Mangosteen

Scientific Name(s): Garcinia mangostana Family: Guttiferae

Common Name(s): Mangosteen , mangostan , “queen of the tropical fruits.”

Uses

Mangosteen possesses possible antioxidant, anti-inflammatory, anticancer, and antihistamine properties, but clinical trials data are lacking.

Dosing

Mangosteen is available in capsule, tablet, beverage, and cream forms. The typical dose is 500 mg by mouth twice a day. The beverages are dosed as 30 mL per day.

Contraindications

Avoid use with coexisting hypersensitivity.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

One case report documents a 58-year-old man ingesting mangosteen juice daily for 12 months as a dietary supplement who developed severe lactic acidosis.

Toxicology

No toxicity studies have been reported in humans.

Botany

The genus Garcinia comprises nearly 400 species of evergreen trees and shrubs. Mangosteen is a slow-growing and shallow-rooted evergreen tree reaching up to 25 m in height. The leaves are thick and leathery, while the flowers are fleshy and 4 to 5 cm in diameter. The flowers are often green on the outside and yellow to red on the inside, with 4 sepals and 4 petals. Many of the species of the Guittiferae family bear edible fruit; however, mangosteen is the most valued tropical fruit. 1 , 2 , 3

The fruit is round, 2.5 to 7.5 cm in diameter, and weighs about 75 to 150 g. The rind is smooth and 0.6 to 1 cm thick. The exterior is pale green when immature and dark purple when fully ripe. The inner pulp contains 4 to 8 juicy white segments that are sweet and faintly aromatic. The fruits may or may not contain seeds. 1 , 2 , 3

Mangosteen is thought to be native to Southeast Asia or Indonesia and remains largely indigenous to the Malay Peninsula, Myanmar, Thailand, Cambodia, Vietnam, and the Moluccas. During the past 2 centuries, mangosteen has been cultivated in tropical areas such as India, Honduras, Brazil, and Australia. The species thrives in warm and humid or tropical climates and has a narrow range of adaptability. 1 , 2 , 3

Mangosteen species are of economic and commercial interest, with tremendous demand for the fruit in domestic and export markets. Thailand is responsible for approximately 85% of the total production of 150,000 tons per year. Malaysia and Indonesia are also major commercial producing countries. In the United States alone, mangosteen juice sales for 2007 were estimated at $98 million. Depending on the growth cycle, a single tree may produce 500 to 800 fruits in one year. Other commercial uses include landscape material (the crown) and natural dye for cotton and silk yarn. 1 , 2 , 3 , 4 , 5

History

The rind, leaves, fruit, and bark of mangosteen have been used in folk medicine for thousands of years. The rind has been used medicinally to treat thick mucus, cystitis, diarrhea, dysentery, fever, as well as intestinal and skin ailments, such as eczema and pruritus. 2 , 3 , 6 , 7 , 8 , 9 , 10

The leaves are used in traditional medicine in teas for treating diarrhea, dysentery, fever, and thrush. 2 , 3

Concentrates of mangosteen bark have been used medicinally to treat genitourinary disorders, including gonorrhea and stomatosis. 2 , 3 , 10

Chemistry

Numerous studies 9 , 11 , 12 , 13 , 14 have found high concentrations of xanthones, a class of polyphenolic compounds, in mangosteen. Xanthones have antioxidant, antibacterial, antifungal, anti-inflammatory, antitumor, antiplatelet aggregation, antithrombotic, and vasorelaxant activities, prevent oxidative damage of low-density lipoprotein, histamine, and serotonin receptor blocker activity, and inhibit HIV. 9 The xanthones and tannins of the mangosteen pericarp protect against insects, fungi, plant viruses, bacteria, and animals while the fruit is still immature. Of the 200 known xanthones, nearly 50 are found in mangosteen. 2 The major xanthones are alpha-mangostin, beta-mangostin, gamma-mangostin, and methoxy-beta-mangostin, 2 and the most abundant is alpha-mangostin. 3 , 9 Calcium, phosphorus, iron, thiamine, riboflavin, niacin, and ascorbic acid are found in mangosteen.

