This action might not be possible to undo. Are you sure you want to continue?
Contents lists available at ScienceDirect
Food and Chemical Toxicology
journal homepage: www.elsevier.com/locate/foodchemtox
Medicinal properties of mangosteen (Garcinia mangostana)
José Pedraza-Chaverri *, Noemí Cárdenas-Rodríguez, Marisol Orozco-Ibarra, Jazmin M. Pérez-Rojas
Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, 04510 Mexico, DF, Mexico
a r t i c l e
i n f o
a b s t r a c t
Many tropical plants have interesting biological activities with potential therapeutic applications. Garcinia mangostana Linn. (GML) belongs to the family of Guttiferae and is named ‘‘the queen of fruits”. It is cultivated in the tropical rainforest of some Southeast Asian nations like Indonesia, Malaysia, Sri Lanka, Philippines, and Thailand. People in these countries have used the pericarp (peel, rind, hull or ripe) of GML as a traditional medicine for the treatment of abdominal pain, diarrhea, dysentery, infected wound, suppuration, and chronic ulcer. Experimental studies have demonstrated that extracts of GML have antioxidant, antitumoral, antiallergic, anti-inﬂammatory, antibacterial, and antiviral activities. The pericarp of GML is a source of xanthones and other bioactive substances. Prenylated xanthones isolated from GML have been extensively studied; some members of these compounds possess antioxidant, antitumoral, antiallergic, anti-inﬂammatory, antibacterial, antifungal and antiviral properties. Xanthones have been isolated from pericarp, whole fruit, heartwood, and leaves. The most studied xanthones are a-, b-, and c-mangostins, garcinone E, 8deoxygartanin, and gartanin. The aim of this review is to summarize ﬁndings of beneﬁcial properties of GML’s extracts and xanthones isolated from this plant so far. Ó 2008 Elsevier Ltd. All rights reserved.
Article history: Received 14 May 2008 Accepted 25 July 2008
Keywords: Garcinia mangostana Mangosteen Xanthones Medicinal properties
Contents 1. 2. 3. 4. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xanthones isolated from the pericarp of mangosteen-fruit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xanthones from whole fruit, trunk, branches, and leaves of GML . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Main biological and medicinal properties of GML . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Antioxidant properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Antitumoral properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Anti-inflammatory and antiallergy properties. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4. Antibacterial, antifungal and antiviral properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5. Antimalarial properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Medicinal properties of xanthones isolated from sources other than G. Mangostana . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3228 3228 3232 3232 3232 3233 3234 3236 3237 3237 3237 3237 3237 3237
Abbreviations: ABTS, 2,20-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid); BHA, butylated hydroxyanisole; BHT, butylated hydroxytoluene; CAT, catalase; CD, concentration required to double QR induction activity; CNS, central nervous system; COX, cyclooxygenase; CPK, creatine phosphokinase; DHR-123, dihydrorhodamine 123; LD50, lethal dose 50%; DMH, 1,2-dimethylhydrazine; DMBA, 7,12-dimethylbenz[a]anthracene; DPPH, 2,2-diphenyl-1-picrylhydrazyl; ED50, effective dose in 50% of the test organisms; 5-FMT, 5-ﬂuoro-a-methyltryptamine; 5-FU, 5-ﬂuorouracil; GOT, glutamate oxoloacetate transaminase; GSH, reduced glutathione; GML, Garcinia mangostana Linn.; H2O2, hydrogen peroxide; GPx, glutathione peroxidase; GPT, glutamate pyruvate transaminase; GST, glutathione-S-transferase; 5-HT, 5-hydroxytryptamine; HIV-1, human immunodeﬁcience virus; HOÅ, hydroxyl radical; IC50, inhibitory concentration at 50%; LDH, lactate dehydrogenase; LDL, low density lipoprotein; LOX, lipoxygenase; LPS, lypopolisaccharide; M, a-mangostin; 1M, 1-isomangostin; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; MT, mangostin À triacetate; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; NOÅ, nitric oxide; iNOS, inducible nitric oxide sintase; ONOOÀ, peroxynitrite; OÅ 2 , superoxide anion; PGE2, prostaglandin-E2, PML, polymorphonuclear leucocyte; QR, quinone reductase; ROS, reactive oxygen species; SOD, superoxide dismutase; TBARS, thiobarbituric reactive substances; VRE, vancomycin resistant Enterococci. * Corresponding author. Tel./fax: +52 55 5622 3878. E-mail address: email@example.com (J. Pedraza-Chaverri). 0278-6915/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.fct.2008.07.024
(1956). antibacterial. glabrous leaves and is slow to grow (Morton. cystitis and urethra suppuration Mouth aphthae Fever Amoebic dysentery Eczemab Acnec Thrush Abdominal pain Suppuration Leucorrhoea Cholera Convulsants a b c References Garnett and Sturton (1932). Mangosteen is known as ‘‘the queen of fruits” because it is one of the best tasting tropical fruits. 2005). Currently. Jefferson (1970) and Govindachari and Muthukumaraswamy (1971) also isolated a. In Ayurvedic medicine the pericarp of mangosteen-fruit has wide use against inﬂammation and diarrhea (Balasubramanian and Rajagopalan. (1980a) Malawska (2005) Pericarp poultice. 1932. The pericarp of mangosteen-fruit has been used as a medicinal agent by Southeast Asians for centuries in the treatment of skin infections and wounds (Mahabusarakam et al. Philippines. Local use as ointment.... 2000. (c) prenylated xanthones. amoebic dysentery (Garnett and Sturton.. Malaysia... Later. Pierce. antitumoral. Vieira and Kijjoa. 1992. and they comprise an important class of oxygenated heterocycles. 2005). mangosharin was isolated from the bark of GML (Ee et al. Wan (1973) and Pierce (2003) Mahabusarakam et al. Morton (1987) and Yates and Stout (1958) Caius (2003) and Morton (1987) Morton (1987) Saralamp et al. 2006). Gales and Damas. 19 fungi species and 3 lichens species. with white. 1855). Xanthones have been classiﬁed in ﬁve groups: (a) simple oxygenated xanthones.and b-mangostins. Peres et al.and c-mangostins. 1970). bark. Cosmetic cream.. 1987). Chopra et al. and Thailand. Sultanbawa. (1996) and Harbone et al. Pedraza-Chaverri et al. Xanthones or xanthen-9H-ones are secondary metabolites found in some higher plant families. Yates and Stout (1958) established the molecular formula. This tree can reach 6–25 m and it has leathery. 2004). Xanthones have been isolated from pericarp. (2005) Morton (1987) Moongkarndi et al. The xanthone nucleus is known as 9-xanthenone or dibenzo-c-pyrone and it is symmetric (Fig. Chopra et al. whole fruit.3228 J. 8deoxygartanin and gartanin are the most studied xanthones. . 1) (Schmid. (1996) Saralamp et al.. 1968). 1971. 2003). and cholera and dysentery (Sen et al. Sri Lanka. the structure of which was not elucidated until 1968 (Yates and Bhat. Jiang et al.9-dihydroxy-8-methoxy-2. and type and position of substituents of amangostin. 1980b). 1988). Pinto et al. 1987. antifungal and antiviral are some of the reported activities of xanthones isolated from GML which are discussed in the present review. 2004. / Food and Chemical Toxicology 46 (2008) 3227–3239 1.. (b) xanthone glycosides. Dragendorff (1930) isolated b-mangostin.) (GML) is a tropical tree from India. It is a yellow coloring matter that can also be obtained from bark and dried sap of GML (Dragendorff. 2006) and a.. Peres and Nagem.. Xanthones isolated from the pericarp of mangosteen-fruit Fifty xanthones have been isolated from pericarp mangosteenfruit (Table 2). (1996). Dragendorff (1930) and Murakami (1932) elucidated the mangostin structure. Morton (1987) and Moongkarndi et al. which is a shrub tree belonging to the Guttiferae family (Laphookhieo et al.. (2006) Saralamp et al.and b-mangostins were isolated from the root of Cratoxylum cochinchinense. Chairungsrilerd et al. (1999) and Suksamrarn et al.. a-. (1999) Caius (2003) Garnett and Sturton (1932). 2. Myanmar. 2006). fungi and lichens (Peres et al. In addition. 2006). antiallergy. 1989. Souza and Pinto. Morton (1987) and Yates and Stout (1958) Garnett and Sturton (1932). (2004a) Caius (2003) Caius (2003). Furthermore. 2005). (1973) Pierce (2003) Pierce (2003) Pierce (2003) Mahabusarakam et al. Bennett and Lee. etc. Introduction Mangosteen (Garcinia mangostana Linn. (2004a) Moongkarndi et al. (1992) Harbone et al. 278 new xanthones were identiﬁed between 2000 and 2004 (Vieira and Kijjoa. GML has been shown to contain a variety of secondary metabolites such as prenylated and oxygenated xanthones (Govindachari and Muthukumaraswamy. 1) (Vieira and Kijjoa.b) and Harbone et al. Mandal et al. (d) xanthonolignoids and (e) miscellaneous xanthones (Sultanbawa. 1956). 2005. The biological activities of this class of com- pounds are associated with their tricyclic scaffold but vary depending on the nature and/or position of the different substituents (Souza and Pinto. (see Table 1). gartanin and 8-deoxygartanin (Govindachari and Muthukumaraswamy. 5. b. 2000). 1996). 1971). Recently. 2005. 2005.2-dimethyl-7-isopre- Table 1 Traditional medicinal properties of Garcinia mangostana Illness Dysentery Diarrhea and chronic diarrhea in adults and children Haemorrhoids Food allergies Arthritisa Woundsa Skin infections Tuberculosis Inﬂammation Ulcers Micosis Affections of the genito-urinary tracts Gonorrhea. (2004a) Sen et al. Antioxidant. (1996a.. (1956). synthetic xanthones have been used in several studies. 2005). Several studies have shown that xanthones obtained from mangosteen-fruit have remarkable biological activities (Suksamrarn et al. Morton (1987) and Wan et al. 1987). From 20 higher plant families (122 species in 44 genus). anti-inﬂammatory. 1930). (1999) Harbone et al. Pierce (2003) and Jinsart et al. The mangosteen-fruit is dark purple or reddish. (1987). (1999) and Hasegawa et al. soft and juicy edible pulp with a slightly acid and sweet ﬂavor and a pleasant aroma (Jung et al. and leaves of GML. (1986. Chopra et al. Jiang et al. approximately 1000 different xanthones have been described (Souza and Pinto. (1996) and Chomnawang et al. The ﬁrst of them was named mangostin (after it was named a-mangostin) when it was isolated in 1855 (Fig. Other xanthones that have been isolated from the pericarp of mangosteen-fruit are c-mangostin (Jefferson et al. 1980. (2004a) Moongkarndi et al. garcinone E. 1980. 2005.
. 1980a. 2001). 2-isoprenyl-220.127.116.11-dihydroxy2-isoprenyl-3-methoxyxanthone. 1972). Sen et al. 1995).7-dihydroxy-2-isoprenyl3-methoxy xanthone and mangostinone (Asai et al. 1982). Xanthone nucleus with IUPAC numbers of carbons and chemical structure of the most studied xanthones. 1980a).-trihydroxy-4-methyl xanthone (Gopalakrishnan and Balaganesan. 2002). macluraxanthone and 1.3. 1996). BR-xanthone A and BR-xanthone B (Balasubramanian and Rajagopalan.. B. 1. caloxanthone A. 1-isomangostin hydrate.. 1986)..7-dihydroxy-3-methoxyxanthone (Matsum- oto et al.. 1987). Calabaxanthone was isolated from the bark of Calophyllum calaba and Calophyllum bracteautum in 1972 (Somanathan and Sultanbawa.7-di-isoprenyl-1.. 1997). mangostanol (Chairungsrilerd. compound 7 and mangostanine (Suksamrarn et al. it was studied by 13C MNR (Westerman et al.. tovophyllin A and B and 1. 1987. 2003). garcinone A. garcimangosones A.. Seven new xanthones were isolated from the pericarp of mangosteen-fruit in 1987: 1-isomangostin. Smeathxanthone A has also been isolated from Garcinia smeathmannii (Komguem et al.. 2000)..6H-pyrano [3. mangostenol. 1977) and later was also isolated from the pericarp of mangosteen-fruit (Mahabusarakam et al. nyl-2H. euxanthone (Gopalakrishnan et al. 3-isomangostin and 3-isomangostin hydrate (Mahabusarakam . garcinone D (Sen et al. / Food and Chemical Toxicology 46 (2008) 3227–3239 3229 Fig. 2. B and C (Sen et al. 8-hydroxycudraxanthone G. mangostenone A and B (Suksamrarn et al. 2005). 1.. 1980a). 1988). Pedraza-Chaverri et al. garcinone E (Dutta et al. 2003).2-b] xanthen-6-one (Sen et al. 2006). 1.3. C and D...7-tetrahydroxy-8-isoprenyl-9H-xanthen-9-one (Huang et al.7-dihydroxyxanthone (Iinuma et al.8-trihydroxy-4-methyl xanthone and 2..8-diisoprenyl-7-carboxy-1... 1996a).J. mangostinone and esmeatxanthone A (Jung et al.
