Research Abstracts on “Mangostin”

Mangosteens and Xanthones

1:  Hamada M, Iikubo K, Ishikawa Y, Ikeda A, Umezawa K, Nishiyama S. 
 Biological activities of alpha-mangostin derivatives against acidic
sphingomyelinase.

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3151-3. 
PMID: 12951083 [PubMed - in process] 

Biological activities of alpha-mangostin derivatives against 
acidic sphingomyelinase.


Hamada M, Iikubo K, Ishikawa Y, Ikeda A, Umezawa K, Nishiyama S.


Department of Chemistry, Faculty of Science and Technology, Keio University, 
Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan.


Deprenyl and benzofenone-type congeners of alpha-mangostin 1 have been synthesized to 
understand their role for the inhibitory activity against sphingomyelinase (SMase). 
While removal of the prenyl group of the right side (11 and 12) caused loss of the 
selectivity between ASMase (acidic sphingomyelinase) and NSMase (neutral sphingomyelinase), 
the prenyl group of the left side appeared to increase the inhibitory activities (16 and 17).

PMID: 12951083 [PubMed - in process]
2:  Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, Iinuma M,
Nozawa Y. 

 Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines.
j Nat Prod. 2003 Aug;66(8):1124-7. 

PMID: 12932141 [PubMed - in process] 

Induction of apoptosis by xanthones from mangosteen in human 
leukemia cell lines.

Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, Iinuma M, Nozawa Y.

Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, 
Gifu 504-0838, Japan. kmatsumoto@giib.or.jp 

We examined the effects of six xanthones from the pericarps of mangosteen, 
Garcinia mangostana, on the cell growth inhibition of human leukemia cell line HL60. 
All xanthones displayed growth inhibitory effects. Among them, alpha-mangostin 
showed complete inhibition at 10 microM through the induction of apoptosis.

PMID: 12932141 [PubMed - in process]

3:  Nakatani K, Nakahata N, Arakawa T, Yasuda H, Ohizumi Y. 
Inhibition of cyclooxygenase and prostaglandin E2 synthesis 
by gamma-mangostin,a xanthone derivative in mangosteen, in 
C6 rat glioma cells.

Biochem Pharmacol. 2002 Jan 1;63(1):73-9. 
PMID: 11754876 [PubMed - indexed for MEDLINE] 

Inhibition of cyclooxygenase and prostaglandin E2 synthesis 
by gamma-mangostin, a xanthone derivative in mangosteen, 
in C6 rat glioma cells.

Nakatani K, Nakahata N, Arakawa T, Yasuda H, Ohizumi Y.

Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical 
Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, 980-8578, Sendai, Japan.

The fruit hull of mangosteen, Garcinia mangostana L., has been used for many years 
as a medicine for treatment of skin infection, wounds, and diarrhea in Southeast Asia. 
In the present study, we examined the effect of gamma-mangostin, a tetraoxygenated 
diprenylated xanthone contained in mangosteen, on arachidonic acid (AA) cascade in 
C6 rat glioma cells. gamma-Mangostin had a potent inhibitory activity of prostaglandin E2 (
PGE2) release induced by A23187, a Ca2+ ionophore. The inhibition was concentration-dependent, 
with the IC50 value of about 5 microM. gamma-Mangostin had no inhibitory effect on 
A23187-induced phosphorylation of p42/p44 extracellular signal regulated kinase/mitogen-activated 
protein kinase or on the liberation of [14C]-AA from the cells labeled with [14C]-AA. 
However, gamma-mangostin concentration-dependently inhibited the conversion of AA to PGE2 
in microsomal preparations, showing its possible inhibition of cyclooxygenase (COX). 
In enzyme assay in vitro, gamma-mangostin inhibited the activities of both constitutive 
COX (COX-1) and inducible COX (COX-2) in a concentration-dependent manner, with the IC50 
values of about 0.8 and 2 microM, respectively. Lineweaver-Burk plot analysis indicated 
that gamma-mangostin competitively inhibited the activities of both COX-1 and -2. 
This study is a first demonstration that gamma-mangostin, a xanthone derivative, 
directly inhibits COX activity.


PMID: 11754876 [PubMed - indexed for MEDLINE]

4:  Mahabusarakam W, Proudfoot J, Taylor W, Croft K. 

 Inhibition of lipoprotein oxidation by prenylated xanthones derived from
mangostin. Free Radic Res. 2000 Nov;33(5):643-59. 
PMID: 11200095 [PubMed - indexed for MEDLINE] 

Inhibition of lipoprotein oxidation by prenylated xanthones 
derived from mangostin.

Mahabusarakam W, Proudfoot J, Taylor W, Croft K.

Chemistry Department, Prince of Songkla University, Hat Yai, Thailand.