Uses and Pharmacology

Antioxidant
In vitro data

The phenolic compounds from the hull of mangosteen have strong antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity assays. 10 One study documents neuroprotective activity of extracts of the fruit hull. 15 Similar studies document the antioxidant and ferric-reducing activity of mangosteen compared with various fruits. 16 , 17

Animal data

A study in rats fed high cholesterol diets notes the positive effects on plasma lipid levels and plasma antioxidant activity for mangosteen. 18

Clinical data

A 60-day study with 20 healthy women found improvement of age-related changes in skin smoothness with cream containing 3 antioxidants, including mangosteen, compared with placebo cream. 19

Antihistamine
In vitro data

Several studies found potent inhibitory activity on both histamine release and prostaglandin E 2 synthesis by mangosteen fruit extract. The xanthones alpha-mangostin and gamma-mangostin are histaminergic and serotonergic receptor blocking agents. 20 , 21 Alpha-mangostin is a selective and competitive H 1 receptor antagonist, while gamma-mangostin is a selective and competitive 5-HT 2A receptor antagonist. 22 , 23 Alpha-, beta-, and gamma-mangostin suppressed the upstream degranulation (release of allergic mediators) process in rat basophilic leukemia cells. 24

Inflammation
In vitro data

The xanthone, gamma-mangostin, potently inhibited prostaglandin E 2 (PGE 2 ) release and competitively inhibited the activities of both COX-1 and COX-2 enzymes in C6 rat glioma cells. These enzymes are major mediators in regulating inflammation. 25 Gamma-mangostin also inhibited IkappaB kinase activity associated with expression of the COX-2 enzyme. 26 In addition, alpha-mangosteen has potent inhibitory activity against prostaglandin PGE 2 release. 27 Alpha- and gamma-mangostins both inhibited nitrite production of lipopolysaccharide activated macrophage cells. 28

Cancer
In vitro data

Alpha-mangostin, mangostanol, and garcinone D extracts from the stem and root bark of G. mangostana were cytotoxic against the CEM-SS cell line. 29 , 30

The efficacy and potency of garcinone E, a xanthone from mangosteen, was compared with 6 chemotherapeutic drugs used to treat 4 hepatoma cell lines. Garcinone E is equal to or more potent than mitoxantrone in cytotoxicity against the hepatoma cell lines and may be more effective than methothrexate, vincristine, 5-fluorouracil (5-FU), and cisplatin. 31

Six xanthones were extracted from the pericarps of mangosteen and examined for cell growth inhibition of the human leukemia cell line HL60. All xanthones had documented growth inhibitory effects, but alpha-mangostin showed the most potent inhibitory activity. 32 The mechanism of action is associated with alpha-mangostin activating caspase-9 and -3 but not -8, and mediating the mitochondrial pathway in the apoptosis. 33 , 34

Alpha-mangostin induced growth inhibition in DLD-1 human colon cancer cells with potency similar to 5-FU. The mechanism of action of xanthones from mangosteen is associated with cell-cycle arrest by affecting expression of cyclins, cdc2, and p27; G1 cell cycle arrest by alpha-mangostin and beta-mangostin, and S cycle arrest by gamma-mangostin. Alpha-mangostin also induces apoptosis that is mediated by the intrinsic pathway through mitochondria and modulates growth-related signal transduction pathways. 2 Another study noted a synergistic growth reduction in human colon cancer DLD-1 cells with combined treatment of alpha-mangostin and 5-FU. 35

In one study, an extract from the pericarp of mangosteen inhibited the growth of breast cancer cells through apoptosis. 36 In another experiment, alpha-mangostin exhibited the most potent effects among the isolates studied. 37

Animal data

A rat study on putative preneoplastic lesions in rat colon carcinogenesis found that dietary administration of alpha-mangostin inhibited the development of aberrant crypt foci ( P < 0.05 for 0.02% crude alpha-mangostin, P < 0.01 for 0.05% crude alpha-mangostin). Rats treated with 0.05% crude alpha-mangostin had decreased dysplastic foci ( P < 0.05) and beta-catenin accumulated crypts ( P < 0.05). 38

Chemotherapeutic
In vitro data

Several xanthones isolated from the fruit hulls of mangosteen have antifungal activity against 3 phytopathogenic fungi, Fusarium oxysporum vasinfectum , Alternaria tenuis , and Dreschlera oryzae . 6 Mangosteen also has activity against the dermatophytes Trichophyton mentagrophytes , Microsporum gypseum , and Epidermophyton floccosum . 39 , 40

Mangosteen has strong antibacterial activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus . 41 Alpha-mangostin, from the stem bark of mangosteen, was active against vancomycin-resistant Enterococci and methicillin-resistant S. aureus , with minimum inhibitory concentration (MIC) values of 6.25 to 12.5 mcg/mL. 42 Activity against acne-inducing bacteria Propionibacterium acnes and Staphylococcus epidermidis is also documented. 8 , 43

The xanthones, alpha- and beta-mangostins and garcinone B, isolated from the fruit hulls and the edible arils and seeds of mangosteen exhibited strong inhibitory activity against Mycobacterium tuberculosis with a MIC value of 6.25 mcg/mL. 7