(2003) Huang et al. (1987) Mahabusarakam et al.3. .7-dihydroxy-3-methoxyxanthone 2. (1971). c-dimethylallyl)-1. (2001) Huang et al.7-Trihydroxy-2.3 dihydroxyxanthone 2-Isoprenyl-1. (1996) Iinuma et al. (1995) Gopalakrishnan et al. (1980b. Yates and Bhat (1968) and Mahabusarakam et al.3. (1995). Govindachari et al. garcinone Cb. garcinone Eb. (2002) and Jung et al. (1996) Gopalakrishnan et al. Ho et al. mangostenone C. (1983) Chin et al. Mahabusarakam et al.7-Dihydroxy-2-isoprenyl-3-methoxyxanthone 2. Gopalakrishnan et al. (1987) Suksamrarn et al.7-dihydroxy-3 methoxyxanthone 1. (1996) Iinuma et al.6-Dihydroxy-7-methoxy-8-isoprenyl-60 . 2003) Asai et al.3. (1992) Chairungsrilerd (1996a). (2002. (2006) Sen et al. (2002.6trihydroxyxanthone 5. (1987) and Jung et al. (1997). (1980b. (2003) Suksamrarn et al. garcinone Bb. (1987) and Sen et al. (2001) Huang et al. (2001) Huang et al. (2001) Gopalakrishnan and Balaganesan (2000) Gopalakrishnan and Balaganesan (2000) Matsumoto et al. (2003) Iinuma et al. (1970). compound 7b.8-Bis(c. (2001).9-Dihydroxy-2. 2003) Sen et al. (2002.8.7-dihydroxyxanthone Euxanthone Cudraxanthone 8-hydroxycudraxanthone G Esmeatxanthone A BR-xanthone A BR-xanthone B Mangostanin Mangostenone A Mangostenone B Mangostinone Gartanin 8-Deoxygartanin Garcinone A Garcinone B Garcinone C Garcinone D Garcinone E Garcimangosone A Garcimangosone B Garcimangosone C Garcimangosone D Tovophyllin A Tovophyllin B 1. demethylcalabaxanthoneb. 2003) and Huang et al. garcinone Db. (2001) Sen et al. mangostanolb. Huang et al. (2001) Suksamrarn et al.5-dihydroxy-2-isoprenyl-3-methoxyxanthone Mangostingone [7-methoxy-2-(3. (1997) Jung et al. mangostinoneb.7-Diisoprenyl-1. 6-deoxy-7-demethylmangostanin a b References Suksamrarn et al. (2003) Govindachari et al. (2006) Balasubramanian and Rajagopalan (1988) Balasubramanian and Rajagopalan (1988) Suksamrarn et al. (1987) Mahabusarakam et al.2-b] xanthen-6-one 2-(c. 1982) Sen et al.60 -dimethylpyrano(20 . 11-hydroxy-1-isomangostin. Table 3 Xanthones isolated from Garcinia mangostana fruit Xanthone Thwaitesixanthonea. (1987) and Asai et al. (1995). mangostenone D. (2006) Jung et al.30 :3. (1996) and Huang et al. (1987) Asai et al.3. 2003) Suksamrarn et al. Huang et al. Mahabusarakam et al.2-Dihydro-1. 1982). mangostaninb. (2001) a-Mangostin b-Mangostin c-Mangostin Mangostanol Mangostenol 1-Isomangostin 1-Isomangostin hydrate 3-Isomangostin 3-Isomangostin hydrate 1. (2002.2-a]xanthen-11-one. (1971) and Huang et al. (2002. (1993) and Asai et al. (1995).8-Diisoprenyl-7-carboxy-1.2-dimethyl-8-methoxy-7-isoprenyl-2H. (1987) and Suksamrarn et al. Iinuma et al. (1980b.8-di-(3-methylbut-2-enyl) xanthone 1. Yates and Stout (1958) and Stout and Krahn (1968) Dragendorff (1930). (2003) Suksamrarn et al. (2002) Asai et al. / Food and Chemical Toxicology 46 (2008) 3227–3239 References Schmid (1855). (1987) Jefferson et al.7-trihydroxyxanthone 1.3. 1-Isomangostinb 1. mangostenone E. Suksamrarn et al. (2008) It was previously isolated from Calophylum macrocarpum and Calophylum walkeri by Ampofo and Waterman (1986). (2002. Sen et al. (1995) Huang et al. Suksamrarn et al. 2003) Mahabusarakam et al.2)xanthone (compound 7) Toxyloxanthone A (trapezifolixanthone) Calabaxanthonea Demethylcalabaxanthone Caloxanthone A Macluraxanthone 1.8-trihydroxy 4-methylxanthone 2. (2006) Sundaram et al. (2001) Jung et al. (1996) and Huang et al. (1987) Huang et al. (1987). (1995). (1980a) Mahabusarakam et al. (2001) and Suksamrarn et al. 2003) Mahabusarakam et al. mangostana pericarp Xanthone J. (2001) Jung et al. (2001) Dutta et al.7-Tetrahydroxy-8-(3 methyl-2-buthenyl)-9H-xanthon-9-one a This xanthone was originally isolated from bark of Calophyllum calaba and Calophyllum bracteautum (Somanathan and Sultanbawa.6H-pyrano [3.6.3230 Table 2 Xanthones isolated from G. (2006) and Huang et al. Pedraza-Chaverri et al. (2002. (1997) and Huang et al. (2001) and Suksamrarn et al. Iinuma et al. Sakai et al. 1982). It was was also isolated from mangosteen-fruit pericarp (see Table 2). (2006) Mahabusarakam et al. gartaninb. (1987) and Jinsart et al. 2003) and Matsumoto et al. (2001) and Chairungsrilerd (1996a) Mahabusarakam et al. (2001) and Mahabusarakam et al. 1972). (2006) Huang et al.10-trihydroxy-2-(2-hydroxypropan-2-yl) -9-(3-Methylbut-2-enyl)furo[3. (2006) Jung et al.c-Dimethylallyl)-1. It was previously isolated from Cratoxylum cochinchinense by Sia et al.isoprenyl)-8-(3-methyl-2-oxo-3-buthenyl)-1. (1980b). (1986). (1987) Mahabusarakam et al.
8-bis-(isoprenyl)-9H-xanthen-9-one 1.8-bis(isoprenyl)-9H-xanthen-9-one 1.6-di(N.8-bis(isoprenyl)-9H-xanthen-9-one 1.7-Tetrahydroxyxanthone (Norathyriol) 1.6-Dihydroxy-2-(2-hydroxy-3-methylbut-3-enyl)-3.8-di(3-methylbut-2-enyl)xanthone and 2. demethylcalabaxanthone. gartanin. a.8 bis (c.2-dimethyl-pyrano[3.6-d-O-tetraacetylglucoside Mangostin 3. dulxanthone D.J.and b-mangostins and 9-hydroxycalabaxanthone also have been identiﬁed by UV spectra and quantiﬁed by HPLC with photodiode array detector and HPLC with time-of-ﬂight mass spectrometry system coupled with electrosplay ionization interface (Ji et al.5.3. (2000) Gopalakrishnan et al.and b-mangostin.6-Dihydroxy-3.7-dimethoxy-8-isoprenyl xanthone 1.8-Trihydroxy-3-methoxy-2-isoprenyl-xanthone a It was also isolated from mangosteen-fruit and pericarp (see Tables 2 and 3). and 8-desoxygartanin have been extracted of the fruit rind of mangosteen.6-Dihydroxy-3-(2.8-bis(isoprenyl)-9H-xanthen-9-one 5-Hydroxy-8-methoxy-9-(N.3-Dihydroxy-6-(N.3.3-Dihydroxy-6-(2-hydroxy-3-N. / Food and Chemical Toxicology 46 (2008) 3227–3239 Table 4 Xanthones isolated from bark of G.6-di(2.3-dihydroxypropoxy)-7-methoxy-2. c-mangostin. gartanin.6 di-O-glucoside 1-Hydroxy-3.3-Dihydroxy-2-(2-hydroxy-3-methylbut-3-enyl)-6.6.8-bis(isoprenyl)-9H-xanthen-9-one 1. b-mangostin.6-b]xanthen-9-one 2.8-bis(isoprenyl)-9H-xanthen-9-one 1.2-dimethyl-pyrano[3. Recently. gartanin.8-bis(isoprenyl).3. (2005) Ee et al.N-dimethylaminopropoxy)-7-(isoprenyl)-2.3-Dihydroxy-6-(N.2-dimethyl-pirano[3..6-Dihydroxy-8-methoxy-5-(3-methylbut-2-enyl)-xanthone (mangosharin) Garciniafuran. 1988) 1. Table 6 Synthetic derivatives of a-mangostin Derivative 3-O-methylmangostin 3. 3isomangostin.5-Trihydroxy-13.N-dimethylaminopropoxy)-7-methoxy-2. 9-hydroxycalabaxanthone.9H-xanton-9-one 1.6-di(2-hydroxy-3-N-isopropylaminopropoxy)-7-methoxy-2.7-dimethoxy-8-isoprenyl-xanthone 1-Hydroxy-3.8-bis(isoprenyl)-9H-xanthen-9-one 1.6-Dihydroxy-3.7-trimethoxy-2-isoprenyl-xanthone 1. 3.6-Dihydroxy-8-(2-hydroxy-3-methylbut-3-enyl)-3. identiﬁed and quantitatively determined used high performance liquid chromatograpy (HPLC) (Walker.2-dimethyl-pyranol[3. They also obtained several xanthones already isolated (mangostin.3.6.7-trimethoxy-2-(2-hydroxy-3-methylbut-3-enyl)-8-isoprenyl-xanthone 1-Hydroxy-3.8-bis(isoprenyl)-9H-xanthen-9-one 1-Hydroxy-3. mangostana Xanthone 1.2-b]xanthen-6-one Bicyclomangostin Di-O-methylamangostin Di-O-ethylmangostin Di-O-butylmangostin Di-O-isopropylmangostin Di-O-all Di-O-methallylmangostin ylmangostin Di-O-acethylmangostin 3-Isomangostin References Sundaram et al. (2006) Nilar and Harrison (2002) It was also isolated from mangostan-fruit and pericarp (see Tables 2 and 3).3-Dihydroxy-6(2-hydroxy-3-N-isopropylaminopropoxy)-7-methoxy-2.6. 1987).7-trihydroxy-2-methoxyxanthone 1.3-Dihydroxy-6-(4-cianopropoxi)-7-methoxy-2.7-trimethoxy-2-isoprenyl-xanthone a 3231 References Holloway and Scheinmann (1975) Nilar et al.6.N-dimethylaminopropoxy). and calabaxanthone).8-bis(isoprenyl)-9H-xanthen-9-one 1-Hydroxy-3.N-dimethylaminopropoxy)-7-(isoprenyl)-2.c-dimethylallyl)-1.7-trimethoxy-2.7-trimethoxy-2-isoprenyl-xanthone (16E)-1-hydroxy-8-(3-hydroxy-3-methylbut-1-enyl)-3.N-diethylaminoethoxy)-7-methoxy-2.3-Dihydroxy-6-(N. a.8-bis(isoprenyl)-9H-xanthen-9-one 1-Hydroxy-3.c-dimethylallyl)-1..6.2-b]xanthen-6-one 5-Hydroxy-8-methoxy-9-(2-hydroxy-3-N.2-b]xanton-6-one 5-Hydroxy-8-methoxy-9-(2-hydroxy-3-N-isopropilaminopropoxi)-7-(isoprenyl)-2. 2-(c. (1979) Mahabusarakam et al.8-bis(isoprenyl)-9H-xanthen-9-one 1.6-di(4-cianopropoxy)-7-methoxy-2.3-Dihydroxy-6-acetoxy-7-ethoxy-2. Pedraza-Chaverri et al.6. 6-O-Methylmangostanin. 8-desoxygartanin.13-dimethyl-2H-piran[7.7-Tetrahydroxy-O-glucosylxanthone Mangoxanthone. et al.6-dihydroxy-8-(3-hydroxy-3-methylbut-1-enyl)-3.8-bis(isoprenyl)-9H-xanthen-9-one 1-Hydroxy-3.3-dihydroxypropoxy)-7-methoxy-2.N-dimethylaminoethoxy)-7-(isoprenyl)-2. The xanthones 3-isomangostin. 1.7-trihydroxy-2.7-trihydroxyxanthone were isolated of the arils (seed coats).7-dimethoxy-2-isoprenyl-xanthone 1.7-methoxy-2.7-dimethoxy-2-isoprenyl-8-(2-oxo-3-methylbut-3-enyl)-xanthone (16E)-1.6.2-b]xanthen-6-one 5-Hydroxy-8-methoxy-9-(3-N.6-Dihydroxy-3-methoxy-2-isoprenyl xanthone Gartanina 1. mangostanina. 2007).N-diethylaminoetoxi)-7-methoxy-2. (1983) Shankaranarayan et al. 1.N-dimethylaminoethoxy)-7-methoxy-2. Table 5 Xanthones isolated from mangosteen leaves (Parveen and Khan. (1997) . 2007).7-trimethoxy-2-isoprenyl-8-(2-oxo-3-methylbut-3-enyl)-xanthone 1-Hydroxy-3.6. 1.7-dihydroxy-3-methoxyxanthone.6-di-O-methylmangostin Mangostin triacetate Mangostin 3.7-dimethoxy-2-isoprenylxanthone 1.3.2-dimethyl-pyrano[3.6.7-dimethoxy-2-isoprenyl-xanthone 1-Hydroxy-2-(2-hydroxy-3-methylbut-3-enyl)-3.7-trimethoxy-8-isoprenyl-xanthone 1-Hydroxy-8-(2-hydroxy-3-methylbut-3-enyl)-3.2-b]xanthen-6-one 5-Hydroxy-8-methyl-(3-cyanobutoxy)-7-(isoprenyl)-2.
