You are on page 1of 55

A study on dispersion and characterisation

of -mangostin loaded pH sensitive

microgel systems
Madihah Ahmad, Bohari M Yamin and Azwan Mat Lazim*

* Corresponding author: Azwan Mat Lazim

Author Affiliations
School of Chemical Sciences & Food Technology, Faculty Science and Technology,
Universiti Kebangsaan Malaysia, Bangi, Selangor 43600, Malaysia
For all author emails, please log on.
Chemistry Central Journal 2013, 7:85 doi:10.1186/1752-153X-7-85

The electronic version of this article is the complete one and can be found online at:

6 December 2012
13 May 2013
16 May 2013

2013 Ahmad et al.; licensee Chemistry Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is properly

-Mangostin was extracted with methanol from the rind of mangosteen fruit and purified by
using silica gel column chromatography technique. The compound is characterised using
infrared, 13C and 1H NMR as well as UVvis spectroscopy. The -mangostin dispersion in

colloidal systems was studied by incorporating it with an ionic microgel, poly (NIsopropylacrylamide)-co-2VP at different pH.
The DLS result showed the size of microgel--mangostin mixture declined from 548 nm to
200 nm upon the increment of the pH. Moreover, it was found the morphology of loaded
compound depended largely on the nature of the continuous phase of the microgel system.
Interestingly, by manipulating the pH, -mangostin tends to form crystal at extremely low pH
and transforms into spherical shapes at pH 6.
This research shows different structures of the -mangostin particle that are attributed by
adjusting the pH using microgel systems as a template.

-Mangostin; Microgel; Dynamic light scattering (DLS); Transmission electron microscope

Graphical abstract

Mangosteen, the queen of all fruits is a plant native to Southeast Asia that is used as
traditional remedy to treating skin infections wound, improve muscle and bone pain, eating
disorder, diarrhea and accelerating wound healing [1,2]. Among the essential phytonutrients
found in the rind of the mangosteen, -mangostin or 1,3,6-trihydroxy-7-methoxy, 2-8-bis (3-

methyl-but-2-enyl)-xanthen-9-one stands alone in its impressive benefits. Since it was first

discovered by W. Schmid in 1855 [3], this compound has attracted many researchers due to
its biological active properties such as antioxidant [4], anti bacteria [5], antifungal [6], anti
inflammatory [7], anti cancer [8] and anti tuberculosis [9], therapeutic drugs [10] and also
being used as mosquitoes larvicide [11]. Furthermore, it has been commercialised as
supplement in food products and natural dyes in fabric industries, which are readily available
in the worldwide market. However, its poor solubility in aqueous solution and low oral
bioavailability are the limiting factors for many applications. Therefore, it is a challenge to
the scientists to solve these problems in order to fully utilise this compound deemed suitable
for the human body systems. So far, there is only one reported study on the enhancement of
the -mangostin solubility and oral bioavailability by Aisha et al [12]. on the solid dispersion
of -mangostin in water soluble carriers using polyvinylpyrrolidone (PVP). Although this
technique showed an improvement on the dissolution of -mangostin, its commercial use is
still very limited, primarily due to manufacturing difficulties and stability problems [13]. As
an alternative, a responsive polymer has being used for -mangostin dispersions.
Much attention has been given to responsive polymers (smart polymers) due to their response
ability to external stimuli such as temperature [14], electrolyte, light and pH [15]. One of
them is microgel, a polymer colloid particle with three-dimensional network structure that
offers many applications from the viewpoint of drug delivery. It can be manipulated as
nanoreactor which controls the size property, from macrometers to nanometers [13-15].
Moreover, this polymer is responsive and having large surface network area enables to
incorporate with bio-related molecules. This smart system is used for bioactive molecules
entrapments including drugs, proteins, carbohydrates and DNA [14-16]. Its applications are
not only limited for biomedical purposes but are widely applied for the incorporation of
inorganic nanocrystals, quantum dots [16,17], magnetic nanoparticles [18,19], optical
imaging for living cells and photodynamic therapy [20].
Ionic microgels are formed when at least one of the co-monomer becomes charged
specifically when the pH reaches the pKa of that species. Generally monomer such as 2vinylpyridine [21], acrylic acid [22] and methacrylic acid [23] are used to produce a pH
responsive microgel, which can be synthesized via emulsion polymerisation or surfactant free

emulsion polymerisation [24]. Xu et al [25] reported on the utilization of poly (caprolactone)-pluronicpoly-(-caprolactone)-dimethylacrylic (PCFC-DMA) as a vitamin
B12 carrier. These modified microgels were discovered to be very sensitive towards pH. They
found the vitamin B12 could be released from the microgel faster at pH 7.4 than at pH 12.
Wang et al [26]. studied the utilization of poly (N-isopropylacrylamide-co-acrylamide) as
bleomycin drug carrier. The result showed the releasing rates of bleomycin from the microgel
exhibited diffusion control at human body temperature.
Both experiments discussed on the successful of using microgel as a carrier for commercially
bioactive molecules yet, there was no attempt of incorporating microgel with any organic
bioactive compounds. Therefore, this paper discussed on the characterisations of extracted mangostin and the attempt of its dispersion in an ionic microgel system, poly (Nisopropylacrilamide) PNIPAM with a co-monomer 2-vinylpyridine (PNIPAM-co-2VP). The
stability over a range of pH in microgel system is also reported

Results and discussion

-Mangostin characterisation
-mangostin as in Figure 1 was obtained as a yellow crystalline solid and had a melting point
of 175177C. The infrared spectrum showed the stretching of hydroxyl (OH) and carbonyl
(C=O) group at 3256 and 1639 cm-1 respectively. The band at 1460 cm-1 showed the
presence of aromatic C=C group while the band at 1077 cm-1 represents C-O ether bond. The
stretching of C-H bond at 2856, 2925 and 2962 cm-1 was consistent with the presence of
methyl groups in this compound. The infrared spectrum indicated the functional groups in the
extracted compound have a similarity to xanthone [27]. NMR (DMSO-d6, 400 MHz) H
(ppm): 1.59 (6H, s, H-14 and H-15),1.70 (6H, s, H19 and H20), 2.50 (4H, d, H11 and H16),
3.18 (3H, s, -OCH3), 5.13 (2H, d, H12), 6.33 (1H, s, H4), 6.78 (1H, s, H5), 13.69 (3H, s, C1OH,C3-OH and C6-OH). 13C NMR (DMSO-d6, 400 MHz) C (ppm): 17.97 (C-14 and C-20),
18.28 (C-15 and C-19), 25.79 (C-11 and C-16), 60.49 (OCH3), 92.54 (C-4), 102.03 (C-5 and
C9a), 109.98 (C-2), 110.19 (C-8a), 122.65(C-12), 123.86 (C-17), 130.94 (C-13 and C-18),
136.73 (C-8), 143.63 (C-7), 154.47 (C-4a), 157.20 (C-6), 158.9 (C-10a), 160.11 (C-1), 162.59
(C-3), 181.59 (C-9). The NMR data are consistent with the literature [28].

Figure 1. Infra-red spectrum and the structure of -mangostin.

The UVvis spectra of -mangostin as seen in Figure 2 showed maximum absorption peaks
at 243, 317 and 352 nm. These values are in agreement with the reported values [28].
Absorption peak at 243 nm represents the C=C chromophore with the excitation energy
* transition while the peak at 317 nm is related to C=O chromophore with excitation
energy n* transition. There is one shoulder at 265 nm indicating the C-O-C with lone
pair chromophore denoting n* transition. The existence of shoulder might be due to the
interaction of the compound with the protic solvent used. However, when -mangostin is
mixed with PNIPAM-co-2VP microgel, only peaks at 317 and 352 nm are observed while
peak at 243 nm and the shoulder disappeared. The absorbance intensity of the mixture peaks
is also decreased. This showed an interaction between -mangostin and the microgel system.

Figure 2. UVvis spectra of -mangostin (a) and mixture of PNIPAM-co2VP/-mangostin (b).

Incorporating -mangostin into PNIPAM-co-2VP dispersions
The hydrodynamic diameter of 0.1 wt% cross-linked PNIPAM-co-P2VP as native microgel
particles (without) and with additional -mangostin (with concentration of 5 x 10-5 M) as a
function of pH is shown in Figure 3. Under acidic solution conditions, the PNIPAM-co-2VP
microgel particles have a large hydrodynamic diameter, however with increasing the pH, their
diameter decreases. The largest change in hydrodynamic diameter occurs at approximately
pH 4. At low pH, the pyridine groups in the polymer framework are protonated resulting in
charged microgel particles. Consequently, it caused electrostatic repulsion between the
polymer chains and increased the osmotic pressure within the particles in the network hence
led the microgel particles to swell. As a result of the hydrophilic nature of PNIPAM-co-2VP,
swelling begins when the pH is a couple of units above the pKa value of 2VP (approximately
4) and shows a gradual swelling profile with decreasing pH. These results are consistent with
observations reported by Daly & Saunders [29] and Lazim et. al [30].. Upon adding the mangostin, the hydrodynamic diameter profile for microgels decreased nearly half of the

original size, which suggests the -mangostin has infiltrated the networks. In a significant
research reported by Lazim et. al [30], if any compounds are most likely to be adsorbed to the
surface of the microgel particles and not infiltrated into the microgel network, it would be
shown by a fully swollen in hydrodynamic diameter particularly at low pH where positively
charged microgels have maximum charge.

Figure 3. Hydrodynamic diameter of PNIPAM-co-2VP microgel particles

with -mangostin () and without -mangostin () as a function of pH measured by
In both cases, the particle size reached its optimal de-swollen state at pH 5 (Dh ~200 nm).
Any further increase in pH had no significant effect on the particle size. The exact
mechanism by which the -mangostin associates with the microgel is still unclear. However,
Bradley [31] proposed that the step involved would be the electrostatic interaction
between the negatively charged of the additional compound with the cationic groups on the
microgel network. This would act to reduce the electrostatic repulsion screening of the
charges that would otherwise exists in the network [31].
TEM imaging
The mixtures of microgels and -mangostin were characterised using the transmission
electron microscope (TEM), which allowed a direct morphology dispersion investigation in
the systems without staining the necessary process. Figure 4 shows TEM images of up taking
-mangostin into PNIPAM-co-2VP microgel systems at pH 2 and pH 6. It has been
established that the microscopic gel systems were used as promising templates to prepare
nanoparticles, composite with non-classical shapes of morphology [32,33]. It can be clearly
seen that at pH2 -mangostin showed formation of nanocrystals in PNIPAM-co-2VP
microgel systems with average sizes of 148 nm. At low pH, an initially fluid-like system
slowed down gradually due to the formation of crystalline structures, hence nucleation
occurred homogeneously throughout the systems [34]. Upon increasing the pH by adding the
NaOH, the negatively charge concentration increases and neutralization occurs. As a result,
an additional attractive force between the microgel particles is introduced [35]resulting the -

mangostin agglomerated. In comparison with acidic ambience, the size of -mangostin

particle at pH 6 is larger with an average size of 217 nm (Figure 4b).

Figure 4. TEM image of mixture -mangostin/PNIPAM-co-2VP microgel

at (a) pH2 and (b) pH6.

Yellow compound was successfully extracted from the rind of Garcinia Mangostana Linn.,
which has similarity with -mangostin characteristics and supported by data that is highly
significant with previous literature. The -mangostin dispersions in microgel systems as a
function of pH were investigated. The DLS results showed that there was an interaction in the
presence of -mangostin in PNIPAM-co-2VP microgel systems in swollen state, where the
neutralization occurred which then affected the particle sizes. On the contrary, at the
collapsed state (pH 6 and higher) there was no contribution to any significant changes to the
structure of PNIPAM-co-2VP microgels since it was only a surface interaction. Interestingly,
the extreme of pH might not only affect the colloidal dispersion but also the -mangostin
morphology. At pH 2, it resulted as crystal-like shape. However, by increasing the pH value it
turned to be agglomerated as big spherical forms. This result showed PNIPAM-co-2VP could
be potentially used as a controlled-reactor triggered by pH for -mangostin particles. Over a
variation of pH, interaction of the microgel polymers with distinct crystallographic planes or
area of the growing nuclei permits control of the size, shape and structure of the organic
compounds. Moreover, it can also be used to overcome its weakness in the aqueous solubility.
The future research for investigating the retention, release, the kinetics and its mechanism
might be useful for the application of PNIPAM-co-2VP as drug delivery agent for mangostin particles to the body system.