Oxidative damage is thought to play a critical role in cardiovascular and other 
chronic diseases. This has led to considerable interest in the antioxidant 
activity of dietary compounds. Flavonoids have received the most attention and 
much is known about the structural requirements for antioxidant activity. 
However, little is known about the antioxidant activity of other plant derived 
phenolic compounds such as the xanthones. We have previously shown that the 
prenylated xanthone, mangostin, can inhibit the oxidation of low density 
lipoprotein. In order to examine the effects of structure modification on 
antioxidant activity of this class of compound we have prepared a number of 
derivatives of mangostin and tested antioxidant activity in an isolated LDL and 
plasma assay. The results of this study show that structural modification of 
mangostin can have a profound effect on antioxidant activity. Derivatisation 
of the C-3 and C-6 hydroxyl groups with either methyl, acetate, propane diol or 
nitrile substantially reduces antioxidant activity. In contrast, derivatisation 
of C-3 and C-6 with aminoethyl derivatives enhanced antioxidant activity, which 
may be related to changes in solubility. Cyclisation of the prenyl chains had 
little influence on antioxidant activity.

PMID: 11200095 [PubMed - indexed for MEDLINE]

5:  Okudaira C, Ikeda Y, Kondo S, Furuya S, Hirabayashi Y, Koyano T, Saito Y,
Umezawa K.
 Inhibition of acidic sphingomyelinase by xanthone compounds isolated from
Garcinia speciosa.
J Enzyme Inhib. 2000;15(2):129-38. 
PMID: 10938539 [PubMed - indexed for MEDLINE] 

Inhibition of acidic sphingomyelinase by xanthone compounds isolated 
from Garcinia speciosa.

Okudaira C, Ikeda Y, Kondo S, Furuya S, Hirabayashi Y, Koyano T, Saito Y, Umezawa K.


Department of Applied Chemistry, Faculty of Science and Technology, 
Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan.

Sphingomyelinase is considered to be involved in the regulation of 
apoptosis (cell death) and cell growth. In the course of our screening 
for acidic sphingomyelinase inhibitors we isolated three xanthone compounds, 
alpha-mangostin, cowanin, and cowanol, from the bark of Garcinia speciosa. 
These compounds competitively inhibited bovine brain-derived acidic sphingomyelinase 
with IC(50) values of 14.1, 19.2, and 10.9 microM, respectively and inhibited the 
acidic sphingomyelinase more effectively than the neutral sphingomyelinase of bovine brain. 
alpha-Mangostin inhibited the acidic sphingomyelinase in the most selective manner. 
alpha-Mangostin was chemically modified and its structure-activity relationships are discussed.

PMID: 10938539 [PubMed - indexed for MEDLINE]

6:  Lu ZX, Hasmeda M, Mahabusarakam W, Ternai B, Ternai PC, Polya GM. 

 Inhibition of eukaryote protein kinases and of a cyclic nucleotide-binding
phosphatase by prenylated xanthones.
Chem Biol Interact. 1998 Jul 3;114(1-2):121-40. 
PMID: 9744560 [PubMed - indexed for MEDLINE] 

Inhibition of eukaryote protein kinases and of a cyclic 
nucleotide-binding phosphatase by prenylated xanthones.

Lu ZX, Hasmeda M, Mahabusarakam W, Ternai B, Ternai PC, Polya GM.
School of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.

A series of prenylated xanthones are variously potent inhibitors of the 
catalytic subunit (cAK) of rat liver cyclic AMP-dependent protein kinase (PKA), 
rat brain Ca2+ and phospholipid-dependent protein kinase C (PKC), chicken gizzard 
myosin light chain kinase (MLCK), wheat embryo Ca2+-dependent protein kinase (CDPK) 
and potato tuber cyclic nucleotide-binding phosphatase (Pase). The prenylated 
xanthones examined are mostly derivatives of alpha-mangostin in which the 3-hydroxyl 
and 6-hydroxyl are variously substituted with groups R or R', respectively, or 
derivatives of 3-isomangostin (mangostanol) in which the 9-hydroxyl is substituted 
with groups R' or the prenyl side chain is modified. The most potent inhibitors of 
cAK have non-protonatable and relatively small R' and R groups. Conversely, the most 
potent inhibitors of PKC and MLCK have bulkier and basic R' groups. Some prenylated 
xanthones are also potent inhibitors of CDPK. PKC and cAK are competitively 
inhibited by particular prenylated xanthones whereas the compounds that are 
the most potent inhibitors of MLCK and CDPK are non-competitive inhibitors. 
Prenylated xanthones having relatively small and non-protonatable R' and R 
groups inhibit a high-affinity cyclic nucleotide binding Pase in a non-competitive fashion.

