Institut für Mangostan & natürliche Antioxidantien

Institut für Mangostan & natürliche Antioxidantien

Wissenschaftliche Studien und internationale Forschungsergebnisse | 56-75

56: Biol Pharm Bull. 2002 Sep;25(9):1137-41.
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Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen, a Thai medicinal plant.

Nakatani K, Atsumi M, Arakawa T, Oosawa K, Shimura S, Nakahata N, Ohizumi Y.

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

The fruit hull of mangosteen, Garcinia mangostana L. has been used as a Thai indigenous medicine for many years. However, its mechanism of action as a medicine has not been elucidated. The present study was undertaken to examine the effects of mangosteen extracts (100% ethanol, 70% ethanol, 40% ethanol and water) on histamine release and prostaglandin E2 synthesis. We found that the 40% ethanol extract of mangosteen inhibited IgE-mediated histamine release from RBL-2H3 cells with greater potency than the water extract of Rubus suavissimus that has been used as an anti-allergy crude drug in Japan. All extracts of mangosteen potently inhibited A23187-induced prostaglandin E2 synthesis in C6 rat glioma cells, while the water extract of Rubus suavissimus had no effect. The 40% ethanol extract of mangosteen inhibited the prostaglandin E2 synthesis in a concentration-dependent manner with relatively lower concentrations than the histamine release. In addition, passive cutaneous anaphylaxis (PCA) reactions in rats were significantly inhibited by this ethanol extract as well as by the water extract of Rubus suavissimus. These results suggest that the 40% ethanol extract of mangosteen has potent inhibitory activities of both histamine release and prostaglandin E2 synthesis.

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PMID: 12230104 [PubMed - indexed for MEDLINE]

57: Phytochemistry. 2002 Jul;60(5):541-8.
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Xanthones from the heartwood of Garcinia mangostana.

Nilar , Harrison LJ.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.

Twelve xanthones were isolated from the hexane extract of the heartwood of Garcinia mangostana from Myanmar. Their structures were determined using 1D and 2D NMR techniques

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PMID: 12052521 [PubMed - indexed for MEDLINE]

58: J Nat Prod. 2002 May;65(5):761-3.
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Xanthones from the green fruit hulls of Garcinia mangostana.

Suksamrarn S, Suwannapoch N, Ratananukul P, Aroonlerk N, Suksamrarn A.

Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.

Three new xanthones, mangostenol (1), mangostenone A (2), and mangostenone B (3), were isolated from the green fruit hulls of Garcinia mangostana, along with the known xanthones, trapezifolixanthone, tovophyllin B (4), alpha- and beta-mangostins, garcinone B, mangostinone, mangostanol, and the flavonoid epicatechin. The structures of the new xanthones were elucidated by analysis of their spectroscopic data.

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PMID: 12027762 [PubMed - indexed for MEDLINE]

59: J Med Assoc Thai. 2001 Dec;84(12):1751-3.
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Sigmoid colon perforation by ingested Sandorica seed.

Somboonpanya P.

Department of Surgery, Prachomklao Hospital, Phetchaburi, Thailand.

This retrospective descriptive study of Sigmoid colon perforation by ingested Sandorica seed in patients who were admitted to Prachomklao Hospital from 1996 to 2000. Nine cases were included in this study. Most cases were elderly with a mean age of 65 years (range 52-78 years). The main symptoms were abdominal pain with generalized peritonitis and severe tenderness at the suprapubic area, ileus and persistent vomiting. In all cases, the diagnosis was made at operation, with removal of the Sandorica seed, closure of the perforation at the rectosigmoid colon with simple suture and proximal transverse loop colostomy. Post-operative complications included two cases of wound infection.

PMID: 11999823 [PubMed - indexed for MEDLINE]

60: Biochem Pharmacol. 2002 Jan 1;63(1):73-9.
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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.

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PMID: 11754876 [PubMed - indexed for MEDLINE]

61: J Nat Prod. 2001 Jul;64(7):903-6.
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Three xanthones and a benzophenone from Garcinia mangostana.

Huang YL, Chen CC, Chen YJ, Huang RL, Shieh BJ.

National Research Institute of Chinese Medicine, No. 155-1, Sec. 2, Li Nung Street Peitou, Taipei, Taiwan, Republic of China.