Material and instrumentation
All experiments utilized purified water which was milli-Q water standard (PureLab, Elga),
with resistivity of 18.2 M cm. Dialysis tubing (Fisher) with a Mw cut-off of 12,000-14,000
Daltons was used for microgel purification. For all samples, pH was measured by using a
waterproof pH meter (HI98127, pHep Hanna). For poly (N-isopropylacrylamide) co-2-

vinylpyridine (PNIPAM-co 2VP) microgel synthesis, the cross-linking monomers

divinylbenzene (DVB, Aldrich, 80%) and N, N-methylenebisacrylamide (BA, Aldrich, 99%),
were used without further purification. The initiator used for the cationic microgels was 2, 2azobis (2-methylpropionamidine) dihydrochloride (V50, Waco, 95%). Aqueous solutions of
HCl and NaOH were used to adjust pH. All chemicals and solvents used were reagent grade
and used without further purification. Infrared spectra were recorded on a Perkin Elmer GX
Spectrometer by using potassium bromide pellet. The size and morphology of the sample was
investigated by using Transmission Electron Microscope (TEM) Philips CM12 model.
UV determination
The Ultra-violet spectra were determined by Shimadzu UVvis Spectrophotometer (UV
2400PC series). The sample was dissolved in ethanol and the solution was scanned from 200
to 450 nm. Ethanol was used as the background for -mangostin sample while a mixture of
ethanol and pnipam-co-2VP microgel was used for -mangostin and microgel mixture.
NMR analysis
The 1H and 13C nuclear magnetic resonance spectra were measured with Jeol JNM-ECP 400
NMR Spectrometer. Samples were dissolved in dimethylsulfoxide (DMSO)-d6 and chemical
shifts were given in parts per million (ppm) relative to tetramethylsilane (TMS) as an internal
DLS and zeta potential characterisation
Microgel particle sizes and polydispersities index (PDI) were determined by dynamic light
scattering (DLS) using a Zetasizer Nano-S (Malvern,PA). The electrophoretic mobility (e)
for -mangostin and microgel is determined as a function of pH for dispersions at 25C. The
-mangostin e values remain negative across the entire pH range from 2 to 10, whereas the
PNIPAM-co-2VP microgel e values remain positive which are consistent with the cationic
polymer remaining with positive charge.
Extraction of -mangostin
Dried mangosteen rind samples were collected from Terengganu, Malaysia and the extraction
of -mangostin was carried out by following the normal procedure of isolating natural

products as previously reported [36]. The grinded mangosteen rind was extracted with
methanol for three weeks and then separated by column chromatography eluted with the
mixture of dichloromethane-hexane (6:4) giving a fine yellow powder.
Synthesis of PNIPAM-co-2VP microgel
The PNIPAM-co-2VP microgels were synthesized by a surfactant free polymerization
technique as previously reported [37]. Briefly, 800 ml of purified water was purged with
nitrogen for 30 minutes in a 1 L, five-neck round bottom flask fitted with a mechanical
stirrer, which operated at 150 rpm. About 0.50 g cationic initiator 2, 2-azobis (2methylpropionamidine) dihydrochloride (V50, Waco) was then added to the reaction flask
and stirred. In a beaker 200 ml of purified water (milli-Q standard) (PureLab, Elga), 3.75 g of
NIPAM and 0.55 g of BA together with 1.25 g of 2-vinylpyridine (2VP) were added together
and stirred for 15 minutes. This solution was then added to the reaction vessel with the
temperature raised to 70C. The polymerization reaction was left to proceed for 6 hours with
continuous stirring (~150 rpm). The outcome of the dispersion was filtered through glass
wool followed by extensive dialysis against milli-Q water for one week with two changes of
water per day.

Competing interest
There is no conflict of interest for all authors of this article.

Authors contributions
MA carried out the extraction, purification and characterization of the compounds as well as
conducts the dispersion study. AML carried out the synthesis of microgel and drafting the
manuscript. BMY conceived the study, participated in its design and revising the manuscript
critically for important intellectual content. All authors read and approved the final

The authors would like to thank the Faculty of Science and Technology, Universiti
Kebangsaan Malaysia for the provision of laboratory facilities and technical assistance. MA

also gratefully acknowledges the scholarship from the National Science Fellowship (NSF),
MOSTI. AML acknowledge funding from DIP 201211 and FRGS/1/2011/SG/UKM/01/25.

1. DOrazio D, Raederstorff D, Schueler G, Wang-Schmidt Y, Wolfram S: Novel use of
organic compounds.
Patent US 2009, 0221693:A1.
2. Mahabusarakam W, Wiriyachitra P, Taylor WC: Chemical constituents of garcinia
J Nat Prod 1987, 50:474-478. Publisher Full Text
3. Pedraza-Chaverri J, Crdenas-Rodrguez N, Orozco-Ibarra M, Prez-Rojas JM:
Review- medicinal properties of mangosteen (Garcinia Mangostana).
Food Chem Toxicol 2008, 46:3227-3239. PubMed Abstract | Publisher Full Text
4. Suvarnakuta P, Chaweerungrat C, Devahastin S: Effects of drying methods on assay
and antioxidant activity of xanthones in mangosteen rind.
Food Chem 2011, 1:240-247.
5. Nguyen PTM, Marquis RE: Antimicrobial actions of -mangostin against oral
Can J Microbiol 2011, 3:217-225.
6. Ruchadaporn K, Kusuma J, Niratcha C: Antifungal activity of alpha-mangostin
against Candida albicans.
J Oral Sci 2009, 51:401-406. PubMed Abstract | Publisher Full Text
7. Chen L, Ling-Ling Y, Ching-Chiung W: Anti-inflammatory activity of mangostins
from Garcinia mangostana.
Food Chem Toxicol 2008, 46:688-693. PubMed Abstract | Publisher Full Text
8. Matsumoto K, Akao Y, Ohguchi K, Ito T, Tanaka T, Iinumad M, Nozawaa Y:
Xanthones induce cell-cycle arrest and apoptosis in human colon cancer DLD-1
Bioorg Med Chem 2005, 13:6064-6069. PubMed Abstract | Publisher Full Text
9. Arunrattiyakorn P, Suksamrarn S, Suwannasai N, Kanzaki H: Microbial metabolism
of -mangostin isolated from Garcinia mangostana L.

Phytochemistry 2011, 72:730-734. PubMed Abstract | Publisher Full Text

10. Moffet A, Shah P: Pharmaceutical and therapeutic composition derived from
garcinia mangostana L.
Plant Patent US 2006, 055688:A1.
11. Lan Q, Kim M: Use of -mangostin as mosquito larvicide.
Patent US 2008, 0300300:A1.
12. Aisha AFA, Ismail Z, Abu-Salah KM, Majid AMSA: Solid dispersion of mangostin improve its aqueous solubility through self-assembly of nanomicelles.
J Pharm Sci 2011, 101:815-825. PubMed Abstract | Publisher Full Text
13. Serajuddin ATM: Solid dispersion of poorly water-soluble drugs: early promises,
subsequent problems, and recent breakthroughs.
J Pharm Sci 1999, 88:1058-1066. PubMed Abstract | Publisher Full Text
14. Lusanay G, Norvez S, Iliopoulos I: Temperature-controlled release of catechol
dye in thermosensitive phenylboronate-containing copolymers: a quantitative
Eur Polym J 2010, 46:1367-1373. Publisher Full Text
15. Yin J, Dupin D, Li J, Armes SP, Liu S: pH-induced deswelling kinetics of sterically
stabilized poly(2-vinylpyridine) microgels probed by stopped-flow light
Langmuir 2008, 24:9334-9340. PubMed Abstract | Publisher Full Text
16. Hasegawa U, Nomura SM, Kaul SC, Hirano T, Akiyoshi K: Nanogelquantum dot
hybrid nanoparticles for live cell imaging.
Biochem Biophys Res Commun 2005, 331:917-921. PubMed Abstract |
Publisher Full Text
17. Fukui T, Kobayashi H, Hasegawa U, Nagasawa T, Akiyoshi K, Ishikawa I:
Intracellular delivery of nanogel-quantum dot hybrid nanoparticles into human
periodontal ligament cells.
Drug Metab Lett 2007, 1:131-135. PubMed Abstract | Publisher Full Text
18. Gupta AK, Wells S: Surface-modified superparamagnetic nanoparticles for drug
delivery: preparation, characterization, and cytotoxicity studies.
IEEE Trans Nanobiosci 2004, 3:66-73. Publisher Full Text

19. Chatterjee J, Haik Y, Chen CJ: Size dependent magnetic properties of iron oxide
J Magn Magn Mater 2003, 257:113-118. Publisher Full Text
20. Das M, Sanson N, Fava D, Kumacheva E: Zwitterionic poly(betaine-nisopropylacrylamide) microgels:properties and applications.
Langmuir 2007, 23:196-201. PubMed Abstract | Publisher Full Text
21. Loxley A, Vincent B: Equilibrium and kinetic aspects of the pH-dependent
swelling of poly(2-vinylpyridine-co-styrene) microgels.
Colloid Polym Sci 2007, 275:1108-1114.
22. Zhang J, Xu S, Kumacheva E: Polymer microgels: reactors for semiconductor,
metal, and magnetic nanoparticles.
J Am Chem Soc 2004, 126:7908-7914. PubMed Abstract | Publisher Full Text
23. Saunders BR, Crowther HM, Vincent B: Poly[(methyl methacrylate)-co(methacrylic acid)] microgel particles: swelling control using pH, cononsolvency,
and osmotic deswelling.
Macromolecules 1997, 30:482-487. Publisher Full Text
24. Tan JPK, Goh CH, Tam KC: Comparative drug release studies of two cationic
drugs from pH-responsive nanogels.
Eur J Pharm Sci 2007, 32:340-348. PubMed Abstract | Publisher Full Text
25. Xu X, Fu S, Wang K, Jia W, Guo G, Zheng X, Dong P, Guo Q, Qian Z: Preparation
and characterization of vitamin-12 loaded biodegradable pH-sensitive microgels.
J Microencapsul 2009, 26:642-648. PubMed Abstract | Publisher Full Text
26. Wang Q, Zhao Y, Yang Y, Xu H, Yang X: Thermosensitive phase behavior and
drug release of in situ gelable poly(N-isopropylacrylamide-co-acrylamide)
Colloid Polym Sci 2007, 285:515-521. Publisher Full Text
27. Boonnak N, Karalai C, Chantrapromma S, Ponglimanont C, Fun H, Kanjana-Opas A,
Laphookhieo S: Bioactive prenylated xanthones and anthraquinones
fromCratoxylum formosum ssp. Pruniflorum.
Tetrahedron 2006, 62:8850-8859. Publisher Full Text
28. Yu L, Zhao M, Yang B, Zhao Q, Jiang Y: Phenolics from hull of Garcinia
mangostana fruit and their antioxidant activities.

Food Chem 2007, 104:176-181. Publisher Full Text

29. Daly E, Saunders BR: A study of the effect of electrolyte on the swelling and
stability of poly (N-isopropylacrylamide) microgel dispersions.
Langmuir 2000, 16:5546-5552. Publisher Full Text
30. Lazim AM, Bradley M, Eastoe J, Trickett K, Mohamed A, Rogeus SE: Recovery of
gold nanoparticles using pH-sensitive microgels.
Soft Matter 2010, 6:2050-2055. Publisher Full Text
31. Bradley M, Vincent B, Warren N, Eastoe J, Vesperinas A: Poly (vinylpyridine)
core/poly (N-isopropylacrylamide) shell microgel particles: Their
characterization and the uptake and release of an anionic surfactant.
Langmuir 2008, 24:2421-2425. PubMed Abstract | Publisher Full Text
32. Vimala K, Samba Sivudu K, Murali Mohan Y, Sreedhar B, Mohana Raju K:
Controlled silver nanoparticles synthesis in semi-hydrogel networks of
poly(acrylamide) and carbohydrates: a rational methodology for antibacterial
Carbohydr Polym 2009, 75:463-471. Publisher Full Text
33. Ballauff M, Lu Y: Smart nanoparticles: preparation, characterization and
Polymer 2007, 48:1815-1823. Publisher Full Text
34. Muluneh M, Sprakel J, Wyss HM, Mattsson J, Weitz DA: Direct visualization of pHdependent evolution of structure and dynamics in microgel suspensions.
J Phys Condens Matter 2011, 23(50):505101. PubMed Abstract | Publisher Full Text
35. Cho JK, Meng Z, Lyon LA, Breedveld V: Tunable attractive and repulsive
interactions between pH-responsive microgels.
Soft Matter 2009, 5:3599-3602. Publisher Full Text
36. Pedraza-Chaverr J, Reyes-Fermn LM, Nolasco-Amaya EG, Orozco-Ibarra M,
Medina-Campos ON, Gonzlez-Cuahutencos O, Rivero-Cruz I, Mata R: ROS
scavenging capacity and neuroprottective effect of -mangostin against 3nitropropionicacid in cerebellar granule neurons.
Exp Toxicol Pathol 2009, 61:491-501. PubMed Abstract | Publisher Full Text
37. Hall RJ, Pinkrah VT, Chowdhry BZ, Snowden MJ: Heteroaggregation studies of
mixed cationic co-polymer/anionic homopolymer microgel dispersions.

