Furthermore, Nakatani et al. (2004) analyzed the effect of gamma-mangostin against COX-2 gene expression in rat C6 glioma cells. Gamma mangostin inhibits protein and mRNA expression of COX-2 induced by lipopolysaccharide, but no effect on protein expression of COX-1. Lipopolysaccharide serves to stimulate phosphorylation inhibitor kappaB (IkappaB) mediated IkappaB kinase, which then further degradation and induces nuclear translocation of NF-kappaB ligand that activates gene transcription of COX-2. In connection with that, it also inhibits gamma mangostin IkappaB kinase activity and decreases degradation IkappaB and LPS-induced phosphorylation. In luciferase reporter assay, the compound lowering the NF-kappaB activation induced by LPS and the process of gene transcription of COX-2-dependent gene promoter region of human COX-2. The findings are supported by the results of in vivo studies, gamma mangostin could inhibit inflammation-induced edema in rats karagenen. From this research can be made resume: gamma mangostin directly inhibit the enzyme activity Ikappa B kinase, to then prevent the COX-2 gene transcription (NFkappaB target genes), decrease the production of PGE2 in the inflammatory process. 3. Anti-oxidant Activity In Moongkarndi et al. (2004) reported that extracts of mangosteen rind potential as antioxidants. Furthermore, Weecharangsan et al. (2006) follow up on these results with the research activities of some antioxidant extracts of mangosteen rind is extract the water, 50 and 95% ethanol, and ethyl acetate. The method used is penangkatapan free radical 2,2-diphenyl-1-picrylhydrazyl. The results showed that all extracts have potential as free-radical scavengers, and water and ethanol extracts have greater potential. In connection with the antioxidant activity, the extracts were also able to demonstrate neuroprotective activity in cells NG108-15. Along with these results, Jung et al. (2006) conducted a study of antioxidant activity of all compounds contains mangosteen rind, minus mangostingon. From the results of the screening antioxidant activity of these compounds, which show potent activity are: 8-hidroksikudraxanton, gartanin, alpha-mangostin, gamma-mangostin and smeathxanton A. 4. Anticancer activity To date, cancer treatment is still unsatisfactory. Therefore, the study of cancer drug discovery are still intensively conducted. One of the medicinal plants that become the object of study is the mangosteen rind. Ho et al. (2002) managed to isolate and test compounds xanton cytotoxicity effects on liver cancer cell line. Based on these studies, a compound garsinon E showed the most potent cytotoxicity activity. Sementra it, Moongkarndi et al. (2004) reported that the methanol extract of mangosteen rind menunjukka highly potent activity in inhibiting the proliferation of breast cancer cells SKBR3, and showed apoptotic activity. On the other hand, Matsumoto et al. (2003) conducted a similar test that is anti-proliferative activity and apoptosis in human leukemia HL60 cell growth. Hasl In contrast to previous studies, alpha-mangostin showed anti-proliferative activity and apoptosis terpoten xanton among other compounds. In 2004, Matsumoto et al. The study went on to study the mechanism of apoptosis of alfamangostin. The compounds are able to activate the apoptotic enzyme caspase-3 and -9, but not in caspase-8. Alpha mangostin allegedly mem-mediated mitochondrial apoptosis pathway, is based on the change in the mitochondria after treatment of these compounds for 1-2 hours. Mitochondrial changes include: swelling of cells, reduced membrane potential, decrease in intracellular ATP, the accumulation of reactive oxygen species (ROS), and the release of c / AIF cytochrome cells. However, alpha-mangostin not affect the expression of bcl-2 family proteins and activation of MAP kinase. The results of these studies indicate that the target of the action of alpha-mangostin is the mitochondria in the early phase resulting in apoptosis in human leukemia cell line. From the structure activity relationship studies, the hydroxy group has contributed greatly to the apoptotic activity. Continuing the above findings, Nabandith et al. (2004) conducted a study in vivo chemopreventive activity of alpha-mangostin in lesions preneoplastik putative involved in colon carcinogenesis rats, induced a 1.2-dimetilhidrazin (DMH). Giving these compounds for 4-5 weeks, inhibit the induction and development of aberrant crypt foci (ACF), lowering dysplastic foci (DF) and betacatenin accumulated crypts (BCAC). On the nuclear antigen labeling of cells undergoing proliferation, these compounds reduce the occurrence of focal lesions and rat colonic epithelium. 5. Activities Antimikroorganisme Besides having some pharmacological activity as above, mangosteen rind also showed activity antimikroorganisme. Suksamrarn et al. (2003) with his team from Thailand, conduct research into the potential antituberkulosa of prenylated xanton compound isolated from the skin of the mangosteen fruit. As in the previous study, alpha mangostin, gamma-mangostin and garsinon B also showed the most potent activity in this experiment. All these compounds inhibit strong against Mycobacterium tuberculosis. The findings are followed up by researchers from Osaka, Japan, Sakagami et al. (2005). Focus on alpha-mangostin, this time the compound was isolated from the bark of the tree to obtain a large amount. Alfa mangostin active against enterococci and Staphylococcus aureus bacteria were respectively resistant and methicillin vancomisin. This was reinforced by the activity of synergism with some antibiotics (gentamicin and vancomisin) against both bacteria. Meanwhile, Mahabusarakam et al. (2006) conducted a test group xanton including mangostin, in Plasmodium falciparum. The results showed that mangostin has the effect antiplasmodial middle level, while xanton prenylated which has extremely potent inhibiting alkylamino group. 6. Other activities have already mentioned that alpha-mangostin has antioxidant activity and free radical scavengers. In connection with these facts, alpha-mangostin could inhibit the oxidation of low density lipoprotein (LDL), which was instrumental in atherosclerosis (William et al., 1995). While Mahabusarakam et al. (2000) reported that xanton prenylated can also inhibit the oxidation of LDL. Research lainnnya, mangostin reported to inhibit the potent against HIV-1 protease (Chen et al., 1996). Meanwhile, Gopalakrishnan et al. (1997) reported that the compound xanton mangostin from mangosteen fruit kuliat capable of inhibiting the growth of pathogenic fungi: Fusarium oxysporum vasinfectum, Alternaria tenuis, and Dreschlera oryzae. CHAPTER IV CLOSING A. Conclusion Based on the above presentation, it can be concluded that: 1. The mangosteen (Garcinia mangostana L.) is one of the plants used as traditional medicine. The skin of the mangosteen fruit is used to treat ulcers, dysentery, sore muscles and constipation. 