D and E (Suksamrarn et al. Nilar and Harrison. 2000).55 and 112. 2007). Moongkarndi et al. Garcia et al.. 2007. 10.8. (2005) Jung et al.76 ± 1. 21 xanthones have been isolated from trunk and branches of GML (Holloway and Scheinmann. a and cmangostins showed antioxidant activity using the ferric thiocyanate method (Yoshikawa et al. (2006) studied the antioxidant and neuroprotective properties of four extracts obtained from mangosteenfruit pericarp (water. Weecharangsan et al.66 lg/mL. (2000) also found that a-mangostin and their synthetic derivatives prevent the decrease of the a-tocopherol consumption induced by LDL oxidation. Chin et al. respectively. and (iii) decreases the a-tocopherol consumption induced by LDL oxidation. Eupatorium odoratum and Senna alata (IC50 of 32. propanediol or nitrile reduced the antioxidant activity (Mahabusarakam et al. both extracts exhibited neuroprotective activity when they used concentration of 50 lg/mL. 1-hydroxy-6-acetoxy-3-methoxy-2-isoprenylxanthone and gartanin were isolated from mangosteen leaves (Parveen and Khan. Haruenkit et al. 2002. In total. Consistently.1. odoratum. branches. On the other hand.2-a]xanthen-11-one and 6-deoxy-7demethylmangostanin. (1994) found that the methanolic extracts of GML hulls showed DPPH radical scavenging activity.8% of superoxide anion (OÅ2À ) inhibition ratio (62.3232 Table 7 Antioxidant properties of G. The antioxidant capacity of these extracts was tested on a neuroblastoma cell line (NG108-15) exposed to hydrogen peroxide (H2O2). and the 2. 95% ethanol and ethyl acetate).2-dihydro-1. (1995) Fan and Su (1997) Mahabusarakam et al. 2005. 1988) (Table 5). They found that a-mangostin (i) prolonged lag time of conjugated dienes at 234 nm in a dose-dependent manner. mangostana G.. (2008) The methanol extract of the fruit hulls of GML showed DPPH scavenging activity a-Mangostin inhibited copper-induced LDL oxidation in vitro a and c-Mangostin showed antioxidant activity using the ferric thiocyanate method The copper-induced LDL oxidation in vitro was inhibited by a-mangostin and by prenylated xanthones derived from this xanthone Methanolic extract of the edible portion of GML exhibited antioxidant activity using DPPH and ABTS assays The crude methanol extract of pericarp from GML ameliorated the intracellular production of ROS in SKBR3 cells The pericarp extract of GML was able to scavenge HOÅ and effective to inhibit lipid peroxidation Several xanthones showed scavenging ONOOÀ ability in vitro The aqueous and ethanolic extracts of the pericarp of GML present DPPH scavenging activity and protects neuroblastoma cell line NG108-15 from H2O2 citotoxicity The ethanolic extract of GM showed antioxidant activity against DPPH radicals and reduced the ROS production of PML Mangosteen-fruit showed antioxidant activity against DPPH and ABTS radicals and prevents the decrease in antioxidant activity induced by a cholesterol supplemented diet in rats a-Mangostin showed protective effect against isoproterenol-induced oxidative damage and myocardial injury in rats c-Mangostin showed HOÅ-scavenging activity 3. Fan and Su. Leong and Shui. In addition. 1997). mangostana extracts and/or xanthone J.20-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assay (Leong and Shui. Chomnawang et al. Yoshikawa et al. 1994.. as measured by the inhibition of the formation of DPPH radicals by 50%. 2007). using the ABTS and DPPH assays.2-diphenyl1-picrylhydrazyl (DPPH) radical scavenging activity (Yoshikawa et al.6-dihydroxy-3-methoxy-2-isoprenyl-xanthone..1 and 1268. Nilar et al. Williams et al. mangostana signiﬁcantly reduced the reactive oxygen species (ROS) production of polymorphonuclear leucocytes (PML) with 77. Xanthones from whole fruit. More recently.13 lg/mL in comparison with ethanolic extracts of Houttuynia cordata. 1. the extract of G. (2004a) Garcia et al. 2002. (2007) Devi Sampath and Vijayaraghavan (2007) Chin et al. and leaves of GML Three new xanthones were isolated from the whole mangosteen-fruit: mangostenone C. (2006) Weecharangsan et al. whereas substitution with methyl. This extract displayed an IC50 of 6. in rats fed with basal diet supplemented with 1% of cholesterol plus 5% of mangosteen the increase in plasma lipids and decrease in antioxidant activity seen with cholesterol alone was prevented. They found values of 79. On the other hand.. Weecharangsan et al. The antioxidant activity of extracts and xanthones isolated from GML has been shown using the following methods: 2. acetate. 1975. 4. (ii) diminishes thiobarbituric reactive substances (TBARS) production. Mahabusarakam et al. Leong and Shui (2002) compared the total antioxidant capacity of twenty-seven fruits available in the Singapore market. E. Main biological and medicinal properties of GML 4. cordata. Haruenkit et al. Antioxidant properties In the Table 7 the antioxidant properties of mangosteen-fruit extracts and some xanthones that have been studied are summarized. (2004a) showed that a GML extract signiﬁcantly diminished intracellular ROS production. respectively). (2000) Leong and Shui (2002) Moongkarndi et al. Haruenkit et al. The antioxidant capacity was evaluated by the DPPH method using 1. Also. 50% ethanol. (1994) Williams et al. Chomnawang et al. which was measured using 2. Pedraza-Chaverri et al.6 lM trolox equivalents/ 100 g of fresh weight for DPPH and ABTS assays. the ferric thiocyanate method (Yoshikawa et al. alata. and they have been used to perform several studies (Table 6).. respectively).. For example. In addition. 1994. These authors found that the structural modiﬁcations of a-mangostin modify the antioxidant activity. In a similar study. 50 and 100 lg/mL of each extract. 18 xanthones have been isolated from the whole mangosteen-fruit. They showed that the GML extract had the eighth place in antioxidant efﬁciency. The 50% ethanolic extract had higher neuroprotective activity than the water extract. Fan and Su.18% for H. 2006) (Table 4). 1994.. respectively). 67. 31 synthetic derivatives have been obtained from amangostin. (2005) studied the antioxidant capacity of several fruits and vegetables from the . trunk. (2007) showed the antioxidant activity of mangosteen measured with DPPH and ABTS assays. 2002. (2008) isolated and identiﬁcated two new compounds of mangosteen powder fruit 1..7-dichloroﬂuorescein diacetate (DCFH-DA) in SKBR3 cell line..98 ± 2. (2007) showed that GML ethanolic extract possesses a signiﬁcant antioxidant activity.10-trihydroxy-2-(2-hydroxypropan-2-yl)-9(3-methylbut-2-enyl)furo[3. including mangostan. and S. 44. (2006) Chomnawang et al. In addition. (1995) found that a-mangostins decreases the human low density lipoproteins (LDL) oxidation induced by copper or peroxyl radical.6%.46 lg/mL.9% and 35. Water and ethanolic (50%) extracts showed high antioxidant capacity (inhibitory concentration at 50% (IC50) = 34. Ee et al.53. / Food and Chemical Toxicology 46 (2008) 3227–3239 References Yoshikawa et al.24 and 30.. 1997). substitution of C-3 and C-6 with aminoethyl derivatives enhanced the activity. 2006. 2006) (Table 3). (2007) Haruenkit et al.