Colloids Surf A 2004, 233:25-38. Publisher Full Text

-Mangostin from Garcinia mangostana Linn: an updated review of its

pharmacological properties

Mohamed Yousif Ibrahima, , ,

Abdalbasit Adam Mariodb,

Syam Mohana, b, c, d, e,

Najihah Mohamed Hashima,

Mahmood Ameen Abdullac,

Siddig Ibrahim Abdelwahabd,

Ismail Adam Arbabe,

Landa Zeenelabdin Alia

Show more
DOI: 10.1016/j.arabjc.2014.02.011
Get rights and content
Open Access funded by King Saud University
Under a Creative Commons license

Over the past decades, various studies have highlighted the pure natural compound, mangostin as their main topic. The compounds pre-clinical and pharmacological properties
have been recognized and defined in these studies. -mangostin shows strong
pharmacological effects in in vitro and in vivo model systems by targeting a number of vital
cellular factors through various mechanisms of action. Despite its important molecular
versatility, the -mangostin still has limited clinical application. In order to optimize the
conditions of this compound as a chemotherapeutic and chemopreventive agent, for instance
in diseases such as cancer, obesity, diabetes as well as inflammatory disorders, the recent
tendency is to limit the range of its pharmacological properties. The present work reviews
recent studies on the central and potential pharmacological principles as well as the
preclinical applications of the -mangostin.


CAT, catalase;

CD, concentration required to double QR induction activity;

CNS, central nervous system;

COX, cyclooxygenase;

CPK, creatine phosphokinase;

LD50, lethal dose 50%;

DMH, 1,2-dimethylhydrazine;

GSH, reduced glutathione;

GML, Garcinia mangostana Linn;

H2O2, hydrogen peroxide;

GPx, glutathione peroxidase;

GPT, glutamate pyruvate transaminase;

GST, glutathione-S-transferase;

HIV-1, human immunodeficiency virus;

IC50, inhibitory concentration at 50%;

LDH, lactate dehydrogenase;

LDL, low density lipoprotein;

LOX, lipoxygenase;

LPS, lypopolisaccharide;

MIC, minimum inhibitory concentration;

MRSA, methicillin-resistant Staphylococcus aureus;

MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide;

NO, nitric oxide;

iNOS, inducible nitric oxide sintase;

ONOO-, superoxide anion;

PGE2, prostaglandin-E2;

PML, polymorphonuclear leucocye;

QR, quinone reductase;

ROS, reactive oxygen species;

SOD, superoxide dismutase;

TBARS, thiobarbituric reactive substances;

VRE, Vancomycin Resistant Enterococci;

HPLC/MS, high performance liquid chromatography-mass spectrometry;

LC-MS/MS, liquid chromatographymass spectrometry



Garcinia mangostana Linn;

Pharmacological properties

1. Introduction
In recent times, the focus on plant research around the world has increased; numerous
evidence has been gathered to demonstrate the enormous potential of medicinal plants. By
means of modern scientific approaches, different types of medicinal plants have been
recognized and studied. The results reveal these medicinal plants as having a promising
potential, particularly in pharmacology (Fiala et al., 1985, Tapsell et al., 2006 and Triggiani et
al., 2006).
A number of human diseases have been associated with oxidative stress; these include
diabetes, cardiovascular diseases, neurodegenerative disorders and especially carcinogenesis
(Nakabeppu et al., 2006 and Triggiani et al., 2006). As a result, a lot of interest is given
towards researching naturally occurring protective antioxidants as well as their mechanisms
of action. In accordance with this, it has been revealed that a number of plant extracts or their
secondary metabolites demonstrate powerful antioxidant activity and the ability to protect
from oxidant-induced damages (Collins, 2005, Hayatsu et al., 1988, Loo, 2003 and Triggiani
et al., 2006).Consequently, it was observed in the last decade that a lot of plant extracts have
exhibited potent cancer chemopreventive properties (Ames, 1998, Ames and Gold, 1998,
Beckman and Ames, 1998, Borek, 2004 and Cassady et al., 1990). For most of these extracts,
their effects are known to be achieved via antioxidant mechanisms that either quench reactive
oxygen species, stimulate cellular antioxidant defense systems or prevent lipid peroxidation

(Carilli and Yun, 2000 and Valko et al., 2007). Mangosteen (Garcinia mangostana) Linn is a
type of fruit that grows in the Asian region such as Malaysia, Myanmar, Thailand,
Philippines, Sri Lanka and India. Mangosteen is also referred to as the queen of fruits due
to its unique and delectable tropical taste. The fruit is dark purple or reddish in colour and
contains soft and juicy edible white pulps inside. The flavor is slight acidic and sweet and it
has a delightful smell ( Jung et al., 2006). The pericarps of this fruit have been used for many
years as traditional medicine in treating sicknesses such as trauma, skin infection, abdominal
pain, dysentery and wounds ( Peres et al., 2000). Moreover, mangosteen has been proven to
contain various secondary metabolites (e.g. prenylated and oxygenated xanthones) (
Govindachari et al., 1971 and Peres et al., 2000). In 1855, -Mangostin ( Fig. 1) was found to
among the major xanthones taken from the pericarps of the mangosteen fruit ( Schmid, 1855).
The compound is a yellowish colouring matter which can be obtained from the other parts of
the plant as well, such as the dried sap and the bark ( Dragendorff, 1930). Subsequently, the
structure of this xanthone was construed by Dragendorff ( Dragendorff, 1930) and Murakami
( Murakami, 1932). The molecular formula, type and position of the substituent groups of mangostin were then determined by Yates and Stout ( Yates and Stout, 1958). This compound
has been discovered to possess a wide range of biological activities, with anti-inflammatory,
anti-tumour, cardioprotective, antidiabetic, antibacterial, antifungal, antiparasitic, antioxidant
and anti-obesity agents. In this paper, we review the main pharmacological effects of this
pure compound.

Fig. 1.

Chemical structure of -mangostin.

Figure options

2. Extraction and isolation of -mangostin

Mangosteen pericarps collected were dried, ground and extracted separately in water and
50% ethanol. The 50% ethanol extract was freeze-dried and subsequently, the dried powder
resulting from the freeze-drying process was suspended in water that was partitioned with
ethyl acetate. Then, the ethyl acetate extract was purified by chromatography on silica gel
with the n-hexane-ethyl acetate system and recrystallized to achieve > 98% purity of the
compound (Mahabusarakam et al., 1987 and Parveen et al., 1991).

3. Main pharmacological properties of -mangostin

3.1. 1Antioxidant properties

The antioxidant properties of -mangostin which have been studied are summarized in Table
1. These antioxidant properties were demonstrated through the ferric thiocyanate method (
Fan and Su, 1997 and Yoshikawa et al., 1994). ( Williams et al., 1995) discovered that
mangostin reduces copper- or peroxyl radicals-induced oxidation of the human low density
lipoproteins (LDL). They also found that -mangostin: (i) dose-dependently prolonged the
lag time of conjugated dienes at 234 nm; (ii) decreases the production of thiobarbituric
reactive substances (TBARS); and (iii) diminishes the consumption of -tocopherol that is
induced by LDL oxidation. In fact, this consumption is also decreased by the synthetic
derivatives of -mangostin. These authors also discovered that the antioxidant activity of the
-mangostin could be modified by its structural modifications. For instance, substituting C-3
and C-6 with aminoethyl derivatives caused the antioxidant activity to be enhanced, whereas
substituting them with methyl, propanediol, acetate or nitrile resulted in a decrease of
antioxidant activity ( Mahabusarakam et al., 2000). Furthermore, the IC50 (M) value for
ONOO- scavenging on a 7,12-dimethylbenz[]anthracene-induced mouse mammary organ
culture assay for different xanthones was determined by ( Jung et al., 2006). -Mangostin is
one of the compounds that possesses the highest capacity to scavenge ONOO- with 12.2 M
as opposed to 3.1 M for the positive control of DL-penicillamine.
Table 1.
Antioxidant properties of -mangostin.
-mangostin showed antioxidant properties using the ferric
thiocyanate method

(Fan and Su,
1997 and Yoshikawa et al.,

-mangostin is acting as a free radical scavenger to protect the

(Williams et al., 1995)
LDL from oxidative damage.
Structural modification of - mangostin can inhibit the
(Mahabusarakam et al.,
oxidation of LDL.
-mangostin showed antioxidant activities using authentic and
(Jung et al., 2006)
morphosydnonimine-derived roxynitrite methods.
-mangostin has a protective effect on lipid peroxidation and
(Devi Sampath and
antioxidant tissue defense system during ISO-induced
Vijayaraghavan, 2007)
myocardial infarction in rats.
-mangostins inhibited nitric oxide (NO) from
(Chen et al., 2008)
lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.
-mangostin can be an effective cardiotoxic preventative against
(Devi Sampath and
-adrenergic catecholamine induced myocardial toxicity and
Vijayaraghavan, 2007)
associated oxidative stress.
-mangostin attenuated renal dysfunction, structural damage,
oxidative/nitrosative stress and decreased the catalase
(Prez-Rojas et al., 2009)
expression in rats .

-mangostin has the ability to scavenge several ROS and has a
neuroprotective effect against 3-NP in primary cultures of
CGNs, which is associated with its ability to ameliorate 3-NPinduced ROS production.
-mangostin protects renal tubular cells by blocking CDDPinduced apoptosis through ROS generation and p53 signaling.
-mangostin induces a protective effect in postischemic heart
associated to the prevention of oxidative stress secondary to
reperfusion injury.
Table options

(Prez-Rojas et al., 2009)
(Snchez-Prez et al., 2010)
(Buelna-Chontal et al.,

The impact of -mangostin on the antioxidant defense system as well as on lipid peroxidation
during myocardial infarction in rats induced by isoproterenol was evaluated by ( Devi
Sampath and Vijayaraghavan, 2007). Results of this evaluation revealed that there was
significant decrease of the antioxidant enzymes glutathione-S-transferase (GST), glutathione
peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione
(GSH) following the treatment with isoproterenol (150 mg/kg for 2 days). On the contrary,
there was remarkable increase in serum enzymes, including creatine phosphokinase (CPK),
lactate dehydrogenase (LDH), glutamate pyruvate transaminase (GPT), glutamate
oxaloacetate transaminase (GOT) and lipid peroxides. After being histopathologically
examined, rats treated with isoproterenol exhibited necrotic alterations in the tissue, along
with intense neutrophils infiltration. These alterations were reduced significantly by a 6-day
prior pretreatment with -mangostin (200 mg/kg) and 2 days concurrently with isoproterenol
administration. The protective effect of this xanthone against lipid peroxidation and towards
the antioxidant defense system throughout injury-induced myocardial infarction in rats was
shown. In addition, nitric oxide (NO) was also significantly inhibited from
lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, and the inhibition showed an IC50
value of 12.4 M ( Chen et al., 2008).
The wholesome effect of exogenously administered -mangostin against -adrenergic
cathecolamine-induced cardiovascular toxicity, especially with regard to membrane ATPases,
lysosomal hydrolases and inflammatory mediators TNF- and Cyclooxygenase-2 (COX-2)
expressions in albino rats was explored by ( Devi Sampath and Vijayaraghavan, 2007). The
result of a 2-day induction of rats with isoproterenol (150 mg/kg body wt, i.p.) showed
increasing serum and cardiac lysosomal hydrolases (-d-glucuronidase, -d-galactosidase, d-N-acetylglucosaminidase, acid phosphatase and cathepsin-D) activities. Moreover, in the
hearts of ISO-administered rats, the cardiac levels of sodium and calcium showed a
significant increase, along with a decrease in the level of potassium and abnormal activities
of membrane-bound phosphatases (Na+K+ ATPase, Ca2+ ATPase and Mg2+ ATPase).
Expressions of Cardiac TNF- and COX-2 that were evaluated using Western blotting
showed a significant elevation in ISO-intoxicated rats. An 8-day oral pre-co-treatment with mangostin (200 mg/kg body wt) mitigated these abnormalities significantly and restored the
levels to near normalcy as opposed to the ISO-intoxicated group of rats. The preservation of
myocardial membrane integrity as well as the extenuation of inconsistent TNF- and COX-2
expressions by -mangostin are made possible by effectively mitigating ISO-induced
oxidative stress and cellular damage. The cytoprotective role of -mangostin is proven by the
restoration of cellular normalcy.