Prenylated xanthones from mangosteen exhibited potent antiplasmodial activity against Plasmodium falciparum . 44

Clinical data

One study of 60 participants found that an herbal mouthwash containing the pericarp extract of mangosteen may be used, in addition to other treatment, for improving oral malodor. 45

Other pharmacologic activity
GI disorders

The xanthones from mangosteen may be useful in treating Helicobacter pylori digestive tract disorders such as peptic ulcer, gastritis, and gastric cancer. 46

Heart disease

A study in rats documents the efficacy of alpha-mangostin against cardiotoxicity and beta-adrenergic catecholamine-induced myocardial toxicity and oxidative stress. 47 Mangosteen also inhibits oxidative changes in human LDL by acting as a free radical scavenger to protect LDL. 48 , 49

HIV

Noncompetitive inhibition is documented for mangostin and gamma-mangostin against HIV-1 protease. 50

Dosage

Mangosteen is available in capsule, tablet, beverage, and cream forms. The typical dose is 500 mg by mouth twice a day. Beverages are dosed as 30 mL per day. Numerous patents exist on mangosteen nutraceutical applications in beverages, 51 , 52 animal products, 53 and cosmetic and dermatological preparations. 54 , 55

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Mangosteen products have antioxidant activity and may interact with chemotherapeutic drugs such anthracyclines, platinum compounds, and alkylating agents. Patients taking antihistamines may note an additive affect with mangosteen.

Adverse Reactions

Use should be avoided with hypersensitivity to any of the constituents in mangosteen. People with diabetes should be aware of the high sugar content in mangosteen juice. Theoretically, mangosteen may interfere with the action of certain chemotherapeutic drugs and radiation therapy.

Severe lactic acidosis was reported in a 58-year-old man ingesting mangosteen juice daily for 12 months, possibly resulting from alpha-mangostin associated mitochondrial dysfunction. 56

Toxicology

No toxicity studies have been reported in humans. In one experiment, the seed oil was not found to be toxic to the liver, heart, or spleen when fed to rats. Kidney lesions observed in some rats were mild and not limited to the test rats. 57