     (Protein kinases make up a veritable treasure trove of targets for a variety of indications, including diabetes,
inflammatory disorders, and especially cancer. )

PMID: 9744560 [PubMed - indexed for MEDLINE]
7:  Hopert AC, Beyer A, Frank K, Strunck E, Wunsche W, Vollmer G. 
 Characterization of estrogenicity of phytoestrogens in an endometrial-derived
experimental model.
Environ Health Perspect. 1998 Sep;106(9):581-6. 
PMID: 9721258 [PubMed - indexed for MEDLINE]

Characterization of estrogenicity of phytoestrogens in an 
endometrial-derived experimental model.

Hopert AC, Beyer A, Frank K, Strunck E, Wunsche W, Vollmer G.

Institut fur Molekulare Medizin, Medizinische Universitat zu Lubeck, Lubeck, Germany.

Severe developmental and reproductive disorders in wild animals have been linked 
to high exposure to persistent environmental chemicals with hormonal activity. 
These adverse effects of environmental estrogens have raised considerable concern 
and have received increasing attention. Although numerous chemicals with the 
capacity to interfere with the estrogen receptor (ER) have been identified, 
information on their molecular mechanism of action and their relative potency 
is rather limited. For the endometrium, the lack of information is due to the 
lack of a suitable experimental model. We investigated the functions of phytoestrogens 
in an endometrial-derived model, RUCA-I rat endometrial adenocarcinoma cells. 
The cells were cultured on a reconstituted basement membrane to preserve their 
functional differentiation and estrogen responsiveness. We assessed the relative 
binding affinity to the estrogen receptor of the selected phytoestrogens coumestrol, 
genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a 
competitive Scatchard analysis. The following affinity ranking was measured: 
17beta-estradiol >>> coumestrol > genistein > daidzein >>> mangostin. In addition, 
we investigated the capacity of these compounds to promote the increased production 
of complement C3, a well-known estradiol-regulated protein of the rat endometrium. 
All substances tested increased the production of complement C3, although different 
concentrations were necessary to achieve equivalent levels of induction compared to 
estradiol. Mechanistically we were able to demonstrate that the increase of complement 
C3 production was mediated by primarily increasing its steady-state mRNA level. These 
findings indicate that RUCA-I cells represent a sensitive model system to elucidate 
relative potencies and functions of environmental estrogens in an endometrium-derived model.

PMID: 9721258 [PubMed - indexed for MEDLINE] 

8:  Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y. 
 Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A
receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of
mice.

Br J Pharmacol. 1998 Mar;123(5):855-62. 
PMID: 9535013 [PubMed - indexed for MEDLINE]

Effect of gamma-mangostin through the inhibition of 
5-hydroxy-tryptamine2A receptors in 
5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice.

Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y.

Department of Molecular Biology, Faculty of Pharmaceutical Sciences, 
Tohoku University, Sendai, Japan.

1. Intracerebronventricular (i.c.v.) injection of gamma-mangostin (10-40 nmol/mouse), 
a major compound of the fruit hull of Garcinia mangostana Lin., like ketanserin 
(10, 20 nmol/mouse, i.c.v.) inhibited 5-fluoro-alpha-methyltryptamine (5-FMT) 
(45 mg kg(-1), i.p.)-induced head-twitch response in mice in the presence or 
absence of citalopram (a 5-hydroxytryptamine (5-HT)-uptake inhibitor). 2. 
Neither the 5-FMT- nor the 8-hydroxy-2-(di-n-propylamino)tetralin 
5-HT1A-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) 
was affected by gamma-mangostin or ketanserin. 3. The locomotor activity 
stimulated by 5-FMT through the activation of alpha1-adrenoceptors did not 
alter in the presence of gamma-mangostin. 4. 5-HT-induced inositol phosphates 
accumulation in mouse brain slices was abolished by ketanserin. Gamma-mangostin 
caused a concentration-dependent inhibition of the inositol phosphates accumulation. 
5. Gamma-mangostin caused a concentration-dependent inhibition of the binding of 
[3H]-spiperone, a specific 5-HT2A receptor antagonist, to mouse brain membranes. 
6. Kinetic analysis of the [3H]-spiperone binding revealed that gamma-mangostin 
increased the Kd value without affecting the Bmax value, indicating the mode of 
the competitive nature of the inhibition by gamma-mangostin. 7. These results 
suggest that gamma-mangostin inhibits 5-FMT-induced head-twitch response in mice 
by blocking 5-HT2A receptors not by blocking the release of 5-HT from the 
central neurone. Gamma-mangostin is a promising 5-HT2A receptor antagonist 
in the central nervous system.

PMID: 9535013 [PubMed - indexed for MEDLINE]

9:  Vlietinck AJ, De Bruyne T, Apers S, Pieters LA. 