The renoprotective effect of -mangostin on cisplatin (CDDP)-induced nephrotoxicity in rats

was evaluated by ( Prez-Rojas et al., 2009). 12.5 mg/kg/day, i.g. of -mangostin was
administered for 10 days (7 days prior to and 3 days following CDDP injection). On the 7th
day, the rats were treated with a single injection of CDDP (7.5 mg/kg, i.p.). After 3 days, the
rats were killed. Effects of -mangostin include the attenuation of renal dysfunction,
oxidative/nitrosative stress and structural damage. The compound also abated the decrease in
catalase expression and increases in mrna levels of tumour necrosis factor alpha as well as
transformed growth factor beta. In a nutshell, the attenuation in oxidative/nitrosative stress,
inflammatory and fibrotic markers as well as preservation of catalase activity are inherent in
the renoprotective effect of -mangostin on CDDP-induced nephrotoxicity.
Prez-Rojas et al., 2009 discovered the ability of -mangostin to scavenge singlet oxygen,
superoxide anion and peroxynitrite anion in a concentration-dependent manner. On the
contrary, the compound was unable to scavenge hydroxyl radicals and hydrogen peroxide. Mangostin was also able to improve the neuronal death induced by 3-nitropropionic acid (3NP) in a concentration-dependent manner. This protective effect of the -mangostin was
related to the amelioration of 3-NP-induced reactive oxygen species formation.
In a study conducted by Snchez-Prez et al., 2010 to evaluate the ability of -mangostin in
protecting proximal tubule renal epithelial cells (LLC-PK1) from cisplatin CDDP-induced
apoptotic death, cells were co-incubated with 5 M -M and 100 M CDDP for a 24-hour
period. Results revealed that the following alterations were attenuated by -mangostin:
apoptotic cell death, glutathione depletion, as well as increase in reactive oxygen species and
p53 expression induced by CDDP. The preventive effect of -mangostin on CDDP-induced
apoptotic death is attributable to the inhibition of p53 expression and ROS generation.
The protective effect of -mangostin on cardiac reperfusion damage was investigated by (
Buelna-Chontal et al., 2011). The findings indicate that -mangostin preserves the
mechanical work of the cardiac, reduces the area of infarct as well as prohibits the decrease in
cardiac ATP and phosphocreatine levels in the reperfused myocardium. This particular
protective effect of the xanthone was affiliated with the reduction of oxidative stress.
Moreover, treatment with -mangostin was found to prevent the following: reperfusion
injury-induced protein oxidation (i.e. protein carbonyl content), diminution of glutathione
content and lipid peroxidation (i.e. malondialdehyde and 4-hydroxynonenal content).

3.2. 2Anticancer and cytotoxic properties

As shown in Table 2, the anticancer and cytotoxic properties of -mangostin that is isolated
from the pericarp of the mangosteen fruit have been explored through a number of studies.
Table 2.
Anticancer & cytotoxic properties of -mangostin.
-mangostin showed complete inhibition at 10 M through the
induction of apoptosis on human leukemia cell line HL60.
Crude -mangostin has a potent chemopreventive effect in short-term
colon carcinogenesis in rats.

(Matsumoto et al.,
(Nabandith et al.,

-mangostin Induces Ca2+-ATPase-dependent apoptosis via
(Sato et al., 2004)
mitochondrial pathway in PC12 cells.
-mangostin induces cell-cycle arrest and apoptosis in human colon
(Matsumoto et al.,
cancer DLD-1 cells.
-mangostin has cytotoxic effect against breast cancer (BC-1) and
(Suksamrarn et al.,
epidermoid carcinoma of the mouth (KB) cells.
-mangostin-induced cell death: Caspase-independent apoptosis with
(Nakagawa et al.,
release of endonuclease-G from mitochondria and increased miR-143
expression in human colorectal cancer DLD-1 cells.
-mangostin suppresses Pc-3 human prostate carcinoma cell metastasis
by Inhibiting Matrix Metalloproteinase-2/9 and urokinase-plasminogen (Hung et al., 2009)
expression through the JNK signaling pathway.
-mangostin Suppresses Phorbol 12-myristate 13-acetate-induced
MMP-2/MMP-9 expressions via v3 Integrin/FAK/ERK and NF-B (Shih et al., 2010)
signaling pathway in human lung adenocarcinoma A549 cells.
-mangostin suppresses TPA-Mediated MMP-2 and MMP-9
expressions through the ERK signaling pathway in MCF-7 human
(Lee et al., 2010)
breast adenocarcinoma Cells.
-mangostin has cytotoxic properties against head and neck squamous (Kaomongkolgit et
cell carcinoma (HNSCC) cell lines.
al., 2011)
-mangostin has potential cytotoxic effect against human melanoma
(Wang et al., 2011)
SK-MEL-28 cell line.
-mangostin Inhibits the proliferation of colon cancer cells via
(Yoo et al., 2011)
catenin gene regulation in Wnt/cGMP signaling pathway.
-mangostin reduces tumor growth and lymph node metastasis in an
immunocompetent xenograft model of metastatic mammary cancer
(Shibata et al., 2011)
carrying a p53 mutation.
-mangostin induced apoptotic cell death against canine osteosarcoma (Krajarng et al.,
D-17 cells.
-mangostin showed potent effects against HCT 116 colorectal
(Aisha et al., 2012)
carcinoma in an in vitro and in vino.
Table options
In a study conducted by (Matsumoto et al., 2003), the inhibitory effects of -mangostin and 5
other xanthones on the cell growth of the human leukemia cell line HL60 were explored. The
cytotoxic effects were examined 72 hours following cell incubation with -mangostin at 5 or
40 M. -mangostin was found to be especially effective from 10 M and displayed the
highest inhibitory activity (IC50 10 M) compared to other xanthones, although they also
exhibited significant suppression effect. Afterwards, other leukemia cell lines (K562, NB4
and U937) showed the -mangostin effect as well. -mangostin inhibited the cell growth of
the abovementioned leukemic cell lines at 510 M.
The ability of -mangostin administered in the diet to exert short-term chemopreventive
effects on 1,2-dimethylhydrazine (DMH)-induced putative preneoplastic lesions in rat colon
carcinogenesis through subcutaneous injection (40 mg/kg body weight, administered once a
week for 2 weeks) was examined by ( Nabandith et al., 2004). The findings showed that
administering -mangostin in the diet could significantly inhibit the release of biomarkers for

DMH-induced short term colon carcinogenesis (such as dysplastic foci, aberrant crypt foci
and -catenin accumulated crypt).
Sato et al., 2004 conducted a study to examine the cell death effects of eight xanthones on
PC12 rat pheochromocytoma cells. It was discovered that -mangostin obtained from the
fruit hull of Garcinia mangostana L. had the most potent effect among the eight compounds,
with the EC50 value of 4 M. PC12 cells treated with -mangostin displayed typical apoptotic
DNA fragmentation and caspase-3 cleavage (equivalent to activation). The time- and
concentration-dependent manners of the apoptosis induced by -mangostin were indicated by
the flow cytometric analysis. -mangostin also exhibited features of the mitochondrial
apoptotic pathway, including mitochondrial membrane depolarization and cytochrome c
release. Moreover, -mangostin remarkably inhibited the sarco/endoplasmic reticulum Ca2+ATPase. The Ca2+-ATPase inhibitory effects and the apoptotic effects of the xanthone
derivatives showed a correlation with each other. On the contrary, -mangostin treatment
caused one of the signaling molecules of endoplasmic reticulum (ER) stress, c-Jun NH2terminal kinase (JNK/SAPK), to be activated. These findings imply that -mangostin inhibits
Ca2+ATPase to bring about apoptosis through the mitochondorial pathway.
The antiproliferative effect of -mangostin along with 3 other prenylated xanthones in DLD-1
human colon cancer cells was studied by ( Matsumoto et al., 2005). It was found that mangostin strongly suppressed cell growth at 20 and its antiproliferative efficacy was
associated with the number of hydroxyl groups. The antiproliferative effect of -mangostin
was attributable to cell-cycle arrest by affecting the cyclins, cdc2 and p27 expression.
A study conducted by Suksamrarn et al., 2006 revealed that -mangostin exerted potent effect
on breast cancer (BC-1) cells at a lower IC50 value (0.92 g/mL) compared to that of the
standard drug ellipticine (IC50 = 1.46 g/mL). The compound also exerted cytotoxic effects
against epidermoid carcinoma of the mouth (KB) cells (IC50 = 2.08 g/ml).
Nakagawa et al., 2007 evaluated -mangostin for in vitro cytotoxicity against DLD-1 human
colon cancer cells. They found that treatment with 20 M of -mangostin reduced the number
of viable cells consistently. As implied by morphological findings, the cytotoxic effect of 20
M -mangostin was discovered to be largely due to apoptosis. Although no signs of
activation of any of the caspases tested were shown through Western blotting, the results of
an apoptosis inhibition assay using caspase inhibitors and the examination of caspase activity,
the release of endonuclease-G from mitochondria with the decreased mitochondrial
membrane potential was shown. In the early phase, there was an increase in the levels of
phospho-Erk1/2 until 1 h following the beginning of treatment; the levels subsequently
decreased and then increased again in the late phase. However, the level of phospho-Akt
showed a sharp decline with the process of apoptosis following 6 h of treatment. One
interesting finding is that the level of microRNA-143, which negatively regulates Erk5 at
translation, increased gradually until 24 h after the treatment. The synergistic growth
suppression in DLD-1 cells was also examined by treating the cells with a combination of mangostin and 5-FU, a chemotherapeutic agent that is deemed as one of the most effective
against colorectal adenocarcinoma. At 2.5 M each, the co-treatment with -mangostin and
5-FU enhanced growth inhibition as opposed to solely treating the cells with 5 M of mangostin or 5 M 5-FU individually. These findings show the distinctive -mangostininduced apoptosis mechanisms and its action as an effective chemosensitizer. The researchers
found that treatment with 20 M -mangostin reduced the number of viable cells.

The antimetastatic effects of -mangostin against human prostate carcinoma cell line PC-3
was found in a study by ( Hung et al., 2009). In addition, treatment with -mangostin could
decrease the expressions of the following enzymes in a concentration-dependent manner:
matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and urokinaseplasminogen activator (u-PA). -mangostin also demonstrated an inhibitory effect against the
phosphorylation of c-Jun N-terminal kinase 1 and 2 (JNK1/2) as well as inhibited the
activation of nuclear factor kappa B (NF-B), c-Fos, and c-Jun. Furthermore, the treatment
with JNK-specific inhibitor (SP600125) could reduce MMP-2, MMP-9 and u-PA expression
in PC-3 cells. These results demonstrated the ability of -mangostin to mediate PC-3 cells
metastasis through the reduction of MMP-2, MMP-9 and u-PA expression, which is done by
suppressing the JNK1/2 signaling pathway and inhibiting NF-B and AP-1 binding activity.
(Lee et al., 2010) discovered the effectiveness of -mangostin as an antimetastatic agent
against the expressions of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix
metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in human breast
adenocarcinoma cells, MCF-7. Moreover, -mangostin inhibited the activation of
extracellular signal-regulated kinase 1 and 2 (ERK1/2) that takes place in the downregulation of TPA-induced enzyme activities, protein, and MMP-2 and MMP-9 messenger
RNA levels, as well as TPA-induced degradation of inhibitor of kappaB (IB) and the
nuclear levels of nuclear factor kappa B (NF-B), c-Fos, and c-Jun. In addition, -mangostin
treatment also resulted in a dose-dependent inhibition of the binding abilities of NF-B and
activator protein-1 (AP-1). Furthermore, MCF-7 cells treated with the specific inhibitor for
ERK (U0126) could inhibit TPA-induced MMP-2 and MMP-9 expressions as well as cell
invasion and migration. Results revealed the effectiveness of -mangostin as a novel and
effective antimetastatic agent that acts through the down-regulation of MMP-2 and MMP-9
gene expressions.
(Shih et al., 2010) investigated the anti-metastatic effect possessed by -mangostin that is
exerted on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-2
(MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in A549 human lung
adenocarcinoma cells. -mangostin was found to inhibit PMA-induced adhesion, invasion
and migration. Moreover, -mangostin could inhibit v3 integrin, focal adhesion kinase
(FAK) and extracellular signal-regulated kinase1/2 (ERK1/2) activation involved in the
down-regulation of the PMA-induced enzyme activities, protein and messenger RNA levels
of MMP-2 and MMP-9. -mangostin also strongly inhibited the degradation of inhibitor of
kappaB (IB) and the nuclear levels of nuclear factor kappa B (NF-B) induced by PMA.
It was also observed that -mangostin treatment resulted in a dose-dependent inhibition on
the binding abilities of NF-B. The effect of -mangostin is further potentiated in the
reduction of FAK or ERK1/2 phosphorylation by FAK small interfering RNA (FAK siRNA).
Finally, in a concomitant manner, MMP-2 and MMP-9 expressions were significantly downregulated through the transient transfection of ERK siRNA, with considerable inhibition of
cell invasion and migration.
(Kaomongkolgit et al., 2011) examined the apoptotic effect exerted by -mangostin in the
human head and neck squamous carcinoma cells (HNSCC) HN-22, HN-30 and HN-31. The
results showed that -mangostin had exceptional apoptotic effects on HNSCC cell lines,
which induced the down-regulation of bcl-2, while on the other hand caused an up-regulation
of bax and p53 in HN-22, HN-30 and HN-31.