Investigation of the constituents of Garcinia mangostana has led to the isolation of four new compounds: three minor xanthones, garcimangosone A (1), garcimangosone B (2), and garcimangosone C (3), and a benzophenone glucoside, garcimangosone D (4). The structures of these four compounds were established by spectral (NMR and MS) and chemical methods.

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PMID: 11473420 [PubMed - indexed for MEDLINE]

62: Fitoterapia. 2000 Sep;71(5):607-9.
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Two novel xanthones from Garcinia mangostana.

Gopalakrishnan G, Balaganesan B.

Centre for Natural Products SPIC Science Foundation 111, Mount Road, Chennai 600 032, India.

The isolation of two novel xanthones isolated from the fruit hulls of Garcinia mangostana is reported. The structures were elucidated by means of spectroscopic analysis.

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PMID: 11449524 [PubMed - indexed for MEDLINE]

63: Free Radic Res. 2000 Nov;33(5):643-59.
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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.

Publication Types:

PMID: 11200095 [PubMed - indexed for MEDLINE]

64: J Enzyme Inhib. 2000;15(2):129-38.
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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 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]

65: Southeast Asian J Trop Med Public Health. 1999 Sep;30(3):399-404.
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Malaria in tree crop plantations in south-eastern and western provinces of Thailand.

Singhasivanon P, Thimasarn K, Yimsamran S, Linthicum K, Nualchawee K, Dawreang D, Kongrod S, Premmanisakul N, Maneeboonyang W, Salazar N.

Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

During the past three decades almost half of the existing natural tropical forests in Thailand were destroyed and replaced by cash crops, rubber, coffee, fruit orchards (durian, rambutan, mangosteen) and other commercial plantations. In order to determine the proportion of malaria cases contracted from such commercial plantations, an epidemiological study was conducted between June 1996 to May 1997 in two districts, one in Pong Nam Ron, located in a south-eastern province near the Cambodian border and another in Sai Yok, in a western province along the Myanmar border. Data were collected by passive case detection from patients attending the existing malaria clinics and active case detection by monthly malariometric survey in selected villages. All malaria cases were thoroughly investigated and classified according to exposure to different ecotypes prior to onset of malaria symptoms in the preceding two weeks. Malaria cases acquired from commercial plantations accounted for 35.2% and 11.2% in Pong Nam Ron and in Sai Yok districts respectively. In such plantations, most of the malaria cases were contracted from fruit orchards and to a lesser extent from rubber and teak plantations. From this study it is evident that commercial plantations provide a significant site of malaria transmission in addition to the forest and foothills areas in Southeast Asia where efficient vectors such as An. dirus and An. minimus are prevalent and have adapted to such changed ecosystems.

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PMID: 10774642 [PubMed - indexed for MEDLINE]

66: Nat Biotechnol. 1999 Jun;17(6):593-7.
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Improved stearate phenotype in transgenic canola expressing a modified acyl-acyl carrier protein thioesterase.

Facciotti MT, Bertain PB, Yuan L.

Calgene, LLC, Davis, CA 95616, USA.

The engineering of crops for selected fatty acid production is one of the major goals of plant biotechnology. The Garm FatA1, an acyl-acyl carrier protein (ACP) thioesterase isolated from Garcinia mangostana, generates an elevated stearate (18:0) phenotype in transgenic Brassica plants. By site-directed mutagenesis, we generated seven mutants that showed up to a 13-fold increase in specific enzyme activity toward 18:0-ACP in vitro. The seed-specific expression of mutant S111A/V193A in Brassica plants results in transgenic plants that accumulate 55-68% more stearate than plants expressing the wild-type enzyme. Our results demonstrate that a thioesterase can be engineered to increase specific activity and that its improved function demonstrated in vitro is retained in vivo.

PMID: 10385326 [PubMed - indexed for MEDLINE]

67: Chem Biol Interact. 1998 Jul 3;114(1-2):121-40.
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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.

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PMID: 9744560 [PubMed - indexed for MEDLINE]

68: Environ Health Perspect. 1998 Sep;106(9):581-6.
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Characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model.