2.. c-mangostin (8). 8-deoxygartanin. Nabandith et al. 1-isomangostin (19. phase II drug-metabolizing enzyme). 2003) cell lines have been used. was associated with apoptosis in human colon cancer DLD-1 cells a-Mangostin inhibited DMBA-induced preneoplastic lesions in a mouse mammary organ culture Mangostenone C. Therefore. 2006). Matsumoto et al. and AZ521. c-mangostin. induced by a subcutaneous injection of Table 8 Antitumoral properties of xanthones isolated from Garcinia mangostana Effect Garcinone E has a cytotoxic effect on hepatoma cells lines as well as on the gastric and lung cancer cell lines Six xanthones from the pericarp of GML showed antiproliferative activity against human leukemia HL60 cells. (2006) Nakagawa et al. glutamate oxaloacetate transaminase (GOT). DL-penicillamine was used as a positive control and its IC50 was 3. garcinone E and 2-isoprenyl1. They studied the cytotoxic effect of 6 xanthones isolated from mangosteen-fruit pericarp and found that garcinone E was the most toxic. 2002).2) and garcinone D (26). a-mangostin (12. garcinone E (14. 8hydroxycudraxanthone G (4. creatine phosphokinase (CPK). They examined cytotoxic effects 72 h after cell incubation with xanthone at 5 or 40 lM. TONG. (2007) a-Mangostin showed antitumoral activity against DLD-1 cells . The above data indicate that the antioxidant properties of extracts and some xanthones isolated from GML warrant additional studies to further examine their antioxidant properties in supplementary experimental models. (2002) Matsumoto et al. NCIHut 125. (2003) studied the effect of 6 xanthones (a. Pedraza-Chaverri et al.1 lM. garcinone E.9). 6-deoxy-7-demethylmangostanin. Antitumoral properties Several studies have been designed to examine the anticancer activities of xanthones isolated from mangosteen-fruit pericarp (Table 8). In our laboratory.3. mangostinone. Chin et al. and garcinone C showed cytotoxic effect on the three human cancer cell lines References Ho et al. using murine hepatoma cells (Hepa 1c1c7) in vivo. with the exception of lung carcinoma cell line CH27 LC-1.2-a]xanthen-11-one. b and c-mangostins. were found to induce QR activity.95 lg/mL for 1. (2006) measured the peroxynitrite (ONOOÀ) scavenging capacity of 13 xanthones by monitoring the oxidation of dihydrorhodamine 123 (DHR-123).2-dihydro-1. The histological examination of rats treated with isoproterenol showed necrotic changes in the tissue with intense inﬁltration of neutrophils. (2008) tested the same xanthones for the induction of quinone reductase (QR. b and c-mangostins were particularly effective from 10 lM.J. NB4 and U937. a-mangostin induced caspase 3-dependent apoptosis in HL60 The treatment with dietary a-mangostin inhibits cells proliferation in the colon lesions in rats injected with DMH Aqueous extract of the fruit rind GML showed antileukemic activity in four cells lines a-Mangostin induced apoptosis in human leukemia cell lines Ethanolic and methanolic extracts of GML showed antiproliferative effect on human breast cancer SKBR3 cells The antiproliferative effect of a. In addition. HEpG2 and SK-Hep-1 hepatocellular carcinoma cell lines. (2002) found that garcinone E has a potent cytotoxic effect on hepatocellular carcinoma cell lines. Hep3B. / Food and Chemical Toxicology 46 (2008) 3227–3239 3233 Philippines by measurement of lipoperoxidation (linoleic acid system) and hydroxyl radical (HOÅ) scavenging (deoxyribose method).. Devi Sampath and Vijayaraghavan (2007) evaluated the effect of a-mangostin on the antioxidant defense system and on lipid peroxidation during isoproterenol-induced myocardial infarction in rats. with the exception of a-mangostin.2 lg/mL). but it was lower (IC50 > 30 lM). respectively.2). 1. mangostinone. The IC50 (lM) value for ONOO scavenging was determined for several compounds. KATO-III and AGS gastric carcinoma cell lines. mangostenone D.7-dihydroxy-3-methoxy xanthone) isolated from mangosteenfruit pericarp on the cell growth inhibition of human leukemia cell line HL60. b-mangostin.8-di-(3-methylbut-2-enyl)xanthone and mangostanin.7-trihydroxy2. Jung et al. (2005) Jung et al.and c-mangostins. garcinone E was tested against HCC36. the a-mangostin effect was shown in other leukemia cell lines: K562. H2891 and Calu-1 lung carcinoma cell lines.6). (2006) Suksamrarn et al. This xanthone showed a protective effect against lipid peroxidation and antioxidant defense system during injury-induced myocardial infarction in rats. Hepatocellular carcinoma (Ho et al.3. They also studied the ONOOÀ scavenging capacity of cudraxanthone G. All the xanthones.. 2004a) and human leukemia (Matsumoto et al.2.. catalase (CAT) and reduced glutathione (GSH). (2008) studied the HOÅ-scavenging activity of several xanthones isolated from the fruit powder of GML. On the other hand.68 and 0. but a.10-trihydroxy2-(2-hydroxypropan-2-yl)-9-(3-methylbut-2-enyl)furo[3. glutamate pyruvate transaminase (GPT) and lipid peroxides. we found that a-mangostin (pericarp isolated).2). Later. (2003) Nabandith et al. mangosteen extract and commercial mangosteen juice. HA22T.1 and 5. Cell growth of all these leukemia cell lines was inhibited by a-mangostin at 5–10 lM. 0. are able to scavenge directly ROS and prevent neurotoxicity and ROS production induced by 3-nitropropionic acid in cultured neurons (unpublished observations and Guzman-Beltran et al. glutathione peroxidase (GPx). gartanin. Ho et al. The values for garcinone lethal dose 50% (LD50) against the cell lines studied were between 0. superoxide dismutase (SOD). garcimangosone B (15.1). demethylcalabaxanthone.4 lM. ONOOÀ is the oxidant specie À (Chiproduced by the reaction between nitric oxide (NOÅ) and OÅ2 À rino et al. Garcinone E had an antitumoral effect in the following order: SK-Hep-1 > HA22T > HEpG2 > Hep3B > HCC36.and timedependent cytotoxic effects against various cancer cell lines. In addition. submitted to publication). The most abundant compound in the extract was a-mangostin. (2004) Chiang et al. Garcinone E exhibited a very broad spectrum of dose.. Only c-mangostin from the 16 xanthones tested showed HOÅ-scavenging activity (IC50 = 0. as well as marked elevation in serum enzymes such as lactate dehydrogenase (LDH). a-mangostin. Treatments of rats with isoproterenol (150 mg/kg for 2 days) showed a signiﬁcant decrease of the antioxidant enzymes glutathione-S-transferase (GST). The concentration required to double QR induction activity (CD) values of compounds were 1. SKBR3 human breast cancer (Moongkarndi et al. gartanin (9. (2004) Moongkarndi (2004a.1). all cell lines tested were killed. garcinone D. 2. Pretreatment with a-mangostin (200 mg/kg) for 6 days prior and 2 days concurrently with isoproterenol administration signiﬁcantly attenuated these changes. and it showed the highest inhibitory activity (IC50 10 lM). NUGC-3. Chin et al.8. CH27 LC-1. 4. All xanthones showed a signiﬁcant inhibition effect. They found that the extract obtained from the mangosteen-fruit pericarp had one of the highest antioxidant activities. (2004) investigated whether the administration of a-mangostin in the diet had short-term chemopreventive effects on putative preneoplastic lesions involved in rat colon carcinogenesis. 2004b) Matsumoto et al. (2004) Matsumoto et al. mangostinone and tovophyllin A. Xanthones with the highest capacity to scavenge ONOOÀ were smeathxanthone A (2.
6-di-O-(tetra acethyl)-glucoside and mangostin-3. In another study. a-mangostin competitively inhibits [3H]mepyramine (speciﬁc antagonist of histamine H1 receptor) binding to rat aortic smooth muscle cells.12-dimethylbenz[a]anthracene (DMBA) in a mouse mammary organ culture. acacia-gum treated rats (2 mL/kg) were used.9 and 159 ± 12 lg/mL against K562 and Raji cells. 2002a. breast cancer (BC-1). Shankaranarayan et al. respectively. 1M and MT showed 66.0 lg/mL (2. 1979. (2007) evaluated a-mangostin for in vitro cytotoxicity against DLD-1 cells.53. (2006) found that a.c) and several models in vivo in rats (Shankaranarayan et al. and as negative control. which was mediated by mitochondrial dysfunctions in the early phase.64 lg/mL) by inducing apoptotic cell death. and 3. 1-isomangostin and mangostin triacetate exhibited anti-inﬂammatory activity in rats tested by the carrageenan-induced hind paw edema (M. Also. Gopalakrishnan (1980) showed that a-mangostin isolated from the rinds of the mangosteen inhibited systemic anaphylaxis. and c-mangostins and methoxy-bmangostin) in human colon cancer DLD-1 cells. respectively).44 lM). Pedraza-Chaverri et al.6%. an antagonist of the H2-histamine receptor. Nakagawa et al. They demonstrated that the number of viable cells was decreased by the treatment with mangostin 20 lM. and inhibited the primary and secondary responses of adjuvant-induced arthritis in rats. such as RBL-2H3 cells (Nakatani et al.19% and 59. with IC50 values of 2.5 lM of mangostin and 2.3234 J.92 lg/mL. a-mangostin inhibited histamine-induced contractions in a dose-dependent manner with or without cimetidine. Raji and U937 leukemia cells. They found that a-mangostin induces caspases 9 and 3 activation.. the results suggest that a-mangostin and its analogs would be candidates for preventive and therapeutic application for cancer treatment. 2006).08 lg/mL). They found that this xanthone induces apotosis in HL60 cells. Oral and intraperitoneal administration (50 mg/kg) of a-mangostin.6%. 1-isomangostin. Chiang et al. the following authors have investigated the antitumoral properties of GML: Jung et al. However. cotton pellet granuloma (M. the methanolic extract showed antioxidant activity by inhibiting the intracellular ROS production. Except for methoxy-b-mangostin. (2005) studied the antiproliferative effect of 4 prenylated xanthones (a.72 lg/mL.3.. and small cell lung cancer (NCI-H187). This methanolic extract had a signiﬁcant antiproliferation activity (ED50 = 9. 2004a). P3HR1. but not of b-mangostin. amangostin exhibited the most potent effect against BC-1 cells with an IC50 value of 0. respectively).. b (G1 arrest) and c-mangostin (S arrest). 63. a chemotherapeutic agent for colorectal adenocarcinoma. Yamakuni et al. / Food and Chemical Toxicology 46 (2008) 3227–3239 1.25 ± 0.b.6-di-O-glucoside) from amangostin to be used in pharmacologic studies as well as amangostin. Chairungsrilerd et al. (1998b) also showed that 0. They determined their antitumoral properties in preneoplastic lesions induced by 7. a-mangostin inhibited contractions mediated by the histamine H1 receptor. (1996c) demonstrated that methanolic extract of mangosteen-fruit pericarp inhibits the contractions of isolated thoracic rabbit aorta induced by histamine and serotonin. As positive control. Nakatani et al. the other three xanthones strongly inhibited cell growth at 20 lM at 72 h and their antitumor efﬁcacy was correlated with the number of hydroxyl groups. They also showed the synergistic growth suppression in the cells by the combination treatment with 2.2-dimethylhydrazine.and c-mangostins are histaminergic and serotonergic receptor blocking agents. Laphookhieo et al. b. release of ROS and cytochrome C.and c-mangostins have a cytotoxic effect against NCI-H187. with an IC50 of 61 ± 9. (2006) isolated from mangosteen-fruit pericarp three new prenylated xanthones (mangostenones C. Matsumoto et al.3% and 58. an activity that was greater than the standard drug ellipticine (IC50 = 1. Moongkarndi et al. respectively. 3.46 lg/mL).8. 1996b. Chairungsrilerd et al. (2004) investigated the antileukemic activity of hot water and juice extracts of 17 most used fruits in Taiwan in K562. Also. The anti-inﬂammatory activity of these compounds was also shown in adrenalectomised rats. dexamethazone treated rats (1 mg/kg) were used. Suksamrarn et al.5 mM of 5-hydroxytryptamine (5-HT) in the rabbit aorta without affecting the contractile responses to 30 mM of KCl. The perfusion pressure response of rat coronary artery to 5-HT2A was reduced concentration dependently by c-mangostin .03–5 lM of c-mangostin puriﬁed from the GML caused a parallel rightwards shift of the concentration/response curve for the contraction elicited by 0. a-mangostin also had a cytotoxic effect against KB cells (IC50 = 2. dysplastic foci and b-catenin accumulated crypt) induced by DMH. a-mangostin inhibited DMBA-induced preneoplastic lesions with an IC50 of 1. rabbit thoracic aorta and guinea-pig trachea (Chairungsrilerd et al. mangostin-3.3% of reduction.5 lg/mL. 2004.5 lM of 5-ﬂuorouracil (5-FU). loss of mitochondrial membrane potential. apoptosis and antioxidant activity of crude methanolic extract from mangosten-fruit pericarp was evaluated using SKBR3 human breast cancer cell line as a model. Recently. (1979) made up xanthone synthetic derivatives (3-O-methyl mangostin. 3.These results indicated that mitochondria play a pivotal role in induction of apoptosis by a-mangostin..03% of reduction.. but it was less effective against P3HR1 cells. The affected expression of cyclins cdc2 and p27 shown that cell-cycle arrest was related with the antiproliferative effect of a.. (2006) isolated from mangosteen-fruit pericarp two new xanthones (8-hydroxycudraxanthone G and mangostinone) as well as 12 known xanthones. (2004) studied the mechanism of cell death induced by a-mangostin treatment in human leukemia cell line HL60. the antiproliferation. DMH (40 mg/kg body weight once a week for 2 weeks). 4. They found that dietary administration of a-mangostin signiﬁcantly inhibited the occurrence of biomarkers for shortterm colon carcinogenesis (aberrant crypt foci.. 1996a).08 lg/ mL). respectively. They also showed that neither bcl-2 family proteins nor activation of mitogen-activated protein kinases are involved in a-mangostin-induced cell death. They suggested that a. 52.45 ± 0.63% of reduction. This extract also had a moderate activity against U937 cells. 1M and MT showed 65. Furthermore. respectively) and granuloma pouch techniques (M. 2004) (Table 9). Only the hot water extract of mangosteen-fruit pericarp exhibited a potent antileukemic activity. In another study performed by the same authors (Moongkarndi et al. In summary. Anti-inﬂammatory and antiallergy properties There is evidence about antiallergy and anti-inﬂammatory properties of GML in differerent in vitro models. 2002b) and C6 rat glioma cells (Nakatani et al. This same research group studied the effect of a-mangostin on histamine-induced contractions in rabbit thoracic aorta and guinea-pig trachea (Chairungsrilerd et al. and. Mangostenone C exhibited a cytotoxic effect against the three cell lines proved. D and E) as well as 16 known xanthones. mangostin triacetate.81% and 52.99%. In addition. (2004b) tested the antiproliferative activity of 9 Thai medicinal plants against SKBR3 human breast adenocarcinoma cell line. Matsumoto et al.6-di-O-methyl mangostin.. 3 lM of phenylephrine or histamine. immunocytoadherence in guinea pigs and rats. Apoptosis was associated with antiproliferative effect of a and c-mangostins. and gartanin was able to inhibit the NCI-H187 growth (IC50 = 1. 1M and MT showed 56. 63. The extract obtained from GML had the most potent activity with an IC50 value of 15. The cytotoxic properties of these xanthones were determined against three different human cancer cell lines: epidermoid carcinoma of mouth (KB).