In a study by (Wang et al., 2011), the cytotoxic effect of xanthone compounds (-mangostin,
-mangostin, and 8-deoxygartanin) obtained from the pericarp of mangosteen was examined
using the human melanoma SK-MEL-28 cell line. All of the tested compounds were found to
induce apoptosis; especially -mangostin which induced 59.6% early apoptosis at 7.5 g/ml,
compared to merely 1.7% in untreated cells. This apoptotic effect was due to caspase
activation and mitochondrial membrane pathways disruption as shown by a 25-fold increase
in caspase-3 activity and 9-fold decrease in mitochondrial membrane potential when
compared to untreated cells.
(Yoo et al., 2011) found that -mangostin has a potential inhibitory effect against the Wnt/bcatenin signaling pathway. -mangostin inhibited TCF/-catenin transcriptional activity and
-catenin protein expression in colon cancer cells. However, instead of being dependent on catenin phosphorylation and degradation, the inhibition -catenin resulted from it gene
regulation, as indicated by increased cGMP and cGMP-dependent kinase levels.
(Shibata et al., 2011) discovered the effect of -mangostin in reducing tumor growth and
lymp node metastasis. The study was conducted using an immunocompetent xenograft model
of mouse metastatic mammary cancer which carried a p53 mutation that induces a metastatic
spectrum similar to the one observed in human breast cancers. Prior to treatment, mammary
tumors were induced by inoculating BALB/c mice syngeneic with metastatic BJMC3879luc2
cells. Treatment with -mangostin was performed at 0, 10 and 20 mg/kg/day by means of
mini-osmotic pumps and tumors were then histopathologically examined. Furthermore, in
vitro studies were conducted to investigate the antitumor mechanisms of -mangostin. The
results showed that besides having a significantly higher in vivo survival rates compared to
controls, the 20 mg/kg/day -mangostin group also showed suppression of tumor volume and
the multiplicity of lymph node metastases. Mammary tumors of mice that were given 20
mg/kg/day demonstrated a significant increase in apoptotic levels due to increased active
caspase-3 and -9 expression. It was observed that this particular dose level also produced
other considerable effects such as decreased micro vessel density and lesser numbers of
dilated lymphatic vessels with intraluminal tumor cells in mammary carcinoma tissues.
Mitochondria-mediated apoptosis, G1-phase arrest and S-phase suppression in the cell cycle
were induced by -mangostin in vitro. Considering the vital role of the activation by Akt
phosphorylation in various oncogenic processes such as cell proliferation, anti-apoptotic cell
death, angiogenesis and metastasis, in vitro and in vivo investigations of the alterations in Akt
phosphorylation induced by -mangostin treatment were also conducted. Based on
quantitative analysis and immunochemistry, -mangostin was shown to significantly decrease
phospho-Akt-threonine 308 (Thr308) levels in mammary carcinoma cell cultures and
mammary carcinoma tissues in vivo, whereas this is not the case for serine 473 (Ser473).
(Krajarng et al., 2012) examined the antiproliferative effect of -mangostin in D-17 canine
osteosarcoma cells. According to the results, antiproliferation induced by -mangostin
showed an IC50 value of 15 g/ml. Nuclear condensation and fragmentation, normally
observed in apoptosis, was also induced by -mangostin, as revealed through Hoechst 33342
nuclear staining and nucleosomal DNA-gel electrophoresis. -mangostin was also able to
induce sub-G1 peak as demonstrated by cell-cycle analysis, as well as membrane flipping of
the phosphatidylserine and the loss of mitochondrial membrane potential in D-17 cells.
The anti-colon cancer effects (including cytotoxicity, apoptosis, anti-tumorigenicity as well as
effects on cell signaling pathways) of 81% -mangostin and 16% -mangostin xanthones
extract on HCT 116 human colorectal carcinoma cells were examined by (Aisha et al., 2012).

Investigation of the in vivo anti-colon cancer activity was also conducted on subcutaneous
tumors formed in nude mice. The xanthones extract demonstrated strong cytotoxicity through
induction of the mitochondrial apoptosis pathway, with a median inhibitory concentration of
6.51.0g/ml. In addition, the extract was found to inhibit cell migration, invasion and
clonogenicity, which are three main steps in tumor metastasis. MAPK/ERK, c-Myc/Max, and
p53 cell signalling pathways were also up-regulated. The xanthones extract also inhibited the
growth of subcutaneous tumor of HCT 116 colorectal carcinoma cells significantly when fed
to the nude mice. In summary, all of the above results indicate that -mangostin would be a
suitable candidate for preventive and therapeutic applications in cancer treatment.

3.3. 3Anti-inflammatory, anti-allergy analgesic properties

In Table 3, the anti-inflammatory and anti-allergy properties of -mangostin that have been
studied are summarized.
Table 3.
Anti-inflammatory, antiallergy and analgesic properties of -mangostin.
CNS depression (ptosis, sedation, decreased motor activity,
(Shankaranarayan et
potentiation of pentobarbital sleeping time, ether anesthesia) in mice
al., 1979)
and rats.
(Shankaranarayan et
Significant antiulcer effect in rats.
al., 1979)
Prohibition systemic anaphylaxis, immunocytoadherence in guinea
(Gopalakrishnan et al.,
pigs and rats, and inhibition the primary and secondary responses of
adjuvant-induced arthritis in rats.
(Chairungsrilerd et al.,
Histaminergic and a serotonergic receptor blocking agent.
-mangostin suppressed histamine-induced contractions in rabbit
(Chairungsrilerd et al.,
thoracic aorta and guinea- pig trachea in a dose of dependent manner. 1996)
(Deschamps et al.,
Inhibition of 12-human lipoxygenase (12-LOX).
-mangostin suppressed the degranulation in Ag-mediated activation
of IgE receptors in rat basophilic leukemia RBL-2H3 cells through (Itoh et al., 2008)
SYK/PLCs/PKC pathway.
Anti-inflammatory activity by inhibition of inducible NO synthase
and cytotoxicity to mouse leukemic monocyte macrophage cell line (Chen et al., 2008)
(RAW 264.7 cells).
Analgesic and antinociceptive activity.
(Cui et al., 2010)
- mangostin inhibits allergic mediators in bone marrow-derived
(Chae et al., 2012)
mast cell.
Table options
(Shankaranarayan et al., 1979)studied the diverse pharmacological effects of -mangostin and
its derivatives [namely 3-0-methyl mangostin, 3,6-di-O-methyl mangostin, 1-isomangostin
(IM), mangostin triacetate (MT), mangostin 3,6-di-O-(tetra acetyl) glucoside (MTG) and
mangostin-6,6-di-O-glucoside (MOG)] in experimental animals. -mangostin was found to

produce CNS depression in mice and rats; characteristics of this depression include sedation,
ptosis, decreased motor activity, potentiation of pentobarbital sleeping time and ether
anesthesia. Moreover, based on the results of carrageenin-induced hind paw edema, cotton
pellet implantation and granuloma pouch techniques, -mangostin produced prominent antiinflammatory activity in rats, via both intraperitoneal and oral routes. In fact, this antiinflammatory activity was present in bilaterally adrenalectomised rats as well. No mast cell
membrane stabilizing effect was produced by the compound, and it did not prevent the
degranulation effects of polymyxin B, diazoxide and Triton X-100 on rat peritoneal mast cells
in vitro. The prothrombin time of albino rats was also not altered. Finally, administration of
-mangostin in rats revealed considerable antiulcer activity of the compound.
The effect of -mangostin in prohibiting systemic anaphylaxis and immunocytoadherence in
guinea pigs and rats was demonstrated in a study by ( Gopalakrishnan et al., 1980). The study
also found that this compound, isolated from the rinds of the mangosteen, could also inhibit
primary and secondary responses of adjuvant-induced arthritis in rats.
(Chairungsrilerd et al., 1996) showed the ability of the methanolic extract of mangosteen-fruit
pericarp to inhibit histamine- and serotonin-induced contractions of isolated rabbit thoracic
aorta. The authors suggested that -mangostin is a histaminergic receptor blocking agent,
whereas -mangostin is a serotonergic receptor blocking agent. The same research group
evaluated the effect of -mangostin on the contractions of rabbit thoracic aorta and guineapig trachea induced by histamine. Results revealed that either with or without cimetidine (the
H2-histamine receptor antagonist), -mangostin could dose-dependently suppress
contractions induced by histamine. Contractions that are mediated by the histamine H1
receptor were also prohibited. In addition, a specific histamine H1 receptor antagonist
binding to rat aortic smooth muscle cells, [3H] mepyramine, was also suppressed
competitively by -mangostin.
(Deschamps et al., 2007) showed the ability of -mangostin to inhibit 12-human
lipoxygenase (12-LOX) at an IC50 value of 0.58 M. The intracellular signal transductions
activated by the IgE receptor caused the inflammatory signal mediators such as histamine to
be released, which is a primary event in a number of allergic responses. This information
became the basis for ( Itoh et al., 2008) to demonstrate that the degranulation in Ag-mediated
activation of IgE receptors was suppressed by -mangostin in rat basophilic leukemia RBL2H3 cells. The authors suggested that suppression of the SYK/PLCs/PKC pathway played
the main role in the inhibitory mechanism of degranulation by -mangostin.
In addition, (Chen et al., 2008) demonstrated the significant effect of -mangostin in the
inhibition of lipopolysaccharide-stimulated NO- production and cytotoxicity in mouse
leukaemic monocyte macrophage cell line (RAW 264.7 cells). At 3 to 25 M -mangostin,
the amount of NO- production was measured continuously and the IC50 value was 12.4. The
production of PGE2 in lipopolysaccharide-activated RAW 264.7 cells was also significantly
reduced by -mangostin, with IC50 value of 11.08 M. To probe the effect of this xanthone,
the induction of inducible nitric oxide synthase as well as COX enzyme expressions was
measured. -mangostin concentration was found to reduce iNOS induction in a dependent
manner. 1 g/mL lipopolysaccharide was used to activate the RAW 264.7 cells for 12 h and
iNOS activity in the activated RAW 264.7 macrophages was observed to be weakly inhibited
following a 24-h treatment with 5 g/mL -mangostin. Carrageenan-induced paw edema in
mice was used to evaluate the anti-inflammatory effect of -mangostin. Both -mangostin
and sulindac (reference compound) potently inhibited paw edema. However, -mangostin

acted more rapidly, showing potent inhibition at 3 h of treatment compared to 5 h of

treatment with sulindac.
(Cui et al., 2010) showed that 25 mg/kg intragastric (i.g.) -mangostin exhibited analgesic
effects in the hot-plate. Moreover, the results demonstrate the potent peripheral and central
antinociceptive effects exerted by -mangostin in mice.
(Chae et al., 2012) investigated the effect of -mangostin on the bone marrow-derived mast
cell (BMMC) mediated allergy mechanism induced by phorbol 12-myristate 13-acetate
(PMA) plus A23187. -mangostin was shown to inhibit the production of Interleukin (IL)-6,
prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) as well as degranulation in BMMC
induced by PMA plus A23187. Another effect of -mangostin that was observed was the
repression of cyclooxygenase (COX)-2 expression. These results reflect the potential
usefulness of -mangostin in alleviating allergic inflammatory responses mediated by the
mast cell.
The above data indicate that the anti-inflammatory, antiallergic and analgesic properties
possessed by -mangostin isolated from the mangosteen fruit make it a novel and promising

3.4. Antimicrobial properties

Table 4 shows a number of studies which have demonstrated the antibacterial, antifungal and
antiviral properties of -mangostin.
Table 4.
Antibacterial, antifungal and antiviral properties of -mangostin.
-mangostin and four of its derivatives has antibacterial effect against
S. aureus, P. aeruginosa, Salmonella typhimurium and Bacillus
subtilis ,Klebsiella sp. and Escherichia coli .
-mangostin and four of its derivatives has antibacterial effect against
Epidermophyton floccosum, Alternaria solani, Mucor sp., Rhizupus
sp. , Cunninghamella echinulata , Trichophyton mentagrophytes,
Microsporum canis, Aspergillus niger, Aspergillus flavus, Penicillium
sp., Fusarium roseum and Curvularia lunata.
-mangostin showed high efficacy against the growth of methicillinresistant S. aureus (MRSA).
-mangostins inhibits HIV-1 protease.
-mangostin-derivatives have antifungal properties against three
phytopathogenic fungi (Fusarium oxysporum vasinfectum, Alternaria
tenuis and Dreschlera oryzae).
Inhibiting role in the replication cycle of HIV virus.
Potent inhibitory effect against Mycobacterium tuberculosis
-mangostin have inhibitory activity against vancomycin resistant