2. Extraction of the withdrawal activity of chemical compounds that can dissolve so that apart from the insoluble material with a liquid solvent. By knowing the active compounds contained in crude drugs would facilitate the choice of solvent and extraction right (DITJEN POM, 2000). 3. The pharmacological activity contained in extracts of mangosteen rind including anti-inflammatory, antihistamine, treatment of heart disease, antibacterial, antifungal even for the treatment or therapy of HIV disease. The most active compounds in the skin of the mangosteen fruit is alpha-mangostin, gammamangostin and garsinon-EB Suggestion that I can say is: 1. Further studies should be conducted to examine the pharmacological effects of extracts of mangosteen rind with increasing concentration. 2. We recommend testing the toxicity of extract of mangosteen rind. REFERENCES Dungir, Stevi G., et al., 2012, Phenolic Antioxidant Activity of Skin Extract Mangosteen (Garcinia mangostana L.), the journal of Science Unsrat Online, volume 1, number 1, Department of Chemistry, Science Faculty, Unsrat, Manado. Indharini, Ulfah, 2010, Determination of Levels of Α-Mangostin In infuse Dry Skin Mangosteen (Garcinia Mangostana L.), thesis. Faculty of Pharmacy, University of Muhammadiyah Surakarta, Surakarta. Manurung, Sondra, et al., 2012, the Securities Antihiperglikemia of Extract Skin Mangosteen (Garcinia mangostana l.) Against Rats Male Strain Wistar (Rattus norvegicus l.) Induced by Sucrose, research, Laboratory of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Sam Ratulangi, Manado. Nugroho. Great. Endro. 2009. Mangosteen (Garcinia mangostana L.): Skin Fruit Of The Wasted Up Being A Drug Candidates. Laboratory of Pharmacology and Toxicology, Section of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Gadjah Mada. Jogjakarta. Pasaribu, Hidayani, et al., 2012, Ethanol Extracts Test Skin Mangosteen (Garcinia mangostana L.) Against Decrease Blood Glucose. Journal of Pharmaceutics and Pharmacology, Volume 1, Number 1, Faculty of Pharmacy, University of North Sumatra, North Sumatra. Xanton is a compound composed of a tricyclic aromatic rings substituted with an assortment of phenolic groups, methoxy, and isoprene (Walker, 2007). Bark, fruit, and dried latex contains a number of Garcinia mangostana L. yellow dye derived from two metabolites that mangostin and β-mangostin (Sudarsono et al., 2002). Xanton other derivative compound is 9-hydroxycalabaxanthone, 3-isomangostin, gartanin, 8- desoxygartanin (Walker, 2007), γ-mangostin and methoxy-β- mangostin (Akao et al., 2008). The compound α-mangostin the compound is mostly found in the skin of the mangosteen fruit (Jung et al., 2006). Xanton chemical structure and its derivatives (Walker, 2007) 5. Benefits Plant According to Sudarsono et al., (2002) the mangosteen fruit is used to treat diarrhea, inflammation of the tonsils, vaginal discharge, dysentery, hemorrhoids, ulcers and toothache. Skin of the fruit is used to treat ulcers, dysentery, sore muscles, constipation. Methanol extract of mangosteen rind has the effect antiploriferatif and potent antioxidants (Moongkarndi et al, 2004). Xanton compounds contained in the skin of the mangosteen fruit can inhibit the growth of breast cancer cells, epidermoid carcinoma, small cell lung cancer and hepatocellular carcinoma (Obolskiy et al., 2009). Xanton compounds in the skin of the mangosteen fruit can inhibit the growth of colon cancer cells DLD-1 with IC50 values methoxy-β-mangostin & lt; β-mangostin & lt; α-mangostin & lt; γ-mangostin (Akao et al, 2008). The study by Matsumoto et al (2003) suggest that α-mangostin contained in mangosteen rind has a 6 antiploriferatif activity against HL60 leukemia cells by inducing apoptosis. According to research Jung et al. (2006), α-mangostin has antibacterial activity against Mycobacterium tuberculosis with IC50 values of 6.25 ug / ml, and have antioxidant activity with IC50 value of 1.0 ug / ml. B. The compound α-α-mangostin mangostin compound is the compound is mostly found in the skin of the mangosteen fruit (Figure 2). The compound α-mangostin an amorphous yellow crystals which have a melting point 180-182oC. Uptake was high in the UV region at wavelengths of 215, 243 and 317 nm (Ee et al., 2005). The compound α-mangostin tend to be non-polar, so it will be easily dissolved in solvents which are non polar, such as hexane (Walker, 2007). The chemical structure of α-mangostin (Walker, 2007) Assay of α-mangostin can be done using TLC and HPLC. Methods TLC using chloroform mobile phase: ethyl acetate: methanol (80: 10: 5), with a stationary phase silica gel 60F245, UV detection at 366 nm and obtained α-mangostin HRF price amounting to 50.0 (Pothitirat and Gritsanapan, 2008). HPLC method using a mobile phase of 0.1% phosphoric acid: acetonitrile with C18 stationary phase (Pothitirat and Gritsanapan, 2009). Research that has been conducted Walker (2007) by the HPLC method using a mobile phase of methanol: 0.1% formic acid in water (75:25) can separate compounds xanton compound found in mangosteen. C. Forms of preparations Herbal preparations are preparations herbal traditional medicine made in a simple manner such as infusion, decoction, and in part derived from botanicals. Simplicia is a natural substance in the form of a whole plant, plant part or exudates of plants used as medicine, and has not undergone processing in a simple and yet a pure substance unless otherwise stated, in the form of material that has dried (MOH, 2000). The dosage forms of medicinal plants that have long been used, among others: 1. infuse infusion is a liquid preparation made with quote simplisia vegetable with water at a temperature of 90 ° C for 15 minutes (MOH RI, 1979). Infundation is penyarian process that is generally used to sum up the content of the active substance is soluble in water than plant-based ingredients (MOH, 1986). Making infuse the simplest way to make a herbal preparation of soft material such as leaves and flowers (MOH RI, 2000). 2. decoction decoction is a liquid preparation made by extracting herbal preparations with water at a temperature of 90 ° C for 30 minutes (MOH RI, 2000). 