(1996b) Chairungsrilerd et al. 5-HT ampliﬁed. Garcinone B (20 lM) also diminished approximately 30% of lypopolisaccharide-induced nuclear factor jB activation. (2008) Deschamps et al. However. Conversion of arachidonic acid to PGE2 was inhibited by c-mangostin. 2002a). and mangostin triacetate showed antiiﬂamatory activity in several experimental models in rats a-Mangostin. 1-isomangostin.5 lM.4 and 10. which has been used in Japan as antiallergic drug. mangostana Effect References 3235 a-Mangostin. (1996a) Chairungsilerd et al. not by blocking the release of 5-HT from the central neurone. spontaneous release of PGE2 was inhibited in a concentration-dependent manner (IC50 of about 2 lM). 45 mg/kg i. a-Mangostin showed a potent inhibition on paw oedema in mice a-Mangostin inhibits human 12-LOX Shankaranarayan et al.p.and c-mangostins signiﬁcantly inhibited lipopolysaccharide-stimulated NOÅ production and cytotoxicity to RAW 264. Recently. (2006) found that garcinone B (10 lM) reduced by 30% the increase of PGE2 release induced by A23187 in C6 rat glioma cells. These results suggest that garcinone B may be a pharmacological tool to investigate intracellular signaling pathways involved in inﬂammation. (2002b) Nakatani et al. (1998a) Chairungsrilerd et al. The RAW 264. 70% and 100%) on histamine release and prostaglandin-E2 (PGE2) synthesis. This inhibition was concentration-dependent.. This same group examined the effect of c-mangostin isolated from mangosteen-fruit pericarp on arachidonic acid cascade in C6 rat glioma cells. Deschamps et al.J. ADP-induced aggregation of rabbit platelets was inhibited by c-mangostin (IC50 = 0. (1979) Gopalakrishnan et al. / Food and Chemical Toxicology 46 (2008) 3227–3239 Table 9 Anti-inﬂammatory and antiallergy properties of G. The effects of these xanthones were probed by measuring the induction of inducible nitric oxide synthase (iNOS) and COX enzyme expressions.58 lM. has anti-inﬂammatory effects in several experimental models of inﬂammation in rats and guinea pigs a-Mangostin ameliorates the histamine-induced contraction of aorta and trachea from male guinea pigs The crude methanol extract of GM hulls blocked the histaminergic and serotonergic response in isolated rabbit aorta strips. Furthermore. whereas 70% and 100% extracts showed only weak inhibition.and c-mangostins inhibited LPS-stimulated citotoxicity. (b) inhibited LPS-induced expression of COX-2 protein and its mRNA.7 macrophages. Chen et al. c-mangostin did not signiﬁcant inhibit the paw oedema in mice. (2002b) Nakatani et al. 1998a.32 lM). b and c-mangostins) suppressed the degranulation in Ag-mediated activation of IgE . NOÅ and PGE2 production. (2002b) examined the effect of extracts from mangosteen-fruit (water and ethanol 40%.and c-mangostins were evaluated by carrageenan-induced paw edema in mice.7 cells were activated with lipopolysaccharide (1 lg/ mL) for 12 h and the treatment with a. This demonstrated that in vivo a-mangostin has more anti-inﬂammatory activity than c-mangostin. Nakatani et al.1 lM for a.7 cells. A 40% ethanol extract of GML extracts (3. (c) reduced the LPS-inducible activation of NF-kB. Yamakuni et al. Based on this information. the effect of c-mangostin on nuclear factor jB activation was also examined. while the water extract of R. Itoh et al. (2006) Chen et al. a-mangostin blocked the histaminergic response and c-mangostin blocked the serotonergic response c-Mangostin is 5HT2A receptor antagonist in vascular smooth muscles and platelets c-Mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-HT2A receptors Extracts of mangosteen hulls inhibited histamine release in RBL-2H3 cells and decreased A23187 induced PGE2 synthesis in C6 rat glioma cells c-Mangostin inhibited A2318 induced PGE2 release in C6 cells and arachidonic acid conversion to PGE2 in isolated microsomes as well as the activities of both constitutive COX-1 and inducible COX-2 c-Mangostin (a) inhibited COX-1 and -2 activity and PGE2 synthesis in C6 rat glioma cells.and c-mangostins also signiﬁcantly reduced PGE2 production in lipopolysaccharide-activated RAW 264. They found that 40% ethanol extract (100 and 300 lg/mL) inhibits the histamine release induced by IgE in RBL-2H3 cells. cmangostin is a promising 5-HT2A receptor antagonist in vascular smooth muscle.8 and 2 lM. Chairungsrilerd et al.29 lM). and (d) inhibited rat carrageenan-induced paw edema Garcinone B reduced A23187-induced PGE2 release and LPS-induced transcription of NF-kB-mediated in C6 rat glioma cells a.7 cells. which also inhibited the activities of both constitutive cyclooxygenase-1 and inducible cyclooxygenase-2 (COX-1 and COX-2. but not those of constitutive COX-1. The action of a-mangostin was more rapid than that of sulindac. (2004) studied the effect of c-mangostin on spontaneous release of prostaglandin E2 and COX-2 gene expression using C6 rat glioma cells. The amangostin and sulindac (reference compound) treatment showed a potent inhibition of paw edema at 3 h and 5 h. They found that c-mangostin has a potent inhibitory activity on A23187-induced PGE2 release.5 nM). and iNOs induction in RAW 264. i. In this work. platelets and the central nervous system (Chairungsrilerd et al. (2007) (IC50 = 0. In addition. (2007) demonstrated that a-mangostin inhibited 12-human lipoxygenase (12-LOX) with an IC50 of 0. cmangostin prevents (in a concentration-dependent manner) the lipopolysaccharide-induced expression of COX-2 protein and its mRNA.or c-mangostins (5 lg/ mL) for 24 h weakly inhibited iNOS activity in activated RAW 264. (2008) demonstrated that xanthones isolated from mangosteen (a. 10.and c-mangostins. 5-HT2 and 5-HT4 receptor antagonists and inhibited [3H]spiperone binding to cultured rat aortic myocytes (IC50 = 3. This xanthone (5 lM) also affected 5-HT-induced contraction of the guinea-pig ileum (3 lM of 5-HT3) in the presence of 5-HT1. The IgE receptor activates intracellular signal transductions resulting in the release of inﬂammatory signal mediators such as histamine and this is the primary event in several allergic responses. passive cutaneous anaphylaxis reactions in rats were signiﬁcantly inhibited by this ethanol extract. This effect was higher than aqueous extract of Rubus suavissimus. (1998b) Nakatani et al. 30 and 100 lg/mL) potently inhibited A23187 (a calcium ionophore)-induced PGE2 release in C6 rat glioma cells. The two xanthones concentration-dependently reduced the induction of iNOS. and the IC50 values were 12.p. (2008) demonstrated that a. suavissimus had no effect.08 and 4. It was found that c-mangostin suppressed the inhibitor jB kinase activity to inhibit lypopolisaccharide-induced nuclear factor jB activation and thereby decreases COX-2 induction. (2004) Yamakuni et al. (1998a) showed that c-mangostin (10–40 nmol/mouse) inhibited 5-ﬂuoro-a-methyltryptamine (5-FMT. The amount of NOÅ production at 3 to 25 lM was continously measured. The anti-inﬂammatory effects of a. After 18 h of c-mangostin treatment. respectively) (Nakatani et al.7 cells with IC50 values of 11. (1980) Chairungsrilerd et al. Nakatani et al.) induced head-twitch response in mice by blocking 5-HT2A receptors. with an IC50 of about 5 lM. respectively. respectively. The a. respectively) in a concentration-dependent manner (IC50 of about 0. In addition..b). Pedraza-Chaverri et al.