Bibliography

1. Ramage CM, Sando L, Peace CP, Carroll BJ, Drew RA. Genetic diversity revealed in the apomictic fruit species Garcinia mangostana L. (mangosteen). Euphytica . 2004;136:1-10.
2. Akao Y, Nakagawa Y, Iinuma M, Nozawa Y. Anti-cancer effects of xanthones from pericarps of mangosteen. Int J Mol Sci . 2008;9:355-370.
3. Chin YW, Jung HA, Chai H, Keller WJ, Kinghorn AD. Xanthones with quinone reductase-inducing activity from the fruits of Garcinia mangostana (mangosteen). Phytochemistry . 2008;69(3):754-758.
4. HerbalGram . Herbal supplement sales in United States show growth in all channels. 2008;78:60-63.
5. Chairat M, Bremner JB, Chantrapromma K. Dyeing of cotton and silk yarn with the extracted dye from the fruit hulls of mangosteen, Garcinia mangostana linn. Fibers Polym . 2007;8(6):613-619.
6. Gopalakrishnan G, Banumathi B, Suresh G. Evaluation of the antifungal activity of natural xanthones from Garcinia mangostana and their synthetic derivatives. J Nat Prod . 1997;60(5):519-524.
7. Suksamrarn S, Suwannapoch N, Phakhodee W, et al. Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia mangostana . Chem Pharm Bull (Tokyo) . 2003;51(7):857-859.
8. Chomnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan W. Effect of Garcinia mangostana on inflammation caused by Propionibacterium acnes . Fitoterapia . 2007;78(6):401-408.
9. Ji X, Avula B, Khan IA. Quantitative and qualitative determination of six xanthones in Garcinia mangostana L. by LC-PDA and LC-ESI-MS. J Pharm Biomed Anal . 2007;43(4):1270-1276.
10. Yu L, Zhao M, Yang B, Zhao Q, Jiang Y. Phenolics from hull of Garcinia mangostana fruit and their antioxidant activities. Food Chem . 2007;104(1):176-181.
11. Mahabusarakam W, Wiriyachitra P, Taylor WC. Chemical constituents of Garcinia mangostana . J Nat Prod . 1987;50(3):474-478.
12. Nilar, Harrison LJ. Xanthones from the heartwood of Garcinia mangostana . Phytochemistry . 2002;60(5):541-548.
13. Nilar, Nguyen LH, Venkatraman G, Sim KY, Harrison LJ. Xanthones and benzophenones from Garcinia griffithii and Garcinia mangostana . Phytochemistry . 2005;66(14):1718-1723.
14. Fu C, Loo AE, Chia FP, Huang D. Oligomeric proanthocyanidins from mangosteen pericarps. J Agric Food Chem . 2007;55(19):7689-7694.
15. Weecharangsan W, Opanasopit P, Sukma M, Ngawhirunpat T, Sotanaphun U, Siripong P. Antioxidative and neuroprotective activities of extracts from the fruit hull of mangosteen ( Garcinia mangostana Linn.). Med Princ Pract . 2006;15(4):281-287.
16. Okonogi S, Duangrat C, Anuchpreeda S, Tachakittirungrod S, Chowwanapoonpohn S. Comparison of antioxidant capacites and cytotoxicities of certain fruit peels. Food Chem . 2007;103(3):839-846.
17. Patthamakanokporn O, Puwastien P, Nitithamyong A, Sirichakwal PP. Changes of antioxidant activity and total phenolic compounds during storage of selected fruits. J Food Compost Anal . 2008;21(3):241-248.
18. Leontowicz M, Leontowicz H, Drzewiecki J, Jastrzebski Z, Haruenkit R, Poovarodom S. Two exotic fruits positively affect rats plasma composition. Food Chem . 2007;102(1):192-200.
19. Hsu J, Skover G, Goldman MP. Evaluating the efficacy in improving facial photodamage with a mixture of topical antioxidants. Drugs in Dermatol . 2007;6(11):1141-1148.
20. Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y. Histaminergic and serotonergic receptor blocking substances from the medicinal plant Garcinia mangostana . Planta Med . 1996;62(5):471-472.
21. Nakatani K, Atsumi M, Arakawa T, et al. Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen, a Thai medicinal plant. Biol Pharm Bull . 2002;25(9):1137-1141.
22. Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y. Pharmacological properties of alpha-mangostin, a novel histamine H1 receptor antagonist. Eur J Pharmacol . 1996;314(3):351-356.
23. Furukawa K, Chairungsrilerd N, Ohta T, Nozoe S, Ohizumi Y. Novel types of receptor antagonists from the medicinal plant Garcinia mangostana .[in Japanese]. Nippon Yakurigaku Zasshi . 1997;110 (suppl) 1:153P-158P.
24. Itoh T, Ohguchi K, Iinuma M, Nozawa Y, Akao Y. Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation. Bioorg Med Chem . 2008;16(8):4500-4508.
25. Nakatani K, Nakahata N, Arakawa T, Yasuda H, Ohizumi Y. Inhibition of cyclooxygenase and prostaglandin E2 synthesis by gamma-mangostin, a xanthone derivative in mangosteen, in C6 rat glioma cells. Biochem Pharmacol . 2002;63(1):73-79.
26. Nakatani K, Yamakuni T, Kondo N, et al. Gamma-mangostin inhibits inhibitor-kappaB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells. Mol Pharmacol . 2004;66(3):667-674.
27. Chen LG, Yang LL, Wang CC. Anti-inflammatory activity of mangostins from Garcinia mangostana . Food Chem Toxicol . 2008;46(2):688-693.
28. Wang CC, Chen LG, Lin LH, Yang LL. Inducible nitric oxide synthase inhibitors of Chinese herbs IV: Garcinia mangostana . American Chemical Society . 2004;AN 2004:655096.
29. Ee GCL, Izzaddin SA, Rahmani M, Sukari MA, Lee HL. Gamma-mangostin and rubraxanthone, two potential lead compounds for anti-cancer activity against CEM-SS cell line. Nat Prod Sci . 2006;12(3):138-143.