3. Making preparations tea tea for medicinal purposes as much done based on the experience in the manufacture of infusion were performed on black tea as a beverage (MOH RI, 2000). Some things need to be considered in the preparation of tea are: the number of bulbs and water, and the degree of fineness simplisia. Total crude drug dose expressed in grams and water in ml dose. While the degree of gloss to the wood, bark and roots chopped a bit rough with a size of approximately 2.5 mm (MOH RI, 2000). CHAPTER III DISCUSSION A. Definition Mangosteen Fruit Mangosteen (Garcinia mangostana L.) is a plant originating from the region of Southeast Asia including Indonesia, Malaysia, Thailand and Myanmar. Mangosteen is a functional plants because most of these plants can be used as a drug. However, many do not know if the mangosteen rind has efficacy. The skin of the mangosteen fruit that had been discarded as waste after it is eating the meat of fruit, it has a myriad of important benefits for health. In the skin of the mangosteen fruit is rich in antioxidants such as xanthones and anthocyanins (Moongkandi, et al., 2004; Kristenses, 2005; Weecharangsan, et al., 2006; Hartanto 2011). The mangosteen fruit is round and dark purple color because it contains a lot of anthocyanins in the skin (Obolskiy et al., 2009). In the fruit pulp are 5-6. Have 1-3 seeds, seed membrane thick juicy, white and edible. Mangosteen tree has a root fibers. On the following pages viewable image of the mangosteen fruit crops. The skin of the mangosteen fruit contains compounds that have pharmacological activity as anti-inflammatory, antihistamine, antibacterial, antifungal, cancer, hypertension, stroke and HIV therapy. Some of the main compounds of the content of mangosteen rind has a class of pharmacological activity xanton (Nugroho, 2009). Besides According Polytechnic full education website competition (2010), mangosteen rind is also used to treat ulcers, dysentery, sore muscles, constipation, and even Anti-fatigue (energize), Anti-oxidant (removing toxins from the body), Anti-seborrheaic (menpercantik skin), Anti-obesity (to lose weight), Anti-glaucomic (sore eye / glaucoma). B. Methods of Extraction The extraction process is done by stopping the enzyme activity in plant tissue beforehand to prevent oxidation or hydrolysis enzyme (Harborne, 1987). Extraction activity in the form of withdrawal of chemical compounds that can dissolve so that apart from the insoluble material with a liquid solvent. By knowing the active compounds contained in crude drugs would facilitate the choice of solvent and extraction right (DITJEN POM, 2000). Making extract in this study using maceration method. Maceration can be done by including 10 parts simplisia with degrees delicate that fit into the vessel, covered with 75 parts liquid penyari, closed, left for 5 days protected from light while stirring often, serkai, wring it out, wash the pulp with liquid penyari sufficient to obtain 100 part. Move into the closed vessel, leave in a cool place, protected from light, for 2 days. Enap pour or strain (Pharmacopoeia, 1979). C. Pharmacological Activities And Antioxidants Utilization mangosteen rind has actually been done long ago. The skin of the mangosteen fruit is traditionally used on a variety of treatment in the State of India, Sri rare Myanmar, and Thailand (Mahabusarakam et al., 1987). Broadly, the Thai people take advantage of mangosteen rind for the treatment of canker sores, dysentery, cystitis, diarrhea, gonorrhea, and eczema (ICUC, 2003). In the modern era, the use of mangosteen kuliat widely in the country sparked the interest of scientists for investigating and developing lembih keberkhasiatan further scientific aspects of the mangosteen rind. Many studies have proven the efficacy of mangosteen rind, and are even finding compounds that are responsible for these effects. The following will be presented a discussion of the pharmacological effects of mangosteen rind. 1. Activities antihistamine in allergic reactions, the main component of which took Beran important mast cells, and their mediators, namely the release of histamine and serotonin. Allergies are caused by the immune response to an antigen or allergen interacts with B lymphocytes to produce immunoglobulin E (IgE). Imunoglubulin E produced then attaches itself to the receptor FcεRI on the surface of mast cell membrane. Upon their return interaction between antigen-antibody, will stimulate mast cells to release histamine (Kresno, 2001; Subowo, 1993). Associated with allergic reactions or the release of histamine, Chairungsrilerd et al. (1996a, 1996b, 1998) to test the methanol extract of mangosteen rind to the contraction of isolated rabbit aorta chest induced by histamine and serotonin. From the analysis of the active components of the result of the continued fraction silica gel chromatography, indicating that the active compound is alpha and gamma mangostin. Alpha mangostin itself able to demonstrate the inhibitory activity contracted guinea pig isolated trachea and aorta piston isolated rabbit, induced cimetidine, histamine H2 receptor antagonists. However, these compounds do not show activity on the contraction induced karbakol, phenylephrine and KCl. Alpha mangostin was also able to inhibit binding of [3H] mepyramine against arta smooth muscle cells of rats. The latter compound is a specific antagonist for histamine H1 receptor. From the analysis of the kinetics of binding of [3H] mepyramine megnindikasikan that competitively inhibit alpha mangostin. This study suggests that alpha-mangostin is categorized as any blocks H1 receptors histaminergik particular, while gamma mangostin as any blocks serotonergic receptors, especially the 5-hydroxytryptamine 2A or 5HT2A. Furthermore, Nakatani et al. (2002a) conducted research into the mechanism toward the mangosteen rind extract. In the study of mangosteen peel extract is: 100% ethanol, 70%, 40%, and water, tested against prostaglandin E2 synthesis and release of histamine. 40% ethanol extract showed the most potent effect in inhibiting histamine release from RBL 2H3- cell-mediated IgE. All mangosteen rind extract capable of inhibiting the synthesis of PGE2 from rat glioma cells induced Ca2 + ionophore A23187. In the passive cutaneous anaphylaxis reaction, all of mangosteen peel extract also shows the inhibitory activity of the reaction. From this study, 40% ethanol extract of mangosteen is the most potent in inhibiting PGE2 synthesis and release of histamine. 2. Anti-inflammatory Activity Research on anti-inflammatory activity of mangosteen rind until now only performed on the stages of in vitro and in vivo to a new stage in the study with rats induced karagenen method. From the research results suggested that compounds that have anti-inflammatory activity is gamma-mangostin. Gamma-mangostin is xanton diprenilasi tetraoksigenasi form, the chemical structure can be seen in Fig. Nakatni et al. (2002b) conducted a study of anti-inflammatory activity in vitro of gamma mangostin against PGE2 synthesis and cyclooxygenase (COX) in rat C6 glioma cells. Both the compound and the enzyme is an important mediator in the inflammatory reaction. Gamma-mangostin potently inhibit the release of PGE2 in rat C6 glioma cells induced Ca2 + ionophore A23187. Gammamangostin inhibit the conversion of arachidonic acid to PGE2 in the microsomal, there is a possibility of cyclooxygenase inhibition on track. In experiments in vitro enzymatic, this compound is able to inhibit the activity of the enzyme COX-1 and COX-2. However, these compounds