 Plant-derived leading compounds for chemotherapy of human immunodeficiency
virus (HIV) infection.
Planta Med. 1998 Mar;64(2):97-109. Review. 
PMID: 9525100 [PubMed - indexed for MEDLINE]

Plant-derived leading compounds for chemotherapy of
human immunodeficiency virus (HIV) infection.

Vlietinck AJ, De Bruyne T, Apers S, Pieters LA.

Department of Pharmaceutical Sciences, University of Antwerp (UA), Belgium. vlietink@uta.ua.ac.be

Many compounds of plant origin have been identified that inhibit different stages in the replication
cycle of human immunodeficiency virus (HIV): 1) virus adsorption: chromone alkaloids
(schumannificine), isoquinoline alkaloids (michellamines), sulphated polysaccharides and
polyphenolics, flavonoids, coumarins (glycocoumarin, licopyranocoumarin) phenolics
(caffeic acid derivatives, galloyl acid derivatives, catechinic acid derivatives), tannins and
triterpenes (glycyrrhizin and analogues, soyasaponin and analogues); 2) virus-cell fusion:
 lectins (mannose- and N-acetylglucosamine-specific) and triterpenes (betulinic acid and analogues);
3) reverse transcription; alkaloids (benzophenanthridines, protoberberines, isoquinolines, quinolines),
coumarins (calanolides and analogues), flavonoids, phloroglucinols, lactones (protolichesterinic acid),
tannins, iridoids (fulvoplumierin) and triterpenes; 4) integration: coumarins
(3-substituted-4-hydroxycoumarins), depsidones, O-caffeoyl derivatives, lignans
(arctigenin and analogues) and phenolics (curcumin); 5) translation: single chain ribosome
inactivating proteins (SCRIP's); 6) proteolytic cleavage (protease inhibition): saponins
(ursolic and maslinic acids), xanthones (mangostin and analogues) and coumarins; 7)
glycosylation: alkaloids including indolizidines (castanospermine and analogues), piperidines
(1-deoxynojirimicin and analogues) and pyrrolizidines (australine and analogues); 8)
assembly/release: naphthodianthrones (hypericin and pseudohypericin), photosensitisers
(terthiophenes and furoisocoumarins) and phospholipids. The target of action of several anti-HIV
substances including alkaloids (O-demethyl-buchenavianine, papaverine), polysaccharides
(acemannan), lignans (intheriotherins, schisantherin), phenolics (gossypol, lignins, catechol dimers
such as peltatols, naphthoquinones such as conocurvone) and saponins (celasdin B, Gleditsia and
Gymnocladus saponins), has not been elucidated or does not fit in the proposed scheme.
Only a very few of these plant-derived anti-HIV products have been used in a limited number
of patients suffering from AIDS viz. glycyrrhizin, papaverine, trichosanthin, castanospermine,
N-butyl-1-deoxynojirimicin and acemannan.

Publication Types:
·         Review
·         Review, Academic

PMID: 9525100 [PubMed - indexed for MEDLINE] 

10:  Furukawa K, Chairungsrilerd N, Ohta T, Nozoe S, Ohizumi Y. 
 [Novel types of receptor antagonists from the medicinal plant Garcinia
mangostana]


Nippon Yakurigaku Zasshi. 1997 Oct;110 Suppl 1:153P-158P. Japanese. 
PMID: 9503424 [PubMed - indexed for MEDLINE]

[Novel types of receptor antagonists from the 
medicinal plant Garcinia mangostana]

[Article in Japanese]

Furukawa K, Chairungsrilerd N, Ohta T, Nozoe S, Ohizumi Y.

Department of Pharmaceutical Molecular Biology, Faculty of 
Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

A crude methanolic extract of the fruit hull of 
Garcinia mangostana L. inhibited the contraction of 
the isolated rabbit aorta induced by histamine and serotonin. 
The extract has been fractionated by silica gel chromatography, 
monitoring the pharmacological activity to give active compounds. 
On the basis of physicochemical data, the active substances 
were identified as alpha-mangostin and gamma-mangostin. To 
define the pharmacological properties of alpha-mangostin, the 
effect of alpha-mangostin on both histamine H1 and H2 receptors 
were examined by monitoring the mechanical responses of smooth 
muscles and measuring the radioligand binding to cultured vascular 
smooth muscle cells. The results suggest that alpha-mangostin acts 
as a selective and competitive histamine H1 receptor antagonist. 
The pharmacological actions of gamma-mangostin on 5-HT receptors 
were also investigated by using contractile response of vascular 
smooth muscle, platelet aggregation and radioligand binding studies. 
The results provide the evidence that gamma-mangostin is a selective 
and competitive 5-HT2A receptor antagonist. It is of great interest 
that the structures of alpha-mangostin and gamma-mangostin free from 
nitrogen atom are not resemble to the common structures of histamine 
and serotonin receptor antagonists. alpha-Mangostin and gamma-mangostin 
may become novel types of lead compounds for histamine and serotonin 
receptor antagonists.