30. Ee GC, Daud S, Izzaddin SA, Rahmani M. Garcinia mangostana : a source of potential anti-cancer lead compounds against CEM-SS cell line. J Asian Nat Prod Res . 2008;10(5-6):475-479.
31. Ho CK, Huang YL, Chen CC. Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. Planta Med . 2002;68(11):975-979.
32. Matsumoto K, Akao Y, Kobayashi E, et al. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J Nat Prod . 2003;66(8):1124-1127.
33. Chiang LC, Cheng HW, Liu MC, Chiang W, Chun-Ching Lin CC. In vitro evaluation of antileukemic activity of 17 commonly used fruits and vegetables in Taiwan. Lebensm Wiss Technol . 2004;37(5):539-544.
34. Matsumoto K, Akao Y, Yi H, et al. Preferential target is mitochondria in alpha-mangostin-induced apoptosis in human leukemia HL60 cells. Bioorg Med Chem . 2004;12(22):5799-5806.
35. Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y. Characterized mechanism of alpha-mangostin-induced cell death: caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells. Bioorg Med Chem . 2007;15(16):5620-5628.
36. Moongkarndi P, Kosem N, Kaslungka S, Luanratana O, Pongpan N, Neungton N. Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol . 2004;90(1):161-166.
37. Suksamrarn S, Komutiban O, Ratananukul P, Chimnoi N, Lartpornmatulee N, Suksamrarn A. Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana . Chem Pharm Bull (Tokyo) . 2006;54(3):301-305.
38. Nabandith V, Suzui M, Morioka T, et al. Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat. Asian Pac J Cancer Prev . 2004;5(4):433-438.
39. Mahabusarakam W, Phongpaichit S, Wiriyachitra P. Screening of antifungal activity of chemicals from Garcinia mangostana . Warasan Songkhia Nakkharin . 1983;5(4):341-342.
40. Mahabusarakam W, Wiriyachitra P, Phongpaichit S. Antimicrobial activities of chemical constituents from Garcinia mangostana Linn. J Sci Soc Thailand . 1986;12(4):239-243.
41. Iinuma M, Tosa H, Tanaka T, et al. Antibacterial activity of xanthones from guttiferaeous plants against methicillin-resistant Staphylococcus aureus . J Pharm Pharmacol . 1996;48(8):861-865.
42. Sakagami Y, Iinuma M, Piyasena KG, Dharmaratne HR. Antibacterial activity of alpha-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics. Phytomedicine . 2005;12(3):203-208.
43. Chomnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan W. Antimicrobial effects of Thai medicinal plants against acne-inducing bacteria. J Ethnopharmacol . 2005;101(1-3):330-333.
44. Mahabusarakam W, Kuaha K, Wilairat P, Taylor WC. Prenylated xanthones as potential antiplasmodial substances. Planta Med . 2006;72(10):912-916.
45. Rassameemasmaung S, Sirikulsathean A, Amornchat C, Hirunrat K, Rojanapanthu P, Gritsanapan W. Effects of herbal mouthwash containing the pericarp extract of Garcinia mangostana L on halitosis, plaque and papillary bleeding index. J Int Acad Periodontol . 2007;9(1):19-25.
46. Hasegawa H, Sakai S, Aimi N, Takayama H, Koyano T. Helicobacter pylori inhibitors containing xanthones from Garcinia mangostana . Kokai Tokkyo Koho Jpn . 1996;AN 1996:707533.
47. Sampath PD, Vijayaragavan K. Ameliorative prospective of alpha-mangostin, a xanthone derivative from Garcinia mangostana against beta-adrenergic cathecolamine-induced myocardial toxicity and anomalous cardiac TNF-alpha and COX-2 expressions in rats. Exp Toxicol Pathol . 2008;60(4-5):357-364.
48. Williams P, Ongsakul M, Proudfoot J, Croft K, Beilin L. Mangostin inhibits the oxidative modification of human low density lipoprotein. Free Radic Res . 1995;23(2):175-184.
49. Li P. Garcinia mangostana pericarp extract, its extraction and medical application. Faming Zhuanli Shenqing Gongkai Shuomingshy . AN 2006:1003483.
50. Chen SX, Wan M, Loh BN. Active constituents against HIV-1 protease from Garcinia mangostana . Planta Med . 1996;62(4):381-382.
51. Fugal KB, Mccausland TL, Kou X, Keller WJ, inventors; Neutraceutical composition containing mangosten pericarp extract. US patent application 2004-975243. October 27, 2004. http://www.uspto.gov .
52. Garrity AR, Morton JC, Morrison P, De La Huerga V. Nutraceutical mangosteen tea. Planta Med . 1996;62(4):381-382.
53. Wadsworth JW, Story SP, Zhou BN, et al, inventors; Garcinia mangostana L. enhanced animal food product. AN 2006:408789. 2006. http://www.uspto.gov .
54. Moffett A, Shah P, inventors; Pharmaceutical, therapeutic, nutritional, cosmetic, and dermatological compositions derived from Garcinia manostana L. plant. AN 2006:470299. 2006. http://www.uspto.gov .
55. Gupta SK, inventor; Skin firming anti-aging cosmetic compositions. US patent application 2003-248753. February 14, 2003. http://www.uspto.gov .
56. Wong LP, Klemmer PJ. Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana . Am J Kidney Dis . 2008;51(5):829-833.
57. Ajayi IA, Oderinde RA, Ogunkoya BO, Egunyomi A, Taiwo VO. Chemical analysis and preliminary toxicological evaluation of Garcinia mangostana seeds and seed oil. Food Chem . 2007;101(3):999-1004.

Copyright © 2009 Wolters Kluwer Health

Hide
(web2)