(Sundaram et al.,
(Sundaram et al.,
(Iinuma et al.,
(Chen et al., 1996)
(Gopalakrishnan et
al., 1997)
(Vlietinck et al.,
(Suksamrarn et al.,
(Sakagami et al.,

Enterococci (VRE) and Methicillin-resistant Staphylococcus aureus
Antibacterial activity against Methicillin-resistant Staphylococcus
aureus (MRSA).
-mangostin has effective antifungal properties against Candida
-mangostin metabolized by two fungi, Colletotrichum gloeosporioides
(EYL131) and Neosartorya spathulata (EYR042).
Table options

(Chin and Kinghorn,
(Kaomongkolgit et
al., 2009)
(Arunrattiyakorn et
al., 2011)

A study by (Sundaram et al., 1983) on the antibacterial and antifungal properties of mangostin as well as four of its derivatives found that the following bacteria were highly
susceptible to xanthones: S. aureus, P. aeruginosa, Salmonella typhimurium and Bacillus
subtilis. Klebsiella sp., Proteus sp., Klebsiella sp. and Escherichia coli showed moderate
susceptibility. Fungi that were found to be highly susceptible to xanthones include
Epidermophyton floccosum, Alternaria solani, Mucor sp., Rhizupus sp. and Cunninghamella
echinulata, whereas those found to be moderately susceptible were Trichophyton
mentagrophytes, Microsporum canis, Aspergillus niger, Aspergillus flavus, Penicillium sp.,
Fusarium roseum and Curvularia lunata. The minimum inhibitory concentration, which is
the lowest concentration of an antimicrobial required to inhibit the visible growth of a
microorganism following overnight incubation, of -mangostin was between 12.5 and 50
g/mL and between 1 and 5 g/mL for bacteria and fungi, respectively. The following is the
order of the antibacterial and antifungal efficiency: -mangostin > isomangostin > 3-Omethyl mangostin > 3, 6-di-O-methyl mangostin. On the other hand, mangostin triacetate did
not demonstrate any activity.
(Iinuma et al., 1996a; Iinuma et al., 1996b) evaluated a few xanthones isolated from the
pericarp of mangosteen fruit for their inhibitory effect against methicillin-resistant S. aureus
(MRSA) growth. Findings showed the high efficacy of -mangostin, with MIC values
ranging between 1.57 and 12.5 g/mL.
(Chen et al., 1996 and Iinuma et al., 1996a) demonstrated the effective inhibition of HIV-1
protease by the ethanolic extract. Using Pepstatin A as a positive control at an IC50 value of
76 5.5 nM, -mangostin displayed an IC50 value of 5.12 0.41 M.
A study by (Gopalakrishnan et al., 1997) showed high inhibitory activities of -mangostinderivatives against three phytopathogenic fungi, namely Fusarium oxysporum vasinfectum,
Alternaria tenuis and Dreschlera oryzae, by using 1, 10, 100 and 1000 ppm in the culture
medium. Modification in the bioactivities of the compounds was observed following
substitution in A and C rings.
(Vlietinck et al., 1998) discovered the role of -mangostin as a non-competitive inhibitor of
HIV-1 protease by inhibiting the HIV virus replication cycle.
(Suksamrarn et al., 2003) conducted a study on prenylated xanthones obtained from the
pericarp of the mangosteen fruit to examine the anti-tuberculosis potential. Results showed
that at an MIC value of 6.25 g/mL, -mangostin demonstrated potent inhibitory effect
against Mycobacterium tuberculosis.

(Sakagami et al., 2005)discovered the inhibitory activity of -mangostin against vancomycin

resistant Enterococci (VRE) with an MIC value of 6.25 as well as against Methicillinresistant Staphylococcus aureus (MRSA) with an MIC value of 12.5g/mL.
In addition, (Chin and Kinghorn, 2008b) demonstrated the high efficacy of -mangostin in
terms of its antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA)
with MIC value of 1.95 g/mL and MBC value of 3.91 g/mL.
The activity of -mangostin against the most important microorganism implicated in oral
candidasis, namely Candida albican, in comparison with Clotrimazole and Nystatin was
examined by ( Kaomongkolgit et al., 2009). -mangostin showed to be effective at a
minimum inhibitory concentration of 1,000 g/ml and minimum fungicidal concentration
(MFC) of 2,000 g/ml, exhibiting higher efficiency compared to Clotrimazole and Nystatin.
In determining its cytotoxicity, it was revealed that at 4,000 g/ml, -mangostin was not toxic
to human gingival fibroblast for 480 min. Hence, -mangostin can be a promising agent in
treating oral candidiasis due its low toxicity and strong antifungal activity.
(Arunrattiyakorn et al., 2011) studied the microbial metabolism of -mangostin isolated from
Garcinia mangostana L on fungus and found that two fungi metabolized -mangostin; they
are Colletotrichum gloeosporioides (EYL131) and Neosartorya spathulata (EYR042). The
following four metabolites were produced as a result of incubating -mangostin with C.
gloeosporioides (EYL131): mangostin 3-sulfate (2), mangostanin 6-sulfate (3), 17, 18dihydroxymangostanin 6-sulfate (4) and isomangostanin 3-sulfate (5). Spectroscopic data
analysis was used to elucidate structures of the isolated compounds.

3.5. Anti parasitic and anthelmintic properties

As shown in Table 5, (Taylor and Mangostin, 2006) found that -mangostin showed moderate
in vitro antiplasmodial activity against Plasmodium falciparum with an IC50 value of 17 M.
Table 5.
Anti-parasitic, anthelmintic and anti-obesity properties of -mangostin.
Moderate activity in an in vitro anti-plasmodial against Plasmodium
-mangostin can be an alternative insecticide for the control of Brown
Plant Hopper (BPH).
-mangostin has a larvicidal effect on botanic mosquito sterol carrier
protein-2 inhibitor.
-mangostin has promising activities against the trematodes
Schistosoma mansoni, Echinostoma caproni, and Fasciola hepatica in
vitro(IC50 of 2.915.6 g/mL).
-mangostin has in vitro cytotoxicity against 3T3-L1 cells as well as
inhibiting fatty acid synthase (FAS, EC
Table options

(Taylor and
Mangostin, 2006)
(Bullangpoti et al.,
(Larson et al., 2010)
(Keiser et al., 2012)
(Quan et al., 2012b)

(Bullangpoti et al., 2007) evaluated the extracts of mangosteen pericarp (Garcina

mangostana L.) for their efficiency as an alternative control of Brown Plant Hopper (BPH)
Thailand strain. Toxicity was determined by topical spraying at different nymphal and adult
BPH stages. Compared to the other solvents (hexane, acetone and dichloromethane), ethanol
extract of the mangosteen pericarp exhibited the best control of BPH with LC50 value of 4.5%
w/v (r2 = 0.95) and 3rd instar BPH nymphs. The LC50 value of the active compound, mangostin, was 5.44%w/v (r2 = 0.88). Compared to Imidacloprid (LC50 of 0.0042% w/v (r2 =
0.99)), this extract had less toxicity. In determining toxicity to non-target organisms, it was
found that the extract demonstrated toxicity to the following: guppies (LC50 = 2.53 ppm for
females and 4.27 ppm for males; r2 = 0.97 and 0.97, respectively), bees (LC50 = 4.38% w/v,
r2 = 0.95) and mice (no oral acute toxicity and dermal inflammation, only eye irritation
which occurred in 1 day and returned to normal within 3 days). In vitro detoxification
enzyme activities from BPH, namely carboxylesterase, acetylcholinesterase and glutathiones-transferase, were observed following a 24-hour exposure. Stronger activity was exhibited
by carboxylesterase compared to other enzymes. In each generation, there was an increase of
toxicity in terms of LC50 values for treatments with both the extract and imidacloprid.
Following sequential spraying, each generation showed LC values of 4.22-6.67. The ethanol
extract was kept at different temperatures (4 degrees C, room temperature and 55 degrees C)
for 3 months and it was found that at 55 degrees, the quantity of -mangostin and the BPH
control efficiency was lower. The above results indicate that besides causing minimal
environmental problems, the mangosteen pericarp extract possesses high efficiency and
causes less resistance in BPH, making it a potential alternative insecticide for BPH control.
A study by (Larson et al., 2010) to investigate the larvicidal activity of -mangostin against
third instar larvae of six mosquito species found that the values of median lethal
concentration range from 0.84 to 2.90 ppm. Subsequent to putting -mangostin under semi
field conditions to examine its residual larvicidal activity, -mangostin was found to be
photolytic with a half-life of 53 min in water under full exposure to sunlight. Based on the
results, -mangostin significantly elevated P450 and glutathione S-transferase activities in
larvae, but on the contrary, esterase activity was suppressed. Following a study on its toxicity
against young rats, -mangostin did not demonstrate any adverse effects even at a high
dosage of 80 mg/kg.
The activities of -mangostin and mangostin diacetate, the synthetic derivative, were studied
by ( Keiser et al., 2012). Lack of activity was observed for both -mangostin and mangostin
diacetate against the following nematodes: Heligmosomoides polygyrus (third-stage larvae
(L3), Ancylostoma ceylanicum L3, and Trichuris muris adults. Low activity level was
observed against A. ceylanicum adults (IC50s of 91 g/ml) in vitro, while promising activities
were demonstrated by -mangostin against trematodes: Schistosoma mansoni, Echinostoma
caproni, and Fasciola hepatica in vitro, with IC50 value of 2.915.6 g/ml. Worm burden
reductions, ranging from 0 to 38% (against S. mansoni) and 1154% (against E. caproni)
were achieved by single oral doses of the drugs (400 mg/kg and 800 mg/kg) in vivo.

3.6. Anti-obesity properties

Table 5 displays the in vitro cytotoxicity of -mangostin against 3T3-L1 cells and its
inhibitory effect on fatty acid synthase (FAS, EC as discovered by ( Quan et al.,
2012a). Based on the research, -mangostin with an IC50 value of 20 M had incomplicated
cytotoxicity in apoptotic events such as increase of cell membrane permeability,
mitochondrial membrane potential (m) loss and nuclear chromatin condensation. A decline

of FAS activity in cells also occurred along with this cytotoxicity, which could be rescued by
50 M or 100 M exogenous palmitic acids. This suggested that a-mangostin induced the
apoptosis of 3T3-L1 preadipocytes by inhibiting FAS. -mangostin also showed its ability to
suppress intracellular lipid accumulation in the differentiating adipocytes and stimulated
lipolysis in mature adipocytes; this was associated to its inhibition of FAS as well. It was also
found that the susceptibility of 3T3-L1 preadipocytes towards the cytotoxic effect of mangostin is higher compared to that of the mature adipocytes. Further studies demonstrated
that inhibition of FAS by -mangostin was probably due to stronger action on the ketoacyl
synthase domain and weaker action on the acetyl/malonyl transferase domain. These findings
suggested the usefulness of -mangostin in treating or preventing obesity.

3.7. Treatment of Alzheimers disease (AD)

Wang et al., 2012 discovered that -mangostin attenuated the neurotoxicity induced by A-(140) or A-(1-42) oligomers, with EC50 values of 3.89 nM and 4.14 nM respectively, through
decreased cell viability and impaired neurite outgrowth in primary rat cerebral cortical
neurons in a concentration-dependent manner. The potential of -mangostin to bind to A and
stabilize -helical conformation was demonstrated through molecular docking and dynamics
It was found that -mangostin could dissociate A-(1-40) and A-(1-42) oligomers directly
via blotting with oligomer-specific antibodies. Furthermore, the ability of -mangostin to
block the fibril formation and disturb the pre-formed fibrils was observed through
ThioflavinT fluorescence assay and electron microscopy imaging. All in all, these results
point out the capability of -mangostin to inhibit and dissociate the A aggregation, which
could play a role in its effect of attenuating A oligomers-induced neurotoxicity. This
suggests the great potential of -mangostin to be a candidate for AD treatment.

3.8. Pharmacokinetics Studies

Table 6 shows that in order to determine -mangostin in rat plasma, HPLC-MS assay was
established, with bergamottin as internal standard. The recovery percentage of -mangostin
from the plasma samples was 93.19%. A linear calibration curve, over the range of 20-2000
ng/ml was observed. Total run time was 8 min, and the intra- and inter-assay variability was
less than 9.32% and 9.87%, respectively. -mangostin showed within +15% accuracies when
determined at the concentrations of 70, 850 and 1800ng/ml. Following oral and intravenous
(i.v) injection, pharmacokinetic studies in rats were supported successfully using the rapid,
simple and precise validated method. Non-compartmental and compartmental analyses were
performed, where the two-compartment body model fits well with the (i.v) data. Noncompartmental analysis suggested a short half-life of 4 minutes and a low oral bioavailability
of only 4.24% for -mangostin ( Li et al., 2010). Subsequent to (i.v) administration, mangostin exhibited biphasic disposition in rat plasma, which is subdivided into two phases:
fast distribution and slow elimination. The half-life of the distribution phase was 3min, and
that of the terminal elimination phase 3.5h, indicating a high tissue binding. However, for
oral administration, the bioavailability was so low that it was not possible to obtain a full
concentrationtime profile ( Li et al., 2011).
Table 6.
Pharmacokinetic studies of -mangostin.