PMID: 9503424 [PubMed - indexed for MEDLINE] 


11:  Likhitwitayawuid K, Phadungcharoen T, Krungkrai J. 
 Antimalarial xanthones from Garcinia cowa.
Planta Med. 1998 Feb;64(1):70-2. 
PMID: 9491769 [PubMed - indexed for MEDLINE]

Antimalarial xanthones from Garcinia cowa.

Likhitwitayawuid K, Phadungcharoen T, Krungkrai J.

Five xanthones from the bark of Garcinia cowa, namely 7-O-methylgarcinone E (1), cowanin
(2), cowanol (3), cowaxanthone (4), and beta-mangostin (5), were found to possess in vitro
antimalarial activity against Plasmodium falciparum with IC50 values ranging from 1.50 to
3.00 micrograms/ml. Complete 1H- and 13C-NMR assignments of these compounds are also reported.

Publication Types:

·         Letter

PMID: 9491769 [PubMed - indexed for MEDLINE]
12:  Chairungsrilerd N, Furukawa KI, Ohta T, Nozoe S, Ohizumi Y. 
 Gamma-mangostin, a novel type of 5-hydroxytryptamine 2A receptor antagonist.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Jan;357(1):25-31. 
PMID: 9459569 [PubMed - indexed for MEDLINE] 

Gamma-mangostin, a novel type of 5-hydroxytryptamine 
2A receptor antagonist.

Chairungsrilerd N, Furukawa KI, Ohta T, Nozoe S, Ohizumi Y.

Department of Pharmaceutical Molecular Biology, Faculty of 
Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

Gamma-mangostin, purified from the fruit hull of the medicinal 
plant Garcinia mangostana caused a parallel rightwards shift of 
the concentration/response curve for the contraction elicited by 
5-hydroxytryptamine (5-HT) in the rabbit aorta (pA2 = 8.2) 
without affecting the contractile responses to KCl, phenylephrine 
(alpha1) or histamine (H1). The perfusion pressure response of rat 
coronary artery to 5-HT (5-HT2A) was reduced concentration dependently 
by gamma-mangostin (IC50 = 0.32 microM). 5-HT amplified, ADP-induced 
aggregation of rabbit platelets (5-HT2A) was inhibited by gamma-mangostin 
(IC50 = 0.29 microM), whereas that induced by thrombin was not affected, 
nor did gamma-mangostin affect 5-HT-induced contraction of the guinea-pig 
ileum (5-HT3)in the presence of 5-HT1, 5-HT2 and 5-HT4 receptor antagonists. 
Furthermore, 5-HT-induced contraction of the rat fundus (5-HT2B) and 
5-HT-induced relaxation of the rabbit aorta in the presence of ketanserin 
(5-HT1) and carbachol-induced contraction of the guinea-pig ileum (muscarinic M3) 
were not affected by gamma-mangostin (5 microM). Gamma-mangostin inhibited 
[3H]spiperone binding to cultured rat aortic myocytes (IC50 = 3.5 nM). 
The Kd for [3H]spiperone binding was increased by gamma-mangostin 
(3 nM) from 11.7 to 27.4 nM without affecting Bmax. These results suggest 
that gamma-mangostin is a novel competitive antagonist, free from a nitrogen 
atom, for the 5-HT2A receptors in vascular smooth muscles and platelets.

PMID: 9459569 [PubMed - indexed for MEDLINE]

13:  Gopalakrishnan G, Banumathi B, Suresh G. 
 Evaluation of the antifungal activity of natural xanthones from Garcinia
mangostana and their synthetic derivatives.
J Nat Prod. 1997 May;60(5):519-24. 
PMID: 9213587 [PubMed - indexed for MEDLINE]

Evaluation of the antifungal activity of natural xanthones 
from Garcinia mangostana and their synthetic derivatives.

Gopalakrishnan G, Banumathi B, Suresh G.

Centre for Agrochemical Research, SPIC Science Foundations, Madras, India.

The antifungal activity of several xanthones isolated from the fruit 
hulls of Garcinia mangostana and some derivatives of mangostin against 
three phytopathogenic fungi, Fusarium oxysporum vasinfectum, 
Alternaria tenuis, and Dreschlera oryzae, has been evaluated. 
The natural xanthones showed good inhibitory activity against 
the three fungi. Substitution in the A and C rings has been 
shown to modify the bioactivities of the compounds.

PMID: 9213587 [PubMed - indexed for MEDLINE]
14:  Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y. 
 Pharmacological properties of alpha-mangostin, a novel histamine H1 receptor
antagonist.


Eur J Pharmacol. 1996 Oct 31;314(3):351-6. 
PMID: 8957258 [PubMed - indexed for MEDLINE]

Pharmacological properties of alpha-mangostin, 
a novel histamine H1 receptor antagonist.

Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y.

Department of Pharmaceutical Molecular Biology, Faculty of 
Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

In the isolated rabbit thoracic aorta and guinea-pig trachea, 
alpha-mangostin inhibited histamine-induced contractions in a 
concentration-dependent manner in the presence or absence of 
cimetidine, a histamine H2 receptor antagonist. But KCl-, 
phenylephrine- or carbachol-induced contractions were not 
affected by alpha-mangostin. The concentration-contractile 
response curve for histamine was shifted to the right in a 
parallel manner by alpha-mangostin. In the presence of 
chlorpheniramine, a histamine H1 receptor antagonist, 
alpha-mangostin did not affect the relaxation of the rabbit 
aorta induced by histamine. In the guinea-pig trachea, 
alpha-mangostin had no effect on the relaxation induced by 
dimaprit, a histamine H2 receptor agonist. alpha-Mangostin 
caused a concentration-dependent inhibition of the binding 
of [3H]mepyramine, a specific histamine H1 receptor antagonist 
to rat aortic smooth muscle cells. Kinetic analysis of 
[3H]mepyramine binding indicated the competitive inhibition by 
alpha-mangostin. These results suggest that alpha-mangostin is a 
novel competitive histamine H1 receptor antagonist in smooth muscle cells.

PMID: 8957258 [PubMed - indexed for MEDLINE]
15:  Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y. 
 Histaminergic and serotonergic receptor blocking substances 
from the medicinal plant Garcinia mangostana.

Planta Med. 1996 Oct;62(5):471-2. 
PMID: 8923814 [PubMed - indexed for MEDLINE]

Histaminergic and serotonergic receptor blocking substances 
from the medicinal plant Garcinia mangostana.

Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y.

A crude methanolic extract of the fruit hull of Mangosteen, Garcinia mangostana L. 
inhibited the contractions of isolated thoracic rabbit aorta induced by histamine and 
serotonin. The extract of the fruit hull has been fractionated by silica gel chromatography, 
monitoring the pharmacological activity to give alpha- and gamma-mangostin. On the basis 
of pharmacological data, it is suggested that alpha-mangostin and gamma-mangostin 
are a histaminergic and a serotonergic receptor blocking agent, respectively.

Publication Types:

·         Letter

PMID: 8923814 [PubMed - indexed for MEDLINE]
16:  Iinuma M, Tosa H, Tanaka T, Asai F, Kobayashi Y, Shimano R, Miyauchi K. 
Antibacterial activity of xanthones from guttiferaeous plants against
methicillin-resistant Staphylococcus aureus.
J Pharm Pharmacol. 1996 Aug;48(8):861-5. 
PMID: 8887739 [PubMed - indexed for MEDLINE]

Antibacterial activity of xanthones from guttiferaeous 
plants against methicillin-resistant Staphylococcus aureus.

Iinuma M, Tosa H, Tanaka T, Asai F, Kobayashi Y, Shimano R, Miyauchi K.

Department of Pharmacognosy, Gifu Pharmaceutical University, Japan.

Extracts of Garcinia mangostana (Guttiferae) showing inhibitory 
effects against the growth of S. aureus NIHJ 209p were fractionated 
according to guidance obtained from bioassay and some of the 
components with activity against methicillin-resistant Staphylococcus 
aureus (MRSA) were characterized. One active isolate, alpha-mangostin, 
a xanthone derivative, had a minimum inhibitory concentration (MIC) 
of 1.57-12.5 micrograms mL-1. Other related xanthones were also examined 
to determine their anti-MRSA activity. Rubraxanthone, which was isolated 
from Garcinia dioica and has a structure similar to that of alpha-mangostin, 
had the highest activity against staphylococcal strains (MIC = 0.31-1.25 micrograms mL-1), 
an activity which was greater than that of the antibiotic vancomycin 
(3.13-6.25 micrograms mL-1). The inhibitory effect against strains of 
MRSA of two of the compounds when used in conjunction with other antibiotics 
was also studied. The anti-MRSA activity of alpha-mangostin was clearly 
increased by the presence of vancomycin; this behaviour was not observed for 
rubraxanthone. The strong in-vitro antibacterial activity of xanthone derivatives 
against both methicillin-resistant and methicillin-sensitive Staphylococcus aureus 
suggests the compounds might find wide pharmaceutical use.

PMID: 8887739 [PubMed - indexed for MEDLINE]
17:  Furukawa K, Shibusawa K, Chairungsrilerd N, Ohta T, Nozoe S, Ohizumi Y. 

 The mode of inhibitory action of alpha-mangostin, a novel inhibitor, on the
sarcoplasmic reticulum Ca(2+)-pumping ATPase from rabbit skeletal muscle.