antifungal and antiviral properties of xanthones and extracts obtained from GML (Tables 10 and 11). both normal and penicillin-resistant strains.5) > 3-isomangostin (125) > gartanin (250) against normal strain. Rhizupus sp. Cunninghamella echinulata a-Mangostin. (1998) Gopalakrishnan et al. (1983) Mahabusarakam et al. The xanthones with low antituberculosis potential were mangostenol and mangostanol with MIC values of 100 lg/mL and 200 lg/mL. mangostana Effect References Sundaram et al. gypseum but exhibited no activity against C. (1983) Phongpaichit et al. P. and a and b-mangostins have a potent inhibitory activity against HIV-1 protease (proteolytic cleavage) a-mangostin. (1996) Chanarat et al. cmangostin (250) and gartanin (250). 8-deoxygartanin. (1996) studied the inhibitory effect of several xanthones. Among these. Penicillium sp. with an MIC value of 0. which have been recognized as pus-forming bacteria triggering an inﬂammation in acne. Microsporum canis. 4. 1-isomangostin and 3-isomangostin showed activity against Staphylococcus aureus both normal and penicilline-resistan strains. against the growth of methicillin-resistant S. (2007) a-Mangostin strongly inhibited S. c-mangostin. the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation) of a-mangostin was between 12. Rhizopus sp. a-mangostin exhibited high efﬁcacy.57–12. c-mangostin and gartanin showed moderate activities against Trichophyton mentagrophytes and Microsporum gypseum Ethanolic extract of GM.. Suksamrarn et al. Aspergillus ﬂavus. Sundaram et al.25 lg/mL. (1994) Iinuma et al. and b-mangostins and garcinone B exhibited the most potent inhibitory effect against Mycobacterium tuberculosis. antifungal and antiviral properties Several studies have demonstrated antibacterial. Mucor sp. B. Aspergillus niger. garcinone D. The order of the efﬁcacy deter- mined by the MIC (lg/mL) was found to be methicillin (3. They found that bacteria S. gartanin. (2005) evaluated the antibacterial activity of 19 medicinal plants from Thailand against Staphylococcus epidermidis and Propionibacterium acnes. mangostana Effect References Sundaram et al.2) > 1-isomangostin (62. GML exhibited the most potent inhibitory effect. (2003) Chomnawang et al.5) > 1-isomangostin (125) > 3-isomangostin (250). (1997) found that polysaccharides obtained from mangosteen-fruit pericarp can stimulate activity of polymorphonuclear phagocytic cells against Salmonella enteritidis. Mangostin. / Food and Chemical Toxicology 46 (2008) 3227–3239 receptors in rat basophilic leukemia RBL-2H3 cells. and c-mangostin showed antibacterial activity against MRSA Polysaccharides form the pericarp of GML enhanced the ability of phagocytic cells to kill Salmonella enteritidis in vitro a and c-mangostins and garcinone B exhibited strong inhibitory effect against Mycobacterium tuberculosis Extract of GML ihibited the growth of Propionibacterium acnes and Staphylococcus epidermidis a-Mangostin is active against vancomycin resistant Enterococci (VRE) and MRSA Ethanolic extracts of GML inhibited MRSA and S.. Pedraza-Chaverri et al. c-mangostin. isolated from mangosteen-fruit pericarp. Cryptococcus neoformans. mangostanin. (1996) and Vlietinck et al. gartanin. Six xanthones including a-mangostin. A. aureus.039 lg/mL for both bacteria. aureus ATCC25923 The herbal mouthwash containing the pericarp extract of GML may be used as an adjunct in treating oral malodor Table 11 Antifungal and antiviral properties of G. tenuis.3236 J. 1-isomangostin and 3-isomangostin isolated from GML against S. Mangostin triacetate had no activity. thypimurium.. S. the activities of mangostin. Antibacterial. garcinone D.6-di-O-methyl mangostin.5 and 50 lg/mL for bacteria and between 1 and 5 lg/mL for fungi. mentagrophytes and Microsporum gypseum were tested. and for penicillin-resistant strains a-mangostin (1. Chomnawang et al. Mucor sp. All of the components showed moderate activities against T. aeruginosa.. Klebsiella sp. and Cunninghamella echinulata were also highly susceptible to xanthones. Salmonella typhimurium and Bacillus subtilis were highly susceptible to xanthones. (1986) investigated the antimicrobial activities of mangostin. Fusarium roseum and Curvularia lunata were only moderately susceptible to them. with MIC values of 1. whereas Trichophyton mentagrophytes. and Escherichia coli were only moderately susceptible to them. P.5 lg/mL. neoformans. (1997) Suksamrarn et al. mangostenone A and tovophyllin B had an MIC value of 25 lg/mL. (1997) . albicans and C. Subillis It was showed the antibacterial activity of the a.56–12. garcinone E. and D. Chen et al.56–12. Iinuma et al. Alternaria solani. In addition. and euxanthone showed antifungal activity against F.5) > methicillin (1. (2005) Voravuthikunchai and Kitpipit (2005) Rassameemasmaung et al. BR-xanthone A.. T. (1986) a-Mangostin showed antifungal activity against Epidermdophyton ﬂoccosum. Mahabusarakam et al.9) > amangostin (15.5 lg/mL and cmangostin.6) > c-mangostin (31. (2003) studied the antituberculosis potential of prenylated xanthones obtained from mangosteen-fruit pericarp. Epidermophyton ﬂoccosum. oryzae Gopalakrishnan et al. Table 10 Antibacterial properties of G. c-mangostin. gartanin. All the data above indicate that xanthones isolated from mangosteen could be a novel target of anti-inﬂammatory and antiallergic compounds. These authors suggest that the inhibitory mechanism of degranulation by xanthones was mainly due to suppression of the SYK/PLCcs/PKC pathway. (1983) studied the antibacterial and antifungal properties of a-mangostin and four of its derivatives. (1997) demonstrated that A and B rings of xanthones are important to antifungal activity. aureus. whereas Proteus sp. aeruginosa. The order of the antibacterial and antifungal efﬁciency was as follows: a-mangostin > isomangostin > 3-O-methyl mangostin > 3. aureus (MRSA).and c-mangostins in 49 species of methicillin-resistant Staphylococcus aureus (MRSA) and the antibacterial activity of a-mangostin in 50 species of MRSA and 13 species of Enterococcus spp. whereas demethylcalabaxanthone and trapezifolixanthone had an MIC value of 12. oxysprum vasinfectum. respectively. Among them a-. (2005) Sakagami et al. Only 13 Thai medicinal plants were able to inhibit the growth of both bacteria. Alternaria solani. aureus. Chanarat et al. mentagrophytes and M. gartanin.4. gartanin and c-mangostin against Candida albicans. The minimum inhibitory concentration (MIC. About fungi. with an MIC of 6.
1996c. Pharmacol. Riscoe et al. S. Phytochemistry 27. Xanthones from Guttiferae. S. N. 6. Phytochemistry 28. Novel xanthones from Garcinia mangostana.J. a xanthone-glucoside. J. In the other hand. Several natural products have been identiﬁed because of their capacity to inhibit different stages in the replication cycle of human immunodeﬁciency virus (HIV-1). K. Jiang et al. Conclusions Following the discovery of medicinal properties in components of G. Azebaze et al. 2006. Bull... Synergy between a-mangostin and gentamicin against VRE. F. H.J..05.. Azebaze et al. This suggests possible therapeutic applications that relate to GML. 1552–1554. Nguemfo. Y. The MIC value of a-mangostin against MRSA was 8 lg/mL. plaque and papillary bleeding in sixty subjects who were diagnosed as having mild or moderate chronic gingivitis. Ohizumi. Furthermore. Grant No. T. Nkengfack.. Tosa. Acknowledgements This work was supported by Programa de Apoyo a Proyectos de Investigación e Innovación Teconológica.T. Mangostana The following medicinal properties have been described about xanthones that are isolated from sources other than GML: antimalarial (Pinto et al. Among them. (2005) found that a-mangostin had inhibitory activity against vancomycin resistant Enterococci (VRE) and MRSA with MIC values of 6. falciparum.. (2007) showed that a herbal mouthwash containing the pericarp extract of GML has some effect against volatile sulfur compounds.. A. Pharmacological properties of a-mangostin. 2003..12 and 2. 1993).. gartanin. A. partial synergy between a-mangostin and ampicillin or minocycline was also shown. . 1099–1102. Scientiﬁc Publishers.. antiulcer. an antimicrobial agent used as a positive control. Prenylated xanthone derivatives with antiplasmodial activity from Allanblackia monticola. anti-inﬂammatory.. structures of BR-xanthone-A and BR-xanthone-B.. Waterman. Asai.. acnes (Chomnawang et al. with MIC values of 0. Punica granatum and Quercus infectoria were highly efﬁcient at inhibiting bacterial growth. References Ampofo. a. These studies include both natural extracts and synthetic derivatives. Iinuma.. Meyer. Liou et al. Phytochemistry 43. Ethanolic extracts from GML. Azebaze.12 ± 0. respectively. P. Phytochemistry 25. Nozoe.. In this review.. 2005. and a-mangostin and vancomycin hydrochloride against MRSA was shown. Likhitwitayawuid et al.. Recently. K.. Medicinal properties of xanthones isolated from sources other than G. Mangostin inhibited the growth of all Enterococcus spp.6 lg/mL. (2006) found that a-mangostin exhibited an IC50 value of 17 lM against P... with MIC values of 3. respectively. Direccion General de Asunto del Personal Académico (DGAPA.and c-mangostins also had an effect against MRSA. N. Alternaria tenuis and Dreschlera oryzae). antihiperlipidemic and antiatherogenic (Muruganandan et al. Lee. Chen et al. 62. Mangostin mixture had the most potent effect against MRSA. K.H. Ohta. Histaminergic and serotonergic receptor blocking substances from the medicinal plant Garcinia mangostana. Laphookhieo et al.1 to 1.. M. Pedraza-Chaverri et al. 100 and 1000 ppm in the culture medium. A. antidiabetes. Pinto et al. Dharmaratne and Wijesinghe. 2005)... Fomum. 314. Phongpaichit et al.. Mangostanol. 2005. 2006. 1995. 2005). the same author showed that G.I.. Laphookhieo et al. Two xanthones were isolated from the ethanolic extract: a.32 lM. whereas mangiferina. Laphookhieo et al. 1998a. IN207007) from Universidad Nacional Autónoma de México (UNAM). Caius. T. mangostana ethanolic extract could signiﬁcantly reduce TNF-a production generated from peripheral blood mononuclear cells by stimulating with P.41 and 4. 1996b. S.1 lM respectively)... Chairungsrilerd.. garcinone D. Ohta.E. Pharm. BR-xanthone and euxanthone showed high inhibitory activity against the three fungi. falciparum.G. The Medicinal and Poisonous Plants of India. Planta Med. (1997) demonstrated the antifungal activity of several xanthones isolated from mangosteen-fruit pericarp and some a-mangostin-derivatives against three phytopathogenic fungi (Fusarium oxysporum vasinfectum.. a novel histamine H1 receptor antagonist. 2006. Chairungsilerd. that is the lowest concentration to kill bacteria.G. E. In addition. antitumoral (Pinto et al.2 lg/mL against P. isolated from patients in Maharaj Nakorn Chiang Mai Hospital. was 0. 2006. Voravuthikunchai and Kitpipit (2005) studied aqueous an ethanolic extracts obtained from 10 traditional Thai medicinal plants for their ability to inhibit MRSA from 35 hospitals. they used 1. 0. T. so the pericarp extract may be used as an adjunct in treating oral malodor. antiviral and antifungal (reviewed in Pinto et al.. 967– 998.25 and 12. Chairungsrilerd.. Ohta. S. G. N. anticancer (Pedro et al. which was the same value as vancomycin. b-mangostin and a-mangostin exhibited a comparable IC50 value (7 and 5.. p. 1989.B. 54. 2007).. 2617–2620. with an MIC value of 1 lg/mL. 1986. 10. xanthones have been shown to inhibit proteolytic cleavage by protease inhibition (reviewed in Vlietinck et al. Furthermore... Pepstatin A (IC50 = 76 ± 5. a-mangostin. 2005. 2004) and hepatoprotective. which exhibited an IC50 value of 5. 2006.... Nine Thai plants had activity against these bacteria. respectively.26 lg/mL. H.039 and 0. 351–356.2 to 0. India. immunomodulator. Conﬂict of interest statement The authors declare that there are no conﬂicts of interest. (2006) found that b-mangostin isolated from roots of C. T.. Valentin.. 2005. Y. (1996) showed that ethanolic extract of GML effectively inhibited HIV-1 protease.and c-mangostins. Z. / Food and Chemical Toxicology 46 (2008) 3227–3239 3237 Furthermore. c-mangostin. antibacterial (Pinto et al. Ohizumi. 527.5 nM) was used as positive control. 5. respectively. 2002).81 ± 0. Nozoe.. 1998). (1994) studied the antibacterial activity of aand c-mangostins and a mangostin mixture on 49 strains of MRSA isolated from patients in Songklanagarind Hospital.. Bennett.. Takeuchi. 471–472. Chem. Nevertheless. Penicillin G was also used as control and its MIC was >50 lg/mL.5. Balasubramanian.L. 111–113. Mahabusarakam et al. Gopalakrishnan et al. the GML minimal bactericidal concentration. 2005. Phytochemistry 39. Furukawa.A. Rajagopalan. Furukawa. 2005). K. Y.48 lg/mL. 2005. 1996a. Ohizumi... many studies have been conducted. Eur. Rassameemasmaung et al. Mahabusarakam et al.. 1999). They also studied the antibacterial activity of a-mangostin on 50 strains of MRSA and 13 strains of Enterococcus spp. 1988.4 and 0.156 lg/ mL against P. further studies need to be done in order to investigate the effects of GML extracts in humans. 2006. 943–944.5 lg/mL. with an MIC value of 1. 4.. K.. cochinchinense had an IC50 value of 7. J. Antimalarial properties Several xanthones isolated from GML have shown antimalaria activity in vitro against Plasmodium falciparum. a prenyl xanthone from Garcinia mangostana. Nozoe. Xanthones and neoﬂavonoids from two Asian species of Calophyllum. Tanaka. epidermidis.. respectively. acnes and S.. exhibited an IC50 value higher than 50 lM (Riscoe et al. A xanthone from pericarps of Garcinia mangostana. the potential beneﬁcial effect of GML in both acute and chronic disease has been discussed. M. Sakagami et al.. cardioprotective (Pinto et al.b).. mangostana. Substitution in A and C rings has been shown to modify the bioactivities of the compounds.