A HPLC/MS assay has been established for the determination of -mangostin
in rat plasma after oral and intravenous (i.v) injection. Non-compartmental
analysis was performed.
An LC-MS/MS assay has been established for the determination of mangostin in rat plasma after intravenous (i.v) and oral administration. Both
non-compartmental and compartmental analyses were performed.
Table options

(Li et al.,
(Li et al.,

4. Conclusion
The quest of discovering various pharmacological properties and applications of -mangostin
is an endeavor that continues to develop and progress rapidly. This is evident through the
numerous studies reviewed above as well as others that are continuously being reported.
Nevertheless, the extensive clinical use of -mangostin to treat various human diseases is
confronted with the pharmacokinetic constraints of this particular compound. Despite that,
this predicament is addressed through an exceptional amount of work that is being conducted
by means of unique delivery systems and chemical modifications. Another manner in which
this work can be advantageous to the realm of -mangostin study is through generating
patentable drug constructs that could influence major development and production of mangostin as a drug by the prominent and affluent pharmaceutical companies around the
world. The studies that are reviewed above illustrate the promising qualities and extensive
potential preclinical application of -mangostin which are largely due to its diverse
pharmacological effects on nearly all major organ systems in the animal models. These
effects, accompanied by an equally enormous amount of molecular targets and mechanisms
of action demonstrated in a large host of cell types both in vitro and in vivo, further
substantiated the strong potential of the -mangostin. In addition, preliminary studies have
suggested the safety of this natural compound for human administration, therefore making mangostin a reliable agent that can be used in the prevention and treatment of a wide array of
human pathological conditions, especially inflammatory-based processes or even cancer. In
implying the powerful effect of -mangostin for treating patients, we can perhaps relate to a
quote by Dr. Carl C. Pfeiffer, the author of Pfeiffers Law who stated that For every drug that
benefits a patient, there is a natural substance that can achieve the same effect.

Conflict of interest statement

The authors declare that there are no conflicts of interest.

This study was financially supported by the University of Malaya through the Postgraduate
Research Fund (PPP) grant PG 141-2012B and University Malaya Research Grant RP001C13BIO


o Aisha et al., 2012

o A. Aisha, K. Abu-Salah, Z. Ismail, M.A. Abdul
o In vitro and in vivo anti-colon cancer effects of Garcinia mangostana
xanthones extract
o BMC Complementary and Alternative Medicine, 12 (2012), pp. 104112
o Full Text via CrossRef
o Ames, 1998
o B.N. Ames
o Micronutrients prevent cancer and delay aging
o Toxicology letters, 102 (1998), pp. 518
o Article
PDF (110 K)
View Record in Scopus
Citing articles (236)
o Ames and Gold, 1998
o B.N. Ames, L.S. Gold
o The prevention of cancer
o Drug metabolism reviews, 30 (1998), pp. 201223
o View Record in Scopus

Full Text via CrossRef

Citing articles (30)
o Arunrattiyakorn et al., 2011
o P. Arunrattiyakorn, S. Suksamrarn, N. Suwannasai, H. Kanzaki
o Microbial metabolism of -mangostin isolated from Garcinia mangostana L
o Phytochemistry, 72 (2011), pp. 730734
o Article
PDF (360 K)
View Record in Scopus
Citing articles (9)
o Beckman and Ames, 1998
o K.B. Beckman, B.N. Ames
o The free radical theory of aging matures
o Physiological reviews, 78 (1998), pp. 547581
o View Record in Scopus
Citing articles (2241)
o Borek, 2004

o C. Borek
o Dietary antioxidants and human cancer
o Integrative cancer therapies, 3 (2004), pp. 333341
o View Record in Scopus
Full Text via CrossRef
Citing articles (145)
o Buelna-Chontal et al., 2011
o M. Buelna-Chontal, F. Correa, S. Hernndez-Resndiz, C. Zazueta, J. PedrazaChaverri
o Protective effect of -mangostin on cardiac reperfusion damage by attenuation
of oxidative stress
o Journal of Medicinal Food, 14 (2011), pp. 13701374
o View Record in Scopus
Full Text via CrossRef
Citing articles (6)
o Bullangpoti et al., 2007
o V. Bullangpoti, S. Visetson, J. Milne, M. Milne, C. Sudthongkong, S.
o Effects of alpha-mangostin from mangosteen pericarp extract and imidacloprid
on Nilaparvata lugens (Stal.) and non-target organisms: toxicity and
detoxification mechanism

o Communications in agricultural and applied biological sciences, 72 (2007), pp.

o View Record in Scopus
Citing articles (3)
o Carilli and Yun, 2000
o C. Carilli, M.S. Yun
o The Scatter in the Relationship between Redshift and the Radio-to-Submm
Spectral Index
o Astrophysical Journal, 530 (2000), pp. 618624
o View Record in Scopus
Full Text via CrossRef
Citing articles (89)
o Cassady et al., 1990
o J.M. Cassady, W.M. Baird, C.J. Chang
o Natural products as a source of potential cancer chemotherapeutic and
chemopreventive agents
o Journal of natural products, 53 (1990), pp. 2341
o View Record in Scopus
Full Text via CrossRef

Citing articles (131)

o Chae et al., 2012
o H.-S. Chae, S.-R. Oh, H.-K. Lee, S.H. Joo, Y.-W. Chin
o Mangosteen xanthones, -and -mangostins, inhibit allergic mediators in bone
marrow-derived mast cell
o Food Chemistry, 134 (2012), pp. 397400
o Article
PDF (474 K)
View Record in Scopus
Citing articles (5)
o Chairungsrilerd et al., 1996
o N. Chairungsrilerd, K.I. Furukawa, T. Ohta, S. Nozoe, Y. Ohizumi
o Pharmacological properties of -mangostin, a novel histamine H1 receptor
o European Journal of Pharmacology, 314 (1996), pp. 351356
o Article
PDF (591 K)
View Record in Scopus

Citing articles (52)

o Chen et al., 2008
o L.G. Chen, L.L. Yang, C.C. Wang
o Anti-inflammatory activity of mangostins from (Garcinia mangostana)
o Food and Chemical Toxicology, 46 (2008), pp. 688693
o Article
PDF (170 K)
View Record in Scopus
Citing articles (112)
o Chen et al., 1996
o S.X. Chen, M. Wan, B.N. Loh
o Active constituents against HIV-1 protease from Garcinia mangostana
o Planta Medica-Natural Products and Medicinal Plant Research, 62 (1996), pp.
o View Record in Scopus
Full Text via CrossRef
Citing articles (81)

o Chin and Kinghorn, 2008

o Y.-W. Chin, A.D. Kinghorn
o Structural characterization, biological effects, and synthetic studies on
xanthones from mangosteen (Garcinia mangostana), a popular botanical
dietary supplement
o Mini-reviews in organic chemistry, 5 (2008), pp. 355364
o View Record in Scopus
Full Text via CrossRef
Citing articles (25)
o Collins, 2005
o A.R. Collins
o Antioxidant intervention as a route to cancer prevention
o European Journal of Cancer, 41 (2005), pp. 19231930
o Article
PDF (149 K)
View Record in Scopus
Citing articles (67)
o Cui et al., 2010
o J. Cui, W. Hu, Z. Cai, Y. Liu, S. Li, W. Tao, H. Xiang

o New medicinal properties of mangostins: Analgesic activity and

pharmacological characterization of active ingredients from the fruit hull of
(Garcinia mangostana L)
o Pharmacology Biochemistry and Behavior, 95 (2010), pp. 166172
o Article
PDF (385 K)
View Record in Scopus
Citing articles (27)
o Deschamps et al., 2007
o J.D. Deschamps, J.T. Gautschi, S. Whitman, T.A. Johnson, N.C. Gassner, P.
Crews, T.R. Holman
o Discovery of platelet-type 12-human lipoxygenase selective inhibitors by
high-throughput screening of structurally diverse libraries
o Bioorganic & medicinal chemistry, 15 (2007), pp. 69006908
o Article
PDF (351 K)
View Record in Scopus
Citing articles (32)
o Devi Sampath and Vijayaraghavan, 2007

o P. Devi Sampath, K. Vijayaraghavan

o Cardioprotective effect of -mangostin, a xanthone derivative from
mangosteen on tissue defense system against isoproterenol-induced
myocardial infarction in rats
o Journal of Biochemical and Molecular Toxicology, 21 (2007), pp. 336339
o Full Text via CrossRef
o Dragendorff, 1930
o O. Dragendorff
o ber das Harz von Garcinia Mangostana L
o Justus Liebigs Annalen der Chemie, 482 (1930), pp. 280301
o Full Text via CrossRef
o Fan and Su, 1997
o C.T. Fan, J.D. Su
o Antioxidative mechanism of isolated components from methanol extract of
fruit hulls of Garciniamangostana L
o Journal of the Chinese Agricultural Chemical Society, 35 (1997), pp. 540551
o Fiala et al., 1985
o E.S. Fiala, B.S. Reddy, J.H. Weisburger
o Naturally occurring anticarcinogenic substances in foodstuffs
o Annual review of nutrition, 5 (1985), pp. 295321

o Gopalakrishnan et al., 1980

o C. Gopalakrishnan, D. Shankaranarayanan, L. Kameswaran, S. Nazimudeen
o Effect of mangostin, a xanthone from Garcinia mangostana Linn. in
immunopathological & Inflammatory reactions
o Indian J Exper Biol, 18 (1980), pp. 843846
o Gopalakrishnan et al., 1997
o G. Gopalakrishnan, B. Banumathi, G. Suresh
o Evaluation of the antifungal activity of natural xanthones from Garcinia
mangostana and their synthetic derivatives
o Journal of natural products, 60 (1997), pp. 519524
o Govindachari et al., 1971
o T. Govindachari, P. Kalyanaraman, N. Muthukumaraswamy, B. Pai
o Xanthones of (Garcinia mangostana Linn)
o Tetrahedron, 27 (1971), pp. 39193926
o Hayatsu et al., 1988
o H. Hayatsu, S. Arimoto, T. Negishi
o Dietary inhibitors of mutagenesis and carcinogenesis
o Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis,
202 (1988), pp. 429446

o Hung et al., 2009
o S.H. Hung, K.H. Shen, C.H. Wu, C.L. Liu, Y.W. Shih
o -mangostin suppresses PC-3 human prostate carcinoma cell metastasis by
inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen expression
through the JNK signaling pathway
o Journal of agricultural and food chemistry, 57 (2009), pp. 12911298
o Iinuma et al., 1996
o M. Iinuma, H. Tosa, T. Tanaka, F. Asai, Y. Kobayashl, R. Shimano, K.-I.
o Antibacterial Activity of Xanthones from Guttiferaeous Plants against
Methicillin-resistant Staphylococcus aureus
o Journal of Pharmacy and Pharmacology, 48 (1996), pp. 861865
o Itoh et al., 2008
o T. Itoh, K. Ohguchi, M. Iinuma, Y. Nozawa, Y. Akao
o Inhibitory effect of xanthones isolated from the pericarp of Garcinia
mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation
o Bioorganic & medicinal chemistry, 16 (2008), pp. 45004508
o Jung et al., 2006
o H.A. Jung, B.N. Su, W.J. Keller, R.G. Mehta, A.D. Kinghorn
o Antioxidant xanthones from the pericarp of Garcinia mangostana

o Journal of agricultural and food chemistry, 54 (2006), pp. 20772082

o Kaomongkolgit et al., 2011
o R. Kaomongkolgit, N. Chaisomboon, P. Pavasant
o Apoptotic effect of alpha-mangostin on head and neck squamous carcinoma
o Archives of Oral Biology, 56 (2011), pp. 483490
o Kaomongkolgit et al., 2009
o R. Kaomongkolgit, K. Jamdee, N. Chaisomboon
o Antifungal activity of alpha-mangostin against Candida albicans
o Journal of oral science, 51 (2009), pp. 401406
o Keiser et al., 2012
o J. Keiser, M. Vargas, R. Winter
o Anthelminthic properties of mangostin and mangostin diacetate
o Parasitology International, 61 (2012), pp. 369371
o Krajarng et al., 2012
o A. Krajarng, S. Nilwarankoon, S. Suksamrarn, R. Watanapokasin
o Antiproliferative effect of -mangostin on canine osteosarcoma cells

o Research in Veterinary Science, 93 (2012), pp. 788794

o Larson et al., 2010
o R.T. Larson, J.M. Lorch, J.W. Pridgeon, J.J. Becnel, G.G. Clark, Q. Lan
o The biological activity of alpha-mangostin, a larvicidal botanic mosquito
sterol carrier protein-2 inhibitor
o Journal of medical entomology, 47 (2010), pp. 249257
o Lee et al., 2010
o Y.B. Lee, K.C. Ko, M.D. Shi, Y.C. Liao, T.A. Chiang, P.F. Wu, Y.X. Shih, Y.W.
o -Mangostin, A Novel Dietary Xanthone, Suppresses TPA-Mediated MMP-2
and MMP-9 Expressions through the ERK Signaling Pathway in MCF-7
Human Breast Adenocarcinoma Cells
o Journal of food science, 75 (2010), pp. H13H23
o Li et al., 2010
o L. Li, I. Brunner, A. Han, M. Hamburger, D. Kinghorn, V. Butterweck
o Determination of alpha-mangostin in rat plasma by HPLC-MS and its
application to pharmacokinetic studies
o Planta Medica, 76 (2010), pp. 338346
o Li et al., 2011

o L. Li, I. Brunner, A.R. Han, M. Hamburger, A.D. Kinghorn, R. Frye, V.