have no significant effect on: (1) phosphorylation signal ekstraseuler p42 / p44 induced A23187, which regulates activated protein kinase kinase / mitogen, and (2) release of [14C] arachidonic -asam of cells labeled [14C ] the Aa. From this study, gamma mangostin has anti-inflammatory activity by inhibiting the activity of cyclooxygenase (COX). Furthermore, Nakatani et al. (2004) analyzed the effect of gamma-mangostin against COX-2 gene expression in rat C6 glioma cells. Gamma mangostin inhibits protein and mRNA expression of COX-2 induced by lipopolysaccharide, but no effect on protein expression of COX-1. Lipopolysaccharide serves to stimulate phosphorylation inhibitor kappaB (IkappaB) mediated IkappaB kinase, which then further degradation and induces nuclear translocation of NF-kappaB ligand that activates gene transcription of COX-2. In connection with that, it also inhibits gamma mangostin IkappaB kinase activity and decreases degradation IkappaB and LPS-induced phosphorylation. In luciferase reporter assay, the compound lowering the NF-kappaB activation induced by LPS and the process of gene transcription of COX-2-dependent gene promoter region of human COX-2. The findings are supported by the results of in vivo studies, gamma mangostin could inhibit inflammation-induced edema in rats karagenen. From this research can be made resume: gamma mangostin directly inhibit the enzyme activity Ikappa B kinase, to then prevent the COX-2 gene transcription (NFkappaB target genes), decrease the production of PGE2 in the inflammatory process. 3. Anti-oxidant Activity In Moongkarndi et al. (2004) reported that extracts of mangosteen rind potential as antioxidants. Furthermore, Weecharangsan et al. (2006) follow up on these results with the research activities of some antioxidant extracts of mangosteen rind is extract the water, 50 and 95% ethanol, and ethyl acetate. The method used is penangkatapan free radical 2,2-diphenyl-1-picrylhydrazyl. The results showed that all extracts have potential as free-radical scavengers, and water and ethanol extracts have greater potential. In connection with the antioxidant activity, the extracts were also able to demonstrate neuroprotective activity in cells NG108-15. Along with these results, Jung et al. (2006) conducted a study of antioxidant activity of all compounds contains mangosteen rind, minus mangostingon. From the results of the screening antioxidant activity of these compounds, which show potent activity are: 8-hidroksikudraxanton, gartanin, alpha-mangostin, gamma-mangostin and smeathxanton A. 4. Anticancer activity To date, cancer treatment is still unsatisfactory. Therefore, the study of cancer drug discovery are still intensively conducted. One of the medicinal plants that become the object of study is the mangosteen rind. Ho et al. (2002) managed to isolate and test compounds xanton cytotoxicity effects on liver cancer cell line. Based on these studies, a compound garsinon E showed the most potent cytotoxicity activity. Sementra it, Moongkarndi et al. (2004) reported that the methanol extract of mangosteen rind menunjukka highly potent activity in inhibiting the proliferation of breast cancer cells SKBR3, and showed apoptotic activity. On the other hand, Matsumoto et al. (2003) conducted a similar test that is anti-proliferative activity and apoptosis in human leukemia HL60 cell growth. Hasl In contrast to previous studies, alpha-mangostin showed anti-proliferative activity and apoptosis terpoten xanton among other compounds. In 2004, Matsumoto et al. The study went on to study the mechanism of apoptosis of alfamangostin. The compounds are able to activate the apoptotic enzyme caspase-3 and -9, but not in caspase-8. Alpha mangostin allegedly mem-mediated mitochondrial apoptosis pathway, is based on the change in the mitochondria after treatment of these compounds for 1-2 hours. Mitochondrial changes include: swelling of cells, reduced membrane potential, decrease in intracellular ATP, the accumulation of reactive oxygen species (ROS), and the release of c / AIF cytochrome cells. However, alpha-mangostin not affect the expression of bcl-2 family proteins and activation of MAP kinase. The results of these studies indicate that the target of the action of alpha-mangostin is the mitochondria in the early phase resulting in apoptosis in human leukemia cell line. From the structure activity relationship studies, the hydroxy group has contributed greatly to the apoptotic activity. Continuing the above findings, Nabandith et al. (2004) conducted a study in vivo chemopreventive activity of alpha-mangostin in lesions preneoplastik putative involved in colon carcinogenesis rats, induced a 1.2-dimetilhidrazin (DMH). Giving these compounds for 4-5 weeks, inhibit the induction and development of aberrant crypt foci (ACF), lowering dysplastic foci (DF) and betacatenin accumulated crypts (BCAC). On the nuclear antigen labeling of cells undergoing proliferation, these compounds reduce the occurrence of focal lesions and rat colonic epithelium. 5. Activities Antimikroorganisme Besides having some pharmacological activity as above, mangosteen rind also showed activity antimikroorganisme. Suksamrarn et al. (2003) with his team from Thailand, conduct research into the potential antituberkulosa of prenylated xanton compound isolated from the skin of the mangosteen fruit. As in the previous study, alpha mangostin, gamma-mangostin and garsinon B also showed the most potent activity in this experiment. All these compounds inhibit strong against Mycobacterium tuberculosis. The findings are followed up by researchers from Osaka, Japan, Sakagami et al. (2005). Focus on alpha-mangostin, this time the compound was isolated from the bark of the tree to obtain a large amount. Alfa mangostin active against enterococci and Staphylococcus aureus bacteria were respectively resistant and methicillin vancomisin. This was reinforced by the activity of synergism with some antibiotics (gentamicin and vancomisin) against both bacteria. Meanwhile, Mahabusarakam et al. (2006) conducted a test group xanton including mangostin, in Plasmodium falciparum. The results showed that mangostin has the effect antiplasmodial middle level, while xanton prenylated which has extremely potent inhibiting alkylamino group. 6. Other activities have already mentioned that alpha-mangostin has antioxidant activity and free radical scavengers. In connection with these facts, alpha-mangostin could inhibit the oxidation of low density lipoprotein (LDL), which was instrumental in atherosclerosis (William et al., 1995). While Mahabusarakam et al. (2000) reported that xanton prenylated can also inhibit the oxidation of LDL. Research lainnnya, mangostin reported to inhibit the potent against HIV-1 protease (Chen et al., 1996). Meanwhile, Gopalakrishnan et al. (1997) reported that the compound xanton mangostin from mangosteen fruit kuliat capable of inhibiting the growth of pathogenic fungi: Fusarium oxysporum vasinfectum, Alternaria tenuis, and Dreschlera oryzae. CHAPTER IV CLOSING A. Conclusion Based on the above presentation, it can be concluded that: 1. The mangosteen (Garcinia mangostana L.) is one of the plants used as traditional medicine. The skin of the mangosteen fruit is used to treat ulcers, dysentery, sore muscles and constipation. 