B... J. Polya. 357. Antimicrobial activity of xanthones from Calophyllum species. M.... Pharmacol. H. Chem. Mahabusarakam. Xanthones of Garcinia Mangostana Linn. Gassner. Taylor. B.. Gritsanapan. M. Ohguchi.. Gupta. Pongpan.. Med. Fujihara.G.J. Nozoe.R. Liu. 58. Su. Sci. Taylor. 1987.. Jefferson. 20. 91–102.. 22. M. L. a xanthone from Garcinia mangostana Linn. 2008. Aust. 88.. L. W. Tosa. K.N. Luanratana. T. Mangostana L. M.C. S. N. Acid-catalysed cyclisations of xanthones: structure of a new xanthone from Garcinia mangostana Linn. W.C.S. Takayama. Daud. Wang. K. K. Kaneshiro.D. T. K.L..... Rahmani. Likhitwitayawuid.. Pongpan. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. Bioorg..K.A. 64. D. 1999. Indian Chem. Ethnopharmacol. Naunyn-Schmiedeberg’s Arch. 280–301. J. Toxicol. has potent cytotoxic effect against the hepatocellular carcinoma cell lines.. Curr. D.3238 J.. Dutta... Cancer Prev. 62.. H. N. M.J. Pharmacological effects of xanthones as cardiovascular protective agents.Y. 1932. Wiss. Wan..C.. Mahabusarakam. Uber die Konstitution des Mangostins. K.H. Sajewicz. Shieh... Three xanthones and a benzophenone from Garcinia mangostana. 1998b. Suresh...A.. Lebensm. 68.. Y. R. Harbone. K.. / Food and Chemical Toxicology 46 (2008) 3227–3239 Huang. M.W. Ohguchi. 861–865.. In vitro evaluation of antileukemic activity of 17 commonly used fruits and vegetables in Taiwan. Liebigs. 2004a. Akao. K.. Nukoolkarn.D. Chomnawang. 2006. T. in immunopathological and inﬂammatory reactions. on two different categories of colon preneoplastic lesions induced by 1. C.. T.. Avula. Mahabusarakam.T... Chen. Gupta. J. Morioka. Kinghorn. C. Med..D. T. 350–358.. 4500–4508. Biol.J. 6900–6908. Exp. 1124–1127. Ann. F.. T. 1992. Yi. Phytochemistry 31. T. W.M... Invest.. 2006... Kobayashi. Ethnopharmacol..... Holman.H. R. Moongkarndi. Med. Ohguchi.. Won.. N. Prenilated xanthones as potential antiplasmodial substances. S. Ito. Cheng.. 26B. 123. Naturally ocurring xanthones of terrestial ﬂora.. K.. Banumathi. a xanthone derivative. JP 08231396.. Prod.W. 55... P. P. Indian J. X. Baxter. Vijayaraghavan. R. R. 45. The National Institute of Science Communication and Information Resources. Keller. Planta Med.. Z. 2005.. Med. Y. 2499–2515.. Matsumoto. F.. P... J. 54. J. J. Proudfoot. Tauﬁq-Yap. Bioorg. E. Laphookhieo. Chopra. I.. Morton. Akao..P... 2005.. Garnett. 90. 2005.. 123.N. Y. Chen.. Phongpaichit. Hasegawa. 643–659. Antimicrobial effects of Thai medicinal plants against acne-inducing bacteria..C. 15. Chairungsrilerd. K..Q.G. 474–478. 2002.E... Y. Evidencia de la participación del peroxinitrito en diversas enfermedades. M... Garcia.. G. K. A. Kuete.. Xanthones from Garcinia smeathmannii (Oliver) and their antimicrobial activity. Devi Sampath. W. c-Pyrone compounds as potential anti-cancer drugs. Haruenkit.. 1713–1717. Shankaranarayanan. Akao..C. Tane. Damas. A.. K. Kinghorn.D. . T. S. Nagumo.T.. J. Antiproliferative activity of Thai medicinal plant extracts on human breast adenocarcinoma cell line.T. Gopalakrishnan.. D. 1067–1073.. 688–693.. R. 1956.. New anticonvulsant agents.M. M. 69–75.. Murakami. 2007. M.. Sasaki. G. Sarkar. Malawska.. Ji. S.. 2008. Moongkarndi. J. Res. S.. 69.. Antiproliferation. Cytotoxic and antimalarial prenylated xanthones from Cratoxylum cochinchinense. Res. Asian Pac.. N. J.L. 46. D. E.L.. T. Iinuma. W. W... S.. Scheimann.L. Shimano. G. Med. 78–83. 1932. Clin. Iinuma. Chem. Naoe. Wiriyachtra.... Garcinia Mangostana in the treatment of amoebic dysentery. Planta Med. Nozawa. J. J. Med. Nozawa. B. Scheinmann. M. 76. 37. Croft. J. Anti-inﬂammatory activity of mangostins from Garcinia mangostana.. L. 336–339. Chin. J. V. Chem. T. Chanarat. B. N. Xanthones induce cell-cycle arrest and apoptosis in human colon cancer DLD-1 cells. Y. K. Pedraza-Chaverri et al. 2077–2082. 281–282. Trakhtenberg. Asao.K. Krungkrai.. Krungkrai. 5842–5849. 1998a. B. Sakagami.. J. P. Wilairat..J. Magpantay. T.. Chomnawang. B.. Kisara. Chin. Neungton. An investigation of antioxidant capacity of fruits in Singapore markets. P. Jung.. 72. Chiang. Gautschi. on rat basophilic leukemia RBL-2H3 cell degranulation. Itoh. F. Furukawa. G. K. Drug. C. Evaluation of the antifungal activity of natural xanthones from the fruits of Garcinia mangostana and their synthetic derivatives. Y. Prod. N. p. C.. Soc. Phytochemistry 66.. 375–377.. Iinuma.. W.. 2004. 969–973. Li. K. M.. Y. 1270–1276. H. Lin. 1996. Whitman. Ann. 5620–5628. J. Nozawa.. I. S. Connolly. Deschamps.. Inhibition of wheat embryo calcium-dependent protein kinase and other kinases by mangostin and cmangostin.N.. Orozco-Ibarra. Chanmahasathien. Phytochemical Dictionary – A Handbook of Bioactive Compounds from Plants. Mol. A.. C. 540–551. p. 2005. Koyano. Poovarodom.. Kuaha. Y.C. 2008. Thevanasem. 330–333. 2004.... Assoc. Su. Muruganandan. Pharm.T. 381–382. 97. Loh. Phadungcharoen..H.J. Chem..I.. Gopalakrishnan. M. a xanthone derivative.. Miami. O. 60. T. Shieh. Escobin.. Chai.I. T... Food Chem. 35. 482.. Ee.. T.. Mahabusarakam. Nayar. Phenolic compounds from the heartwood of Garcinia mangostana. Prod. Ternai. S. N.. Tanaka. 590. Nozawa. Luanratana.. 15... CMangostin.. Prod.R. 754–758.L. Quantitative and qualitative determination of six xanthones in Garcinia mangostana L. Govindachari. W. Taylor. T.. J. 54.. 122– 151. S. Kiattansakul. C. Y.. S.. M. a novel type of 5-hydroxytryptamine 2A receptor antagonist.. J. Tanaka.. Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin. Med. 2002. Ethnopharmacol..... 1930. Chen. Matsumoto. S149– S154. Almi. Prod. M. Kinjo. G. B. Garcinone E.C. Kaslunga.. Preferencial target is mitochondria in a-mangostininduced apoptosis in human leukemia HL60 cells.. L. Indian J. 2003. Y. 239–242.. 66. Buddhasukh. Rev. Khan.. Sturton. Komguem. B. 2005. Chem. Pharm.O. Jinsart. 18..K. N. J...N. Über das Harz von Garcinia Mangostana L. H. 1975. Biochem. Jung. Asai.. 1997... Leontowicz. J. Curr. Y.. Keller. V.. H. Tadano.D.. 25–31.. Ito. 5. mangostana Linn.M... 2006... Immunopharmacological activity of polysaccharide from the pericarb of mangosteen garcinia: phagocytic intracellular killing activities.. W. Top. H. T.. Gales. 2001.N. K. J. Toxicol.C.. Iinuma. Chen. Agr. Med. 339–342.. Chemical constituents of Garcinia mangostana. Xanthones from Garcinia mangostana (Guttiferae). Inhibitory effect of xanthones isolated from the pericarp of Garcinia Mangostana L. 2539–2543. J. Nat. H. 50. N.. S. Liebigs.. Iinuma. 12. H... W. K. J. 1997. C. Lal. M. Creative Resource Systems Inc. Cheng..L. Kosem.. 745–747. E... 2007.. by LC-PDA and LC-ESI-MS. P. Technol.. Food. P.C. Nat.C. 1980. Inhibitory effects of crude a-mangostin. Chem. Sem. Ohizumi. 1993.M. Holloway. Antioxidant Xanthones from pericarp of Garcinia mangostana (Mangosteen). Nat. Tetrahedron 27..V.C. J. 903–906.. S. Pharmacol... Ito. 66.S. 1996. O. Y. Inhuma. A. 43.. 611–636. Syers. 912–916. 304. 69–85. Ohguchi. 2-dimethylhydrazine in the rat. 2007. 496.. Muthukumaraswamy. N. Chem. Mehta.Y. M.. Two novel xanthones from Garcinia mangostana. Leong. 607–609.C. 519–524. Surassmo.. Bioorg.. Rev. Gritsanapan.. Y.. W. Thailand 12. J. 2005. Isolation of c-mangostin from Garcinia Mangostana and preparation of the natural mangostins by selective demethylation. L. Wijesinghe. 5. Iinuma. B. 401–408. 2000. T. Kobayashi. N. Antibacterial activity of xanthones from guttiferaeous plants against methicillin-resistant Staphylococcus aureus. Akao. S. 2004. Planta Med. N. USA. Pharmacol. Pharmacol. 1986.. Fruits from Warm Climates. Y. 64. Chairungsrilerd. Agric.. P.. Leontowicz. Banerji.A.K.. Food Chem... Dai. Food Chem... Johnson. Das. W. Ismail. Fitoterapia 78. Ngadjui. Matsumoto.S.. M..K. Kosem. Philipp. 2004b. Srinivasan. Nat.. J. Japanese patent No. Chirino... 13. M. G. XLVI. Characterized mechanism of a-mangostin-induced cell death: Caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miRNA-143 expression in human colorectal cancer DLD-1 cells. against methicillin-resistant Staphylococcus aureus. 12. 1987. Anal. Med.J. P. Gopalakrishnan. 5799– 5806. Joshi. Agric. 843– 846. 1999. Y. H. S. Effect of c-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5ﬂuoro-alpha-methyltryptamine-induced head-twitch responses of mice. Planta Med. Gallegos.. V.. Phytochemistry 69.. W.A.. J.. L. 2000.. Pharm.S.. J.. T.. Manfouo. Meli. Lin. p. 33. Effect of Garcinia mangostana on inﬂammation caused by Propionibacterium acnes. 1992. Y. Taylor & Francis.. W. Lontsi. H. J. R. Bioorg. Chinese Agr..N. 2007.. Antimicrobial activities of chemical constituents from G. Akao. 539–544. O. K.. Cardiovasc. Sondengam. Wiriyachitra.. J. T.L. Kobayashi. Antioxidant potential of selected Philippine vegetables and fruits. Soc.. 2005. Fan. J. 1971. Huang. Bioorg. Thai. J. Planta Med. Moss.. 3919–3926. P. S. W.. W. Yoshimi. India. Chem. Antimalarial xanthones from Garcinia cowa. Likhitwitayawuid. 101. Chiang.R... S. F. 791–794. T. Nabandith. Chantrapromma.. 2007.. Bull. Chen.A. Chem. S. S. Y... 2006. P.. Matsumoto. Antioxidative mechanism of isolated components from methanol extrac of fruit hulls of G. 2007. 855–862. Crews. L. Mandal. Chem. 1998b. D. Ohizumi. 2006. Br. Miyauchi. Y. 1997. mangosteen and sneke fruit: Experiments in vitro and in vivo... Comparative study of health properties and nutritional value of durian. J. Biomed. 1987... Rocha.J.. Active constituents against HIV-1 protease from Garcinia Mangostana. 433– 438.. B. 48.. 975–979. Kowalska. Jongsomboonkusol.L. Yang. Ho. N. a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats. Y. Ethnopharmacol.L.. 6064–6069.. Chopra.. Gorinstein. 70–72. M. S. G. Sim.. 161–166. 2004. Nozawa. Dharmaratne. 64.. N. 281– 282. Xanthones-a structural perspective. A. V. Nueva Delhi. R. Xanthones with antimalarial activity from Garcinia dulcis. Kamdem. Ohta. K. J.. 1996. 497–501. T. 1970. Phytochemistry 14. V. V.. Tanaka. Y.A.. Pedraza-Chaverri.. T. J. Glossary of Indian Medicinal Plants. Nat. Effect of mangostin. P. Xanthones with quinone reductase-inducing activity from the fruits of Garcinia mangostana (Mangosteen). K. Jiang.... Helycobacter pylori inhibitors containing xanthones from Garcinia mangostana.. Pharm.. Dragendorff. Free Radic. 23. Y. Chanarat. H.. Soc. Suzui. Ngounou. D. Effect of mangiferin on hyperglycemia and atherogenicity in streptozotocin diabetic rats.. 16. Y. 2517–2518. N. H. Chem.. Nukoolkarn. Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries. Sci. Shui. 3711–3713. Nazimudeen. S. antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. Kameswaran. Liou. S. J. 1998a. J. Delgado. P. Chem. N. C. Furukawa. K. S. Ruangrungsi.. Huang. Fitoterapia 75.. Fitoterapia 71. 21. 80. Cardioprotective effect of alphamangostin. Nakagawa. Balaganesan. K.