Jpn J Pharmacol. 1996 Aug;71(4):337-40. 
PMID: 8886932 [PubMed - indexed for MEDLINE]

The mode of inhibitory action of alpha-mangostin, a novel 
inhibitor, on the sarcoplasmic reticulum Ca(2+)-pumping ATPase 
from rabbit skeletal muscle.

Furukawa K, Shibusawa K, Chairungsrilerd N, Ohta T, Nozoe S, Ohizumi Y.

Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical 
Sciences, Tohoku University, Sendai, Japan.

alpha-Mangostin, the principal ingredient of the fruit hull of 
Garcinia mangostana, caused a concentration-dependent decrease in the 
activities of both Ca(2+)-ATPase and Ca(2+)-transport of the sarcoplasmic 
reticulum from rabbit skeletal muscle with an IC50 value of 5 microM. 
Neither Ca2+ release nor other enzyme activities were affected by alpha-mangostin. 
Kinetic analysis of the inhibitory effects of alpha-mangostin on Ca(2+)-ATPase 
suggests that the inhibition of the ATPase is a noncompetitive-type with respect 
to ATP or Ca2+. alpha-Mangostin may become a useful pharmacological tool for 
clarifying the physiological functions of Ca(2+)-pumping ATPase and sarcoplasmic reticulum.

PMID: 8886932 [PubMed - indexed for MEDLINE] 

18:  Chen SX, Wan M, Loh BN. 
 Active constituents against HIV-1 protease from Garcinia mangostana.
Planta Med. 1996 Aug;62(4):381-2. 
PMID: 8792678 [PubMed - indexed for MEDLINE] 

Active constituents against HIV-1 protease from Garcinia mangostana.

Chen SX, Wan M, Loh BN.

The ethanol extract of Garcinia mangostana L. (Guttiferae) showed potent inhibitory activity against
HIV-1 protease. The activity-guided purification of the extract resulted in the isolation of two active,
known compounds. The chemical structures of the isolated compounds were established by
spectroscopic analyses as mangostin (IC50 = 5.12 +/- 0.41 microM) and gamma-mangostin
(IC50 = 4.81 +/- 0.32 microM). The type of inhibition by both compounds is noncompetitive.

PMID: 8792678 [PubMed - indexed for MEDLINE] 
19:  Williams P, Ongsakul M, Proudfoot J, Croft K, Beilin L.
 Mangostin inhibits the oxidative modification of human low
density lipoprotein.
Free Radic Res. 1995 Aug;23(2):175-84.
PMID: 7581813 [PubMed - indexed for MEDLINE]

 Mangostin inhibits the oxidative modification of 
human low density lipoprotein.

Williams P, Ongsakul M, Proudfoot J, Croft K, Beilin L.

University of Western Australia, Department of Medicine, 
Royal Perth Hospital, Australia.

The oxidation of low density lipoprotein (LDL) may play an important 
role in atherosclerosis. We investigated the possible antioxidant 
effects of mangostin, isolated from Garcinia mangostana, on metal 
ion dependent (Cu2+) and independent (aqueous peroxyl radicals) 
oxidation of human LDL. Mangostin prolonged the lagtime to both 
metal ion dependent and independent oxidation of LDL in a dose 
dependent manner over 5 to 50 microM as monitored by the formation 
of conjugated dienes at 234 nm (P < 0.001). There was no significant 
effect of mangostin on the rate at which conjugated dienes were formed 
in the uninhibited phase of oxidation. Levels of thiobarbituric reactive 
substances (TBARS) generated in LDL were measured 4 and 24 hours after 
oxidation with 5 microM Cu2+ in the presence or absence of 50 microM or 
100 microM mangostin. We observed an inhibition of TBARS formation with 
100 microM mangostin at 4 hours (P = 0.027) but not at 24 hours 
(P = 0.163). Similar results were observed in the presence of 50 
microM mangostin. Mangostin, at 100 microM, retarded the relative 
electrophoretic mobility of LDL at both 4 and 24 hours after Cu2+ 
induced oxidation. Mangostin (100 microM) significantly inhibited the 
consumption of alpha-tocopherol in the LDL during Cu2+ initiated oxidation 
over a 75 minute period (P < 0.001). From these results, we conclude that 
mangostin is acting as a free radical scavenger to protect the LDL from 
oxidative damage in this in vitro system.

PMID: 7581813 [PubMed - indexed for MEDLINE]
20:  Jinsart W, Ternai B, Buddhasukh D, Polya GM. 
 Inhibition of wheat embryo calcium-dependent 
protein kinase and other kinases by mangostin and gamma-mangostin.
Phytochemistry. 1992 Nov;31(11):3711-3. 
PMID: 1368866 [PubMed - indexed for MEDLINE] 

Inhibition of wheat embryo calcium-dependent protein kinase and other
kinases by mangostin and gamma-mangostin.