2. Extraction of the withdrawal activity of chemical compounds that can dissolve so that apart from the insoluble material with a liquid solvent. By knowing the active compounds contained in crude drugs would facilitate the choice of solvent and extraction right (DITJEN POM, 2000). 3. The pharmacological activity contained in extracts of mangosteen rind including anti-inflammatory, antihistamine, treatment of heart disease, antibacterial, antifungal even for the treatment or therapy of HIV disease. The most active compounds in the skin of the mangosteen fruit is alpha-mangostin, gammamangostin and garsinon-EB Suggestion that I can say is: 1. Further studies should be conducted to examine the pharmacological effects of extracts of mangosteen rind with increasing concentration. 2. We recommend testing the toxicity of extract of mangosteen rind. REFERENCES Dungir, Stevi G., et al., 2012, Phenolic Antioxidant Activity of Skin Extract Mangosteen (Garcinia mangostana L.), the journal of Science Unsrat Online, volume 1, number 1, Department of Chemistry, Science Faculty, Unsrat, Manado. Indharini, Ulfah, 2010, Determination of Levels of Α-Mangostin In infuse Dry Skin Mangosteen (Garcinia Mangostana L.), thesis. Faculty of Pharmacy, University of Muhammadiyah Surakarta, Surakarta. Manurung, Sondra, et al., 2012, the Securities Antihiperglikemia of Extract Skin Mangosteen (Garcinia mangostana l.) Against Rats Male Strain Wistar (Rattus norvegicus l.) Induced by Sucrose, research, Laboratory of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Sam Ratulangi, Manado. Nugroho. Great. Endro. 2009. Mangosteen (Garcinia mangostana L.): Skin Fruit Of The Wasted Up Being A Drug Candidates. Laboratory of Pharmacology and Toxicology, Section of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Gadjah Mada. Jogjakarta. Pasaribu, Hidayani, et al., 2012, Ethanol Extracts Test Skin Mangosteen (Garcinia mangostana L.) Against Decrease Blood Glucose. Journal of Pharmaceutics and Pharmacology, Volume 1, Number 1, Faculty of Pharmacy, University of North Sumatra, North Sumatra. will stimulate mast cells to release histamine (Kresno, 2001; Subowo, 1993). Associated with allergic reactions or the release of histamine, Chairungsrilerd et al. (1996a, 1996b, 1998) to test the methanol extract of mangosteen rind to the contraction of isolated rabbit aorta chest induced by histamine and serotonin. From the analysis of the active components of the result of the continued fraction silica gel chromatography, indicating that the active compound is alpha and gamma mangostin. Alpha mangostin itself able to demonstrate the inhibitory activity contracted guinea pig isolated trachea and aorta piston isolated rabbit, induced cimetidine, histamine H2 receptor antagonists. However, these compounds do not show activity on the contraction induced karbakol, phenylephrine and KCl. Alpha mangostin was also able to inhibit binding of [3H] mepyramine against arta smooth muscle cells of rats. The latter compound is a specific antagonist for histamine H1 receptor. From the analysis of the kinetics of binding of [3H] mepyramine megnindikasikan that competitively inhibit alpha mangostin. This study suggests that alpha-mangostin is categorized as any blocks H1 receptors histaminergik particular, while gamma mangostin as any blocks serotonergic receptors, especially the 5-hydroxytryptamine 2A or 5HT2A. Furthermore, Nakatani et al. (2002a) conducted research into the mechanism toward the mangosteen rind extract. In the study of mangosteen peel extract is: 100% ethanol, 70%, 40%, and water, tested against prostaglandin E2 synthesis and release of histamine. 40% ethanol extract showed the most potent effect in inhibiting histamine release from RBL 2H3- cell-mediated IgE. All mangosteen rind extract capable of inhibiting the synthesis of PGE2 from rat glioma cells induced Ca2 + ionophore A23187. In the passive cutaneous anaphylaxis reaction, all of mangosteen peel extract also shows the inhibitory activity of the reaction. From this study, 40% ethanol extract of mangosteen is the most potent in inhibiting PGE2 synthesis and release of histamine. 2. Anti-inflammatory Activity Research on anti-inflammatory activity of mangosteen rind until now only performed on the stages of in vitro and in vivo to a new stage in the study with rats induced karagenen method. From the research results suggested that compounds that have anti-inflammatory activity is gamma-mangostin. Gamma-mangostin is xanton diprenilasi tetraoksigenasi form, the chemical structure can be seen in Fig. Nakatni et al. (2002b) conducted a study of anti-inflammatory activity in vitro of gamma mangostin against PGE2 synthesis and cyclooxygenase (COX) in rat C6 glioma cells. Both the compound and the enzyme is an important mediator in the inflammatory reaction. Gamma-mangostin potently inhibit the release of PGE2 in rat C6 glioma cells induced Ca2 + ionophore A23187. Gammamangostin inhibit the conversion of arachidonic acid to PGE2 in the microsomal, there is a possibility of cyclooxygenase inhibition on track. In experiments in vitro enzymatic, this compound is able to inhibit the activity of the enzyme COX-1 and COX-2. However, these compounds have no significant effect on: (1) phosphorylation signal ekstraseuler p42 / p44 induced A23187, which regulates activated protein kinase kinase / mitogen, and (2) release of [14C] arachidonic -asam of cells labeled [14C ] the Aa. From this study, gamma mangostin has anti-inflammatory activity by inhibiting the activity of cyclooxygenase (COX). Furthermore, Nakatani et al. (2004) analyzed the effect of gamma-mangostin against COX-2 gene expression in rat C6 glioma cells. Gamma mangostin inhibits protein and mRNA expression of COX-2 induced by lipopolysaccharide, but no effect on protein expression of COX-1. Lipopolysaccharide serves to stimulate phosphorylation inhibitor kappaB (IkappaB) mediated IkappaB kinase, which then further degradation and induces nuclear translocation of NF-kappaB ligand that activates gene transcription of COX-2. In connection with that, it also inhibits gamma mangostin IkappaB kinase activity and decreases degradation IkappaB and LPS-induced phosphorylation. In luciferase reporter assay, the compound lowering the NF-kappaB activation induced by LPS and the process of gene transcription of COX-2-dependent gene promoter region of human COX-2. The findings are supported by the results of in vivo studies, gamma mangostin could inhibit inflammation-induced edema in rats karagenen. From this research can be made resume: gamma mangostin directly inhibit the enzyme activity Ikappa B kinase, to then prevent the COX-2 gene transcription (NFkappaB target genes), decrease the production of PGE2 in the inflammatory process. 