. P. Lett. Pharmacol.. Phytochemistry 66. Temsirirkkul. Subramanian.. Mazumder. Suksamrarn. Atsumi. Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana. 3770–3772. Nakatani. Phytomedicine 12. Phytochemistry 21. A xanthone from Garcinia mangostana. Shankaranarayanan.K. 80. 239.Y. S. 3725– 3730.D. Williams. Pharm. Xanthones from the green fruit hulls of Garcinia mangostana. Bull. Suksamrarn.. Sousa. S. H. J. L. J. S.M.. Harada. P... Sirikulsathean. K. Nilrat... Murakami... Phytochemistry 27. C. 394.H. 1718–1723. Extractives of Calophyllum calaba L. M.. M.. Suwannapoch. 73– 79. T. The structures of garcinones A. Amornchat. 98. Walker. Can.M.. Beilin. T. Ohizumi. Technol. Xanthones from the heartwood of Garcinia mangostana. Two xanthones from Garcinia mangostana.B. E. Chem. 1008. Pharmacodyn. Croft.. M.. Curr. Planta Med. a xanthone derivative in mangosteen. Vieira.. Parveen. Biochem.. P. Bhat. 2007. P. UK.. N.J. 1973. M. a Thai medicinal plant. Chem. Wan.. Sen. Carbon-13 N. T. Stout.. L. A. 510–512. R. 54. D. Nguyen.. Arakawa. Arch. Schmid. N. 2005. Chuaprapaisilp. Cerqueira. Somanathan.. Nat. 761–763. Y. 46. c-Mangostin inhibits inhibitor-kappaB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells. W. 2005.H. Sarkar. 2006. B and C: three new xanthones from Garcinia mangostana. Pinto. N.. 12. L.. in C6 rat glioma cells.M. Tryoxigenated naturally ocurring xanthones.. 1157–1158. F.. W. 2006.. 281–287. 2006. S. M. Ratananukul. 1747–1750. Nagem. Nakatani. M. Effects of herbal mouthwash containing the pericarp extract of Garcinia mangostana L.. 1995. Thailand. 2223–2225. Gopalakrishnan. Nagem. J. Nilar.. H. P. N. Magnet. Aimi.. 541–548.. 1968. Yoshikawa. Pinto. 1994.. W. Garcinia mangostana. Sarkar. 1980a. Commun. Gunasekera. Stout.. High resolution NMR studies of mangostin. L.. plauque and papillary bleeding index.. Riscoe. H. P.. M. Kitpipit. Rojanapanthu. J.. Chem. 2005. N. 97–109. R. L.. Tharavichitkul.. Venkatraman. 631–636.B. 3694–3696. Isolation of three new minor xanthones from Garcinia mangostana Linn. Ongsakul. Med.P. Bunchoo.T..J. Am. T. P. Free Radic. J.A. Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen... 12. Oku. K. M..R. Saralamp. Krahn. 65. Sultanbawa. Ann. Soc.. Ngawhirunpat. Bull.D. S. 66. R. Uvais. H. Inoue. Benerji.. P. 1979. Weecharangsan. 2003.. Sci. G.S.U.K. S. 12. Mazumder. Scotland. a new xanthone from Garcinia mangostane Linn. Sci. G. Phytochemistry 19. T.... Ueber das mangostin. D. 23... Chimnoi. P.. K. Planta Med. 9. M... N. 2002b.. and optimization. 3239 Shankaranarayan. Souza..H. 1137– 1141. Res. P. Yasuda. Chem.. P.J. B.. Shimura.... Majumder. Apers. Microbiol.. K. 48. 2007. Nakatani... 1465– 1506. T. Phytochemistry 60. (Guttiferae). 2539–2549. A.. Kameswaran. N. Songklanakarin J. 64. Opanasopit. Pharmacological proﬁle of mangostin and its derivatives. Banerji. Med. Sultanbawa. Chem. Wiriyachitra. Antibacterial activity of a-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics. Med. Hase. Dharmaratne. Acad. 1977. Sousa... Tetrahedron 36. M. 2447–2479. N. V. Chem. Aroonlerk. The structure of garcinome E. Phytochemistry 55. Yakugaku Zasshi 114. Periodontol. Xanthone derivatives: new insights in biological activities. 257–269. Pharm. Aoki... 958–960. 2000. Mol. 1993.K. N. Harrison. J. Yates.. Thanuhiranlert.. Gritsanapan.. M. Pract. Sotanaphun.. Chimnoi.. Hirunrat. 2002. S.. Sen. Department of Pharmaceutical Botany. Banerji. Y. A Thai Herbal.. L. 16.. Sakai.. Nascimento.C. Ohizumi. N.. T..U. 25. vol. 10.. 2003. 1691– 1700. 129–133. 83–89. Sim. Kijjoa.. J. Planta Med. Voravuthikunchai... T. 399–405. K. 2005. Perkin Trans. S. 1994. Majumder. Kelly. Banerji. C. Tetraoxygenated naturally occurring xantones. 1996. M. R. Soc.K. P. S. Nilar.. 1996.. Peres. Sim. S. M.E. Westerman.. Faculty of Pharmacy. 19–25. U.. G. M. Kazlauskas.. Suksamrarn.. Garcinone-D. Sen. Oosawa.. K..C. Med.. and Calophyllum bracteatum Thw. Komutiban. Curr.. Activity of medicinal plant extracts against hospital isolates of methicillin-resistant Staphylococcus aureus..W.P. 1995. Pedraza-Chaverri et al.. L.S. Sarkar. K.C..C. F. Organ. G. R.. 1935–1943. mode of action. 1986.L. A. 857– 859.. Bull..K.. J. H. A. Prod. W. L. Nakahata. Mangostin inhibits the oxidative modiﬁcation of human low density lipoprotein.. 1988.X. 203–208. K.. Phytochemistry 38.. p. Ther..E.. 59–60. Pedro. M. Arakawa. I. 1972. 2002.. Sundaram. Antibacterial activities of extracts from Garcinia mangostana pericarps on methicillin-resistant Staphylococcus aureus and Enterococcus species. Antimicrobial activities of Garcinia mangostana.G. Neurosci.M... Inhibition of cyclooxygenase and prostaglandin E2 syntesis by c-mangostin. Pharm. A.C.. 1229–1234. L.. P. Structure of b-mangostin. Xanthones and benzophenones from Garcinia grifﬁthii and Garcinia mangostana.. Sakagami. Pharm. N.. Part 1.... Winter. 1968.. A.. p. 51. Sarkar. Princ. Yamahara.. Si Qian. 301–305. Katsura. 1. Y.M.. 15.W. E.. Harrison. Kameswaran. Bennett. S. K.. Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia mangostana. T..... Y. Medicinal Plants in Thailand. K. 206–210. 12.m. N. Phytochemistry 44. Phongpaichit. Findhorn Press. Chem. Clayton.. 63. Pharmacol. 2002a. Khan. Med. 211– 212....K.). P.. Pinto. K. T. Harrison. Xanthones as inhibitors of growth of human cancer cell lines and their effects on the proliferation of human lymphocytes in vitro. K. J.. Shimura..J. Chem. S. Bull. A. K. A. Suttajit.. Suksamrarn... A. J.. Curr. Garcinone B reduces prostaglandin E2 release and NF-kappaB-mediated transcription in C6 rat glioma cells. M. Chem.E. Chem. Chem. Minor xanthones from the bark of Cratoxylum cochinchinense. 30. Ratananukul. H.. A.U. R. 2005.... Síntesis of xanthones: an overview.. T. Sen.J. 1980b. N.. 19B.. Chokethaworn. 11. 2004. C. Infect. The structure of mangostin. 1980. 9. Indian J... N. 1958. Antioxidant constituents from the fruit hulls of mangosteen (Garcinia mangostana L. A. Res. 2517–2538. Xanthones as antimalarial agents: discovery. M.. Takayama. Nakahata. N.J. Peres. P.. Chuakul. Uusvuori. Suksamrarn. Tsukamoto. Sep. Ohizumi.C. M. Miki. Chem.. 191–214. P. Yamakuni. Chemical investigation of Ceylonese plants.. Indian J.. Suwannapoch. 1982.. Ishiguro. Med..) originating in Vietnam. Ongsakul. Chem.. 1521–1528. Ohizumi. / Food and Chemical Toxicology 46 (2008) 3227–3239 Nakatani. Bioorg. Phakhodee. K. M.. Xanthonoids of tropical plants.. Naturally-occurring xanthones: recent developments. A..S.. Biol.. K.. 683–710. S. 1983. 25B.. G. L.. 667–674. . Yates. T.S. 24. The structure of mangostin. Lartpornmatulee. Chem. 2005.Y. 41.M. Proudfoot. Kondo. W. Curr. 297–300.A. Oosawa. N... Pierce. 2005. N. Clin. HPLC analysis of selected xanthones in mangosteen fruit. Sukma. Vlietinck.. 2413–2446.S. 1998... K.N.. Rassameemasmaung. Y. Liebigs.B. S.r stuyd of naturally occuring xanthones. M.P.. P. M. Pieters. Antioxidative and neuroprotective activities of extracts from the fruit hull of mangosteen (Garcinia mangostana Linn. Kondo. Uusvuori. Int. Plant-derived leading compounds for chemotheraphy of human immunodeﬁciency virus (HIV) infection. Sultanbawa.K. K.. Sia. V. on halitosis. Bangkok. Arakawa. M. Int. K.J.. Hase. 2002.K. Nascimento. 118. Suksamrarn. 1855. N. Siripong. 93.. M. S. L. Piyasena.. Faustino de Oliveira. Gopalakrishnan. Ratananukul. Chem. L. O.. Iinuma. Yamakuni. 175–184.