Jinsart W, Ternai B, Buddhasukh D, Polya GM.

Department of Chemistry, La Trobe University, Bundoora, Victoria, Australia.

The hull of the fruit of the mangosteen tree (Garcinia mangostana) contains four inhibitors of
plant Ca(2+)-dependent protein kinase. Two of these inhibitors have been purified and identified
as the xanthones 1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H- xanthen-9-one
(mangostin) and 1,3,6,7-tetrahydroxy-2,8-bis(3-methyl-2-butenyl)- 9H-xanthen-9-one
(gamma-mangostin). Both xanthones also inhibit avian myosin light chain kinase and rat liver
cyclic AMP-dependent protein kinase. This is the first report of inhibition of plant and animal |
second messenger-regulated protein kinases by plant-derived xanthones.

PMID: 1368866 [PubMed - indexed for MEDLINE]
 21:  Sundaram BM, Gopalakrishnan C, Subramanian S, Shankaranarayanan D, Kameswaran L.
 Antimicrobial activities of Garcinia mangostana.
Planta Med. 1983 May;48(1):59-60. No abstract available.
PMID: 6611746 [PubMed - indexed for MEDLINE]

Antimicrobial activities of Garcinia mangostana.

Sundaram BM, Gopalakrishnan C, Subramanian S, Shankaranarayanan D, Kameswaran L.

PMID: 6611746 [PubMed - indexed for MEDLINE]  
22:  Gopalakrishnan C, Shankaranarayanan D, Kameswaran L, Nazimudeen SK.
 Effect of mangostin, a xanthone from Garcinia mangostana Linn. in
immunopathological & inflammatory reactions.
Indian J Exp Biol. 1980 Aug;18(8):843-6. No abstract available.
PMID: 7461736 [PubMed - indexed for MEDLINE] 

Effect of mangostin, a xanthone from 
Garcinia mangostana Linn. in immunopathological 
& inflammatory reactions.

Gopalakrishnan C, Shankaranarayanan D, Kameswaran L, Nazimudeen SK.

PMID: 7461736 [PubMed - indexed for MEDLINE]
23:  Shankaranarayan D, Gopalakrishnan C, Kameswaran L. 
 Pharmacological profile of mangostin and its derivatives.
Arch Int Pharmacodyn Ther. 1979 Jun;239(2):257-69.
PMID: 314790 [PubMed - indexed for MEDLINE]

 Pharmacological profile of mangostin and its derivatives.

Shankaranarayan D, Gopalakrishnan C, Kameswaran L.

Mangostin (M), a naturally occurring xanthone in the rinds of the fruits of
Garcinia mangostana Linn. (Guttiferae) and its derivatives such as
3-0-methyl mangostin (MM), 3,6-di-O-methyl mangostin (DM),
1-isomangostin (IM), mangostin triacetate (MT), mangostin 3,6-di-O-(tetra acetyl)
glucoside (MTG) and mangostin-6,6-di-O-glucoside (MOG) were screened for
various pharmacological effects in experimental animals...
M, IM and MT produced pronounced antiinflammatory activity both by intraperitoneal
and oral routes in rats as tested by carrageenininduced hind paw
oedema, cotton pellet implantation and granuloma pouch techniques. Antiinflammatory activity
for M, IM and MT was observed even in bilaterally adrenalectomised rats. M, IM and MT
did not produce any mast cell membrane stabilising effect and the degranulation effect of
polymyxin B, diazoxide and Triton X-100 on rat peritoneal mast cells in vitro was not
prevented. M, IM and MT did not alter the prothrombin time of albino rats. M alone produced significant antiulcer activity in rats.

PMID: 314790 [PubMed - indexed for MEDLINE]   

*Antiproliferation, *antioxidation and induction of *apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line

Primchanien Moongkarndi^{, , a}, Nuttavut Kosem^a, Sineenart Kaslungka^b, Omboon Luanratana^c, Narongchai Pongpan^c and Neelobol Neungton^d

epartment of Microbiology, Faculty of Pharmacy, Mahidol University, Sri Ayudthaya Road, Rajdhevee, Bangkok 10400, Thailand
The Government Pharmaceutical Organization, Rama VI Road, Bangkok 10400, Thailand
Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Sri Ayudthaya Road, Rajdhevee, Bangkok 10400, Thailand
Department of Biochemistry, Faculty of Medicine, Siriraj Hospital, Bangkok 10700, Thailand

Received 15 June 2002;  revised 10 September 2003;  accepted 22 September 2003. ; Available online 5 December 2003.

The only product on the market today which includes all the Xanthones derived from the
Mangosteen Fruit Pruee of SouthEast Asia (41 have been identified to date) is XANGO.