3. Anti-oxidant Activity In Moongkarndi et al. (2004) reported that extracts of mangosteen rind potential as antioxidants. Furthermore, Weecharangsan et al. (2006) follow up on these results with the research activities of some antioxidant extracts of mangosteen rind is extract the water, 50 and 95% ethanol, and ethyl acetate. The method used is penangkatapan free radical 2,2-diphenyl-1-picrylhydrazyl. The results showed that all extracts have potential as free-radical scavengers, and water and ethanol extracts have greater potential. In connection with the antioxidant activity, the extracts were also able to demonstrate neuroprotective activity in cells NG108-15. Along with these results, Jung et al. (2006) conducted a study of antioxidant activity of all compounds contains mangosteen rind, minus mangostingon. From the results of the screening antioxidant activity of these compounds, which show potent activity are: 8-hidroksikudraxanton, gartanin, alpha-mangostin, gamma-mangostin and smeathxanton A. 4. Anticancer activity To date, cancer treatment is still unsatisfactory. Therefore, the study of cancer drug discovery are still intensively conducted. One of the medicinal plants that become the object of study is the mangosteen rind. Ho et al. (2002) managed to isolate and test compounds xanton cytotoxicity effects on liver cancer cell line. Based on these studies, a compound garsinon E showed the most potent cytotoxicity activity. Sementra it, Moongkarndi et al. (2004) reported that the methanol extract of mangosteen rind menunjukka highly potent activity in inhibiting the proliferation of breast cancer cells SKBR3, and showed apoptotic activity. On the other hand, Matsumoto et al. (2003) conducted a similar test that is anti-proliferative activity and apoptosis in human leukemia HL60 cell growth. Hasl In contrast to previous studies, alpha-mangostin showed anti-proliferative activity and apoptosis terpoten xanton among other compounds. In 2004, Matsumoto et al. The study went on to study the mechanism of apoptosis of alfamangostin. The compounds are able to activate the apoptotic enzyme caspase-3 and -9, but not in caspase-8. Alpha mangostin allegedly mem-mediated mitochondrial apoptosis pathway, is based on the change in the mitochondria after treatment of these compounds for 1-2 hours. Mitochondrial changes include: swelling of cells, reduced membrane potential, decrease in intracellular ATP, the accumulation of reactive oxygen species (ROS), and the release of c / AIF cytochrome cells. However, alpha-mangostin not affect the expression of bcl-2 family proteins and activation of MAP kinase. The results of these studies indicate that the target of the action of alpha-mangostin is the mitochondria in the early phase resulting in apoptosis in human leukemia cell line. From the structure activity relationship studies, the hydroxy group has contributed greatly to the apoptotic activity. Continuing the above findings, Nabandith et al. (2004) conducted a study in vivo chemopreventive activity of alpha-mangostin in lesions preneoplastik putative involved in colon carcinogenesis rats, induced a 1.2-dimetilhidrazin (DMH). Giving these compounds for 4-5 weeks, inhibit the induction and development of aberrant crypt foci (ACF), lowering dysplastic foci (DF) and betacatenin accumulated crypts (BCAC). On the nuclear antigen labeling of cells undergoing proliferation, these compounds reduce the occurrence of focal lesions and rat colonic epithelium. 5. Activities Antimikroorganisme Besides having some pharmacological activity as above, mangosteen rind also showed activity antimikroorganisme. Suksamrarn et al. (2003) with his team from Thailand, conduct research into the potential antituberkulosa of prenylated xanton compound isolated from the skin of the mangosteen fruit. As in the previous study, alpha mangostin, gamma-mangostin and garsinon B also showed the most potent activity in this experiment. All these compounds inhibit strong against Mycobacterium tuberculosis. The findings are followed up by researchers from Osaka, Japan, Sakagami et al. (2005). Focus on alpha-mangostin, this time the compound was isolated from the bark of the tree to obtain a large amount. Alfa mangostin active against enterococci and Staphylococcus aureus bacteria were respectively resistant and methicillin vancomisin. This was reinforced by the activity of synergism with some antibiotics (gentamicin and vancomisin) against both bacteria. Meanwhile, Mahabusarakam et al. (2006) conducted a test group xanton including mangostin, in Plasmodium falciparum. The results showed that mangostin has the effect antiplasmodial middle level, while xanton prenylated which has extremely potent inhibiting alkylamino group. 6. Other activities have already mentioned that alpha-mangostin has antioxidant activity and free radical scavengers. In connection with these facts, alpha-mangostin could inhibit the oxidation of low density lipoprotein (LDL), which was instrumental in atherosclerosis (William et al., 1995). While Mahabusarakam et al. (2000) reported that xanton prenylated can also inhibit the oxidation of LDL. Research lainnnya, mangostin reported to inhibit the potent against HIV-1 protease (Chen et al., 1996). Meanwhile, Gopalakrishnan et al. (1997) reported that the compound xanton mangostin from mangosteen fruit kuliat capable of inhibiting the growth of pathogenic fungi: Fusarium oxysporum vasinfectum, Alternaria tenuis, and Dreschlera oryzae. CHAPTER IV CLOSING A. Conclusion Based on the above presentation, it can be concluded that: 1. The mangosteen (Garcinia mangostana L.) is one of the plants used as traditional medicine. The skin of the mangosteen fruit is used to treat ulcers, dysentery, sore muscles and constipation. 2. Extraction of the withdrawal activity of chemical compounds that can dissolve so that apart from the insoluble material with a liquid solvent. By knowing the active compounds contained in crude drugs would facilitate the choice of solvent and extraction right (DITJEN POM, 2000). 3. The pharmacological activity contained in extracts of mangosteen rind including anti-inflammatory, antihistamine, treatment of heart disease, antibacterial, antifungal even for the treatment or therapy of HIV disease. The most active compounds in the skin of the mangosteen fruit is alpha-mangostin, gammamangostin and garsinon-EB Suggestion that I can say is: 1. Further studies should be conducted to examine the pharmacological effects of extracts of mangosteen rind with increasing concentration. 