o Pharmacokinetics of -mangostin in rats after intravenous and oral application
o Molecular Nutrition & Food Research, 55 (2011), pp. 6774
o Loo, 2003
o G. Loo
o Redox-sensitive mechanisms of phytochemical-mediated inhibition of cancer
cell proliferation (review)
o The Journal of Nutritional Biochemistry, 14 (2003), pp. 6473
o Mahabusarakam et al., 2000
o W. Mahabusarakam, J. Proudfoot, W. Taylor, K. Croft
o Inhibition of lipoprotein oxidation by prenylated xanthones derived from
o Free radical research, 33 (2000), pp. 643651
o Mahabusarakam et al., 1987
o W. Mahabusarakam, P. Wiriyachitra, W.C. Taylor
o Chemical constituents of Garcinia mangostana
o Journal of natural products, 50 (1987), pp. 474478

o Matsumoto et al., 2003

o K. Matsumoto, Y. Akao, E. Kobayashi, K. Ohguchi, T. Ito, T. Tanaka, M.
Iinuma, Y. Nozawa
o Induction of apoptosis by xanthones from mangosteen in human leukemia cell
o Journal of natural products, 66 (2003), pp. 11241127
o Matsumoto et al., 2005
o K. Matsumoto, Y. Akao, K. Ohguchi, T. Ito, T. Tanaka, M. Iinuma, Y. Nozawa
o Xanthones induce cell-cycle arrest and apoptosis in human colon cancer DLD1 cells
o Bioorganic & medicinal chemistry, 13 (2005), pp. 60646069
o Murakami, 1932
o M. Murakami
o ber die Konstitution des Mangostins
o Justus Liebigs Annalen der Chemie, 496 (1932), pp. 122151
o Nabandith et al., 2004
o V. Nabandith, M. Suzui, T. Morioka, T. Kaneshiro, T. Kinjo, K. Matsumoto, Y.
Akao, M. Iinuma, N. Yoshimi
o Inhibitory Effects of Crude alpha-mangostin, a Xanthone Derivative, on Two
Different Categorie of Colon Preneoplastic Lesions Induced by 1, 2dimethylhydrazine in the Rat
o Asian Pacific Journal of Cancer Prevention, 5 (2004), pp. 433438

o Nakabeppu et al., 2006
o Y. Nakabeppu, K. Sakumi, K. Sakamoto, D. Tsuchimoto, T. Tsuzuki, Y.
o Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids
o Biological chemistry, 387 (2006), pp. 373379
o Nakagawa et al., 2007
o Y. Nakagawa, M. Iinuma, T. Naoe, Y. Nozawa, Y. Akao
o Characterized mechanism of -mangostin-induced cell death: Caspaseindependent apoptosis with release of endonuclease-G from mitochondria and
increased miR-143 expression in human colorectal cancer DLD-1 cells
o Bioorganic & medicinal chemistry, 15 (2007), pp. 56205628
o Parveen et al., 1991
o M. Parveen, N.U.-D. Khan, B. Achari, P.K. Dutta
o A triterpene from Garcinia mangostana
o Phytochemistry, 30 (1991), pp. 361362
o Peres et al., 2000
o V. Peres, T.J. Nagem, F.F. de Oliveira
o Tetraoxygenated naturally occurring xanthones

o Phytochemistry, 55 (2000), pp. 683710

o Prez-Rojas et al., 2009
o J.M. Prez-Rojas, C. Cruz, P. Garca-Lpez, D.J. Snchez-Gonzlez, C.M.
Martnez-Martnez, G. Ceballos, M. Espinosa, J. Melndez-Zajgla, J. PedrazaChaverri
o Renoprotection by -mangostin is related to the attenuation in renal
oxidative/nitrosative stress induced by cisplatin nephrotoxicity
o Free radical research, 43 (2009), pp. 11221132
o Quan et al., 2012
o X. Quan, Y. Wang, Y. Liang, W. Tian, Q. Ma, H. Jiang, Y. Zhao
o -mangostin induces apoptosis and suppresses differentiation of 3T3-L1 cells
via inhibiting fatty acid synthase
o PloS one, 7 (2012), pp. 3337633379
o Sakagami et al., 2005
o Y. Sakagami, M. Iinuma, K. Piyasena, H. Dharmaratne
o Antibacterial activity of -mangostin against vancomycin resistant
Enterococci (VRE) and synergism with antibiotics
o Phytomedicine, 12 (2005), pp. 203208
o Snchez-Prez et al., 2010

o Y. Snchez-Prez, R. Morales-Brcenas, C.M. Garca-Cuellar, R. LpezMarure, M. Calderon-Oliver, J. Pedraza-Chaverri, Y.I. Chirino

o The -mangostin prevention on cisplatin-induced apoptotic death in LLC-PK1
cells is associated to an inhibition of ROS production and p53 induction
o Chemico-Biological Interactions, 188 (2010), pp. 144150
o Sato et al., 2004
o A. Sato, H. Fujiwara, H. Oku, K. Ishiguro, Y. Ohizumi
o ALPHA.-Mangostin Induces Ca2+-ATPase-Dependent Apoptosis via
Mitochondrial Pathway in PC12 Cells
o Journal of pharmacological sciences, 95 (2004), pp. 3340
o Schmid, 1855
o W. Schmid
o Ueber das mangostin
o Justus Liebigs Annalen der Chemie, 93 (1855), pp. 8388
o Shankaranarayan et al., 1979
o D. Shankaranarayan, C. Gopalakrishnan, L. Kameswaran
o Pharmacological profile of mangostin and its derivatives
o Arch Internat Pharmaco Therapie, 239 (1979), pp. 257269

o Shibata et al., 2011

o M.-A. Shibata, M. Iinuma, J. Morimoto, H. Kurose, K. Akamatsu, Y. Okuno,
Y. Akao, Y. Otsuki
o -mangostin extracted from the pericarp of the mangosteen (Garcinia
mangostana Linn) reduces tumor growth and lymph node metastasis in an
immunocompetent xenograft model of metastatic mammary cancer carrying a
p53 mutation
o BMC medicine, 9 (2011), pp. 6976
o Shih et al., 2010
o Y.W. Shih, S.T. Chien, P.S. Chen, J.H. Lee, S.H. Wu, L.T. Yin
o -Mangostin Suppresses Phorbol 12-myristate 13-acetate-Induced MMP2/MMP-9 Expressions via v3 Integrin/FAK/ERK and NF-B Signaling
Pathway in Human Lung Adenocarcinoma A549 Cells
o Cell biochemistry and biophysics, 58 (2010), pp. 3144
o Suksamrarn et al., 2006
o S. Suksamrarn, O. Komutiban, P. Ratananukul, N. Chimnoi, N.
Lartpornmatulee, A. Suksamrarn
o Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana
o Chemical and pharmaceutical bulletin, 54 (2006), pp. 301305
o Suksamrarn et al., 2003
o S. Suksamrarn, N. Suwannapoch, W. Phakhodee, J. Thanuhiranlert, P.
Ratananukul, N. Chimnoi, A. Suksamrarn

o Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia

o Chemical and pharmaceutical bulletin, 51 (2003), pp. 857859
o Sundaram et al., 1983
o B. Sundaram, C. Gopalakrishnan, S. Subramanian, D. Shankaranarayanan, L.
o Antimicrobial activities of Garcinia mangostana
o PLANT. MED., 48 (1983), pp. 5960
o Tapsell et al., 2006
o L.C. Tapsell, I. Hemphill, L. Cobiac, C.S. Patch, D.R. Sullivan, M. Fenech, S.
Roodenrys, J.B. Keogh, P.M. Clifton, P.G. Williams, V.A. Fazio, K.E. Inge
o Health benefits of herbs and spices: the past, the present, the future
o The Medical journal of Australia, 185 (2006), pp. 424
o Taylor and Mangostin, 2006
o W.C. Taylor, G. Mangostin
o Prenylated xanthones as potential antiplasmodial substances
o Planta Med, 72 (2006), pp. 912916
o Triggiani et al., 2006

o V. Triggiani, F. Resta, E. Guastamacchia, C. Sabb, B. Licchelli, S.

Ghiyasaldin, E. Tafaro
o Role of antioxidants, essential fatty acids, carnitine, vitamins, phytochemicals
and trace elements in the treatment of diabetes mellitus and its chronic
o Endocrine, metabolic & immune disorders drug targets, 6 (2006), pp. 7793
o Valko et al., 2007
o M. Valko, D. Leibfritz, J. Moncol, M.T.D. Cronin, M. Mazur, J. Telser
o Free radicals and antioxidants in normal physiological functions and human
o The international journal of biochemistry & cell biology, 39 (2007), pp. 4484
o Vlietinck et al., 1998
o A. Vlietinck, T. De Bruyne, S. Apers, L. Pieters
o Plant-derived leading compounds for chemotherapy of human
immunodeficiency virus (HIV) infection
o Planta Medica-Natural Products and Medicinal Plant Research, 64 (1998), pp.
o Wang et al., 2011
o J.J. Wang, B.J.S. Sanderson, W. Zhang
o Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen
(Garcinia mangostana Linn.) on human melanoma cells
o Food and Chemical Toxicology, 49 (2011), pp. 23852391

o Wang et al., 2012
o Y. Wang, Z. Xia, J.-R. Xu, Y.-X. Wang, L.-N. Hou, Y. Qiu, H.-Z. Chen
o -mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates
-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation
o Neuropharmacology, 62 (2012), pp. 871881
o Williams et al., 1995
o P. Williams, M. Ongsakul, J. Proudfoot, K. Croft, L. Beilin
o Mangostin inhibits the oxidative modification of human low density
o Free radical research, 23 (1995), pp. 175184
o Yates and Stout, 1958
o P. Yates, G.H. Stout
o The Structure of Mangostin1
o Journal of the American Chemical Society, 80 (1958), pp. 16911700
o Yoo et al., 2011
o J.-H. Yoo, K. Kang, E.H. Jho, Y.-W. Chin, J. Kim, C.W. Nho
o - and -Mangostin inhibit the proliferation of colon cancer cells via -catenin
gene regulation in Wnt/cGMP signalling

o Food Chemistry, 129 (2011), pp. 15591566

o Yoshikawa et al., 1994
o M. Yoshikawa, E. Harada, A. Miki, K. Tsukamoto, S. Liang, J. Yamahara, N.
o Antioxidant Constituents from the Fruit Hulls of Mangosteen (Garcinia
mangostana L.) Originated in Vietnam
o Journal of the Pharmaceutical Society of Japan-Yakugaku Zasshi, 114 (1994),
p. 129
Corresponding author.
Copyright 2014 Production and hosting by Elsevier B.V.
Note to users: Accepted manuscripts are Articles in Press that have been peer reviewed and
accepted for publication by the Editorial Board of this publication. They have not yet been
copy edited and/or formatted in the publication house style, and may not yet have the full
ScienceDirect functionality, e.g., supplementary files may still need to be added, links to
references may not resolve yet etc. The text could still change before final publication.
Although accepted manuscripts do not have all bibliographic details available yet, they can
already be cited using the year of online publication and the DOI, as follows: author(s),
article title, Publication (year), DOI. Please consult the journal's reference style for the exact
appearance of these elements, abbreviation of journal names and use of punctuation.
When the final article is assigned to an volumes/issues of the Publication, the Article in Press
version will be removed and the final version will appear in the associated published
volumes/issues of the Publication. The date the article was first made available online will be
carried over.