2. We recommend testing the toxicity of extract of mangosteen rind. REFERENCES Dungir, Stevi G., et al., 2012, Phenolic Antioxidant Activity of Skin Extract Mangosteen (Garcinia mangostana L.), the journal of Science Unsrat Online, volume 1, number 1, Department of Chemistry, Science Faculty, Unsrat, Manado. Indharini, Ulfah, 2010, Determination of Levels of Α-Mangostin In infuse Dry Skin Mangosteen (Garcinia Mangostana L.), thesis. Faculty of Pharmacy, University of Muhammadiyah Surakarta, Surakarta. Manurung, Sondra, et al., 2012, the Securities Antihiperglikemia of Extract Skin Mangosteen (Garcinia mangostana l.) Against Rats Male Strain Wistar (Rattus norvegicus l.) Induced by Sucrose, research, Laboratory of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Sam Ratulangi, Manado. Nugroho. Great. Endro. 2009. Mangosteen (Garcinia mangostana L.): Skin Fruit Of The Wasted Up Being A Drug Candidates. Laboratory of Pharmacology and Toxicology, Section of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Gadjah Mada. Jogjakarta. Pasaribu, Hidayani, et al., 2012, Ethanol Extracts Test Skin Mangosteen (Garcinia mangostana L.) Against Decrease Blood Glucose. Journal of Pharmaceutics and Pharmacology, Volume 1, Number 1, Faculty of Pharmacy, University of North Sumatra, North Sumatra. will stimulate mast cells to release histamine (Kresno, 2001; Subowo, 1993). Associated with allergic reactions or the release of histamine, Chairungsrilerd et al. (1996a, 1996b, 1998) to test the methanol extract of mangosteen rind to the contraction of isolated rabbit aorta chest induced by histamine and serotonin. From the analysis of the active components of the result of the continued fraction silica gel chromatography, indicating that the active compound is alpha and gamma mangostin. Alpha mangostin itself able to demonstrate the inhibitory activity contracted guinea pig isolated trachea and aorta piston isolated rabbit, induced cimetidine, histamine H2 receptor antagonists. However, these compounds do not show activity on the contraction induced karbakol, phenylephrine and KCl. Alpha mangostin was also able to inhibit binding of [3H] mepyramine against arta smooth muscle cells of rats. The latter compound is a specific antagonist for histamine H1 receptor. From the analysis of the kinetics of binding of [3H] mepyramine megnindikasikan that competitively inhibit alpha mangostin. This study suggests that alpha-mangostin is categorized as any blocks H1 receptors histaminergik particular, while gamma mangostin as any blocks serotonergic receptors, especially the 5-hydroxytryptamine 2A or 5HT2A. Furthermore, Nakatani et al. (2002a) conducted research into the mechanism toward the mangosteen rind extract. In the study of mangosteen peel extract is: 100% ethanol, 70%, 40%, and water, tested against prostaglandin E2 synthesis and release of histamine. 40% ethanol extract showed the most potent effect in inhibiting histamine release from RBL 2H3- cell-mediated IgE. All mangosteen rind extract capable of inhibiting the synthesis of PGE2 from rat glioma cells induced Ca2 + ionophore A23187. In the passive cutaneous anaphylaxis reaction, all of mangosteen peel extract also shows the inhibitory activity of the reaction. From this study, 40% ethanol extract of mangosteen is the most potent in inhibiting PGE2 synthesis and release of histamine. 2. Anti-inflammatory Activity Research on anti-inflammatory activity of mangosteen rind until now only performed on the stages of in vitro and in vivo to a new stage in the study with rats induced karagenen method. From the research results suggested that compounds that have anti-inflammatory activity is gamma-mangostin. Gamma-mangostin is xanton diprenilasi tetraoksigenasi form, the chemical structure can be seen in Fig. Nakatni et al. (2002b) conducted a study of anti-inflammatory activity in vitro of gamma mangostin against PGE2 synthesis and cyclooxygenase (COX) in rat C6 glioma cells. Both the compound and the enzyme is an important mediator in the inflammatory reaction. Gamma-mangostin potently inhibit the release of PGE2 in rat C6 glioma cells induced Ca2 + ionophore A23187. Gammamangostin inhibit the conversion of arachidonic acid to PGE2 in the microsomal, there is a possibility of cyclooxygenase inhibition on track. In experiments in vitro enzymatic, this compound is able to inhibit the activity of the enzyme COX-1 and COX-2. However, these compounds have no significant effect on: (1) phosphorylation signal ekstraseuler p42 / p44 induced A23187, which regulates activated protein kinase kinase / mitogen, and (2) release of [14C] arachidonic -asam of cells labeled [14C ] the Aa. From this study, gamma mangostin has anti-inflammatory activity by inhibiting the activity of cyclooxygenase (COX). Furthermore, Nakatani et al. (2004) analyzed the effect of gamma-mangostin against COX-2 gene expression in rat C6 glioma cells. Gamma mangostin inhibits protein and mRNA expression of COX-2 induced by lipopolysaccharide, but no effect on protein expression of COX-1. Lipopolysaccharide serves to stimulate phosphorylation inhibitor kappaB (IkappaB) mediated IkappaB kinase, which then further degradation and induces nuclear translocation of NF-kappaB ligand that activates gene transcription of COX-2. In connection with that, it also inhibits gamma mangostin IkappaB kinase activity and decreases degradation IkappaB and LPS-induced phosphorylation. In luciferase reporter assay, the compound lowering the NF-kappaB activation induced by LPS and the process of gene transcription of COX-2-dependent gene promoter region of human COX-2. The findings are supported by the results of in vivo studies, gamma mangostin could inhibit inflammation-induced edema in rats karagenen. From this research can be made resume: gamma mangostin directly inhibit the enzyme activity Ikappa B kinase, to then prevent the COX-2 gene transcription (NFkappaB target genes), decrease the production of PGE2 in the inflammatory process. 3. Anti-oxidant Activity In Moongkarndi et al. (2004) reported that extracts of mangosteen rind potential as antioxidants. Furthermore, Weecharangsan et al. (2006) follow up on these results with the research activities of some antioxidant extracts of mangosteen rind is extract the water, 50 and 95% ethanol, and ethyl acetate. The method used is penangkatapan free radical 2,2-diphenyl-1-picrylhydrazyl. The results showed that all extracts have potential as free-radical scavengers, and water and ethanol extracts have greater potential. In connection with the antioxidant activity, the extracts were also able to demonstrate neuroprotective activity in cells NG108-15. Along with these results, Jung et al. (2006) conducted a study of antioxidant activity of all compounds contains mangosteen rind, minus mangostingon. From the results of the screening antioxidant activity of these compounds, which show potent activity are: 8-hidroksikudraxanton, gartanin, alpha-mangostin, gamma-mangostin and smeathxanton A. 4. Anticancer activity To date, cancer treatment is still unsatisfactory. Therefore, the study of cancer drug discovery are still intensively conducted. One of the medicinal plants that become the object of study is the mangosteen rind. Ho et al. (2002) managed to isolate and test compounds xanton cytotoxicity effects on liver cancer cell line. Based on these studies, a compound garsinon E showed the most potent cytotoxicity activity. Sementra it, Moongkarndi et al. (2004) reported that the methanol extract of mangosteen rind menunjukka highly potent activity in inhibiting the proliferation of breast cancer cells SKBR3, and showed apoptotic activity. On the other hand, Matsumoto et al. (2003) conducted a similar test that is anti-proliferative activity and apoptosis in human leukemia HL60 cell growth. Hasl In contrast to previous studies, alpha-mangostin showed anti-proliferative activity and apoptosis terpoten xanton among other compounds. In 2004, Matsumoto et al. The study went on to study the mechanism of apoptosis of alfamangostin. The compounds are able to activate the apoptotic enzyme caspase-3 and -9, but not in caspase-8. Alpha mangostin allegedly mem-mediated mitochondrial apoptosis pathway, is based on the change in the mitochondria after treatment of these compounds for 1-2 hours. Mitochondrial changes include: swelling of cells, reduced membrane potential, decrease in intracellular ATP, the accumulation of reactive oxygen species (ROS), and the release of c / AIF cytochrome cells. However, alpha-mangostin not affect the expression of bcl-2 family proteins and activation of MAP kinase. The results of these studies indicate that the target of the action of alpha-mangostin is the mitochondria in the early phase resulting in apoptosis in human leukemia cell line. From the structure activity relationship studies, the hydroxy group has contributed greatly to the apoptotic activity. Continuing the above findings, Nabandith et al. (2004) conducted a study in vivo chemopreventive activity of alpha-mangostin in lesions preneoplastik putative involved in colon carcinogenesis rats, induced a 1.2-dimetilhidrazin (DMH). Giving these compounds for 4-5 weeks, inhibit the induction and development of aberrant crypt foci (ACF), lowering dysplastic foci (DF) and betacatenin accumulated crypts (BCAC). On the nuclear antigen labeling of cells undergoing proliferation, these compounds reduce the occurrence of focal lesions and rat colonic epithelium. 5. Activities Antimikroorganisme Besides having some pharmacological activity as above, mangosteen rind also showed activity antimikroorganisme. Suksamrarn et al. (2003) with his team from Thailand, conduct research into the potential antituberkulosa of prenylated xanton compound isolated from the skin of the mangosteen fruit. As in the previous study, alpha mangostin, gamma-mangostin and garsinon B also showed the most potent activity in this experiment. All these compounds inhibit strong against Mycobacterium tuberculosis. The findings are followed up by researchers from Osaka, Japan, Sakagami et al. (2005). Focus on alpha-mangostin, this time the compound was isolated from the bark of the tree to obtain a large amount. Alfa mangostin active against enterococci and Staphylococcus aureus bacteria were respectively resistant and methicillin vancomisin. This was reinforced by the activity of synergism with some antibiotics (gentamicin and vancomisin) against both bacteria. Meanwhile, Mahabusarakam et al. (2006) conducted a test group xanton including mangostin, in Plasmodium falciparum. The results showed that mangostin has the effect antiplasmodial middle level, while xanton prenylated which has extremely potent inhibiting alkylamino group. 6. Other activities have already mentioned that alpha-mangostin has antioxidant activity and free radical scavengers. In connection with these facts, alpha-mangostin could inhibit the oxidation of low density lipoprotein (LDL), which was instrumental in atherosclerosis (William et al., 1995). While Mahabusarakam et al. (2000) reported that xanton prenylated can also inhibit the oxidation of LDL. Research lainnnya, mangostin reported to inhibit the potent against HIV-1 protease (Chen et al., 1996). Meanwhile, Gopalakrishnan et al. (1997) reported that the compound xanton mangostin from mangosteen fruit kuliat capable of inhibiting the growth of pathogenic fungi: Fusarium oxysporum vasinfectum, Alternaria tenuis, and Dreschlera oryzae. CHAPTER IV CLOSING A. Conclusion Based on the above presentation, it can be concluded that: 1. The mangosteen (Garcinia mangostana L.) is one of the plants used as traditional medicine. The skin of the mangosteen fruit is used to treat ulcers, dysentery, sore muscles and constipation. 2. Extraction of the withdrawal activity of chemical compounds that can dissolve so that apart from the insoluble material with a liquid solvent. By knowing the active compounds contained in crude drugs would facilitate the choice of solvent and extraction right (DITJEN POM, 2000). 3. The pharmacological activity contained in extracts of mangosteen rind including anti-inflammatory, antihistamine, treatment of heart disease, antibacterial, antifungal even for the treatment or therapy of HIV disease. The most active compounds in the skin of the mangosteen fruit is alpha-mangostin, gammamangostin and garsinon-EB Suggestion that I can say is: 1. Further studies should be conducted to examine the pharmacological effects of extracts of mangosteen rind with increasing concentration. 2. We recommend testing the toxicity of extract of mangosteen rind. REFERENCES Dungir, Stevi G., et al., 2012, Phenolic Antioxidant Activity of Skin Extract Mangosteen (Garcinia mangostana L.), the journal of Science Unsrat Online, volume 1, number 1, Department of Chemistry, Science Faculty, Unsrat, Manado. Indharini, Ulfah, 2010, Determination of Levels of Α-Mangostin In infuse Dry Skin Mangosteen (Garcinia Mangostana L.), thesis. Faculty of Pharmacy, University of Muhammadiyah Surakarta, Surakarta. Manurung, Sondra, et al., 2012, the Securities Antihiperglikemia of Extract Skin Mangosteen (Garcinia mangostana l.) Against Rats Male Strain Wistar (Rattus norvegicus l.) Induced by Sucrose, research, Laboratory of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Sam Ratulangi, Manado. Nugroho. Great. Endro. 2009. Mangosteen (Garcinia mangostana L.): Skin Fruit Of The Wasted Up Being A Drug Candidates. Laboratory of Pharmacology and Toxicology, Section of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Gadjah Mada. Jogjakarta. Pasaribu, Hidayani, et al., 2012, Ethanol Extracts Test Skin Mangosteen (Garcinia mangostana L.) Against Decrease Blood Glucose. Journal of Pharmaceutics and Pharmacology, Volume 1, Number 1, Faculty of Pharmacy, University of North Sumatra, North Sumatra.
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