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

Institut für Molekulare Medizin, Medizinische Universität zu Lübeck, Lübeck, 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.

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PMID: 9721258 [PubMed - indexed for MEDLINE]
PMCID: PMC1533165

69: Plant J. 1998 Mar;13(6):743-52.
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Characterization of acyl-ACP thioesterases of mangosteen (Garcinia mangostana) seed and high levels of stearate production in transgenic canola.

Hawkins DJ, Kridl JC.

Calgene, Inc., Davis, CA 95616, USA.

Acyl-acyl-carrier protein (ACP) thioesterases are, at least in part, responsible for the fatty acyl chain length composition of seed storage oils. Acyl-ACP thioesterases with specificity for each of the saturated acyl-ACP substrates from 8:0 through 16:0 have been cloned, with the exception of 18:0, and are members of the FatB class of thioesterases. The authors have determined that the tropical tree species mangosteen (Garcinia mangostana) stores 18:0 (stearate) in its seed oil in amounts of up to 56% by weight. Acyl-ACP thioesterase activity as measured in crude mangosteen seed extracts showed a preference for 18:1-ACP substrates, but had significant activity with 18:0 relative to that with 16:0-ACP, suggesting a thioesterase might be involved in the production of stearate. Three distinct acyl-ACP thioesterases were cloned from mangosteen seed cDNA; two representative of the FatA class and one representative of the FatB class. When expressed in vitro, the enzyme encoded by one of the FatAs (Garm FatA1) while preferring 18:1-ACP showed relatively low activity with 16:0-ACP as compared to 18:0-ACP, similar to the substrate preferences shown by the crude seed extract. Expression of Garm FatA1 in Brassica seeds led to the accumulation of stearate up to 22% in seed oil. These results suggest that Garm FatA1 is at least partially responsible for determining the high stearate composition of mangosteen seed oil and that FatA as well FatB thioesterases have evolved for specialized roles.

PMID: 9681015 [PubMed - indexed for MEDLINE]

70: Br J Pharmacol. 1998 Mar;123(5):855-62.
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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.

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PMID: 9535013 [PubMed - indexed for MEDLINE]
PMCID: PMC1565246

71: Planta Med. 1998 Mar;64(2):97-109.
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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.

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.

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PMID: 9525100 [PubMed - indexed for MEDLINE]

72: Nippon Yakurigaku Zasshi. 1997 Oct;110 Suppl 1:153P-158P.
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[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.

Publication Types:

PMID: 9503424 [PubMed - indexed for MEDLINE]

73: Planta Med. 1998 Feb;64(1):70-2.
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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:

PMID: 9491769 [PubMed - indexed for MEDLINE]

74: Naunyn Schmiedebergs Arch Pharmacol. 1998 Jan;357(1):25-31.
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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.

Publication Types:

PMID: 9459569 [PubMed - indexed for MEDLINE]

75: J Med Assoc Thai. 1997 Sep;80 Suppl 1:S149-54.
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Immunopharmacological activity of polysaccharide from the pericarb of mangosteen garcinia: phagocytic intracellular killing activities.

Chanarat P, Chanarat N, Fujihara M, Nagumo T.

Department of Clinical Microscopy, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand.

Polysaccharides from the pericarbs of mangosteen, Garcinia mangostana Linn., was obtained by treating the dried ground pericarbs with hot water followed by ethanol precipitation (M fraction). The extract was fractionated by anion exchange chromatography on a DEAE-cellulose column as MDE1-5 fractions. The fractions of MDE3 and MDE4 composed of mainly D-galacturonic acid and a small amount of neutral sugar (L-arabinose as the major one and L-rhamnose and D-galactose as the minor ones) were studied for immunopharmacological activities by phagocytic test to intracellular bacteria (Salmonella enteritidis) and nitroblue tetrazolium (NBT) and superoxide generation tests. The results showed that the number of S. enteritidis in cultured monocyte with extract of pericarb of mangosteen (MDE3) was killed. Activating score (mean +/- SD) of NBT test of 100 polymorphonuclear phagocytic cells were 145 +/- 78, 338 +/- 58, 222 +/- 73, 209 +/- 77, 211 +/- 63, 372 +/- 19, 369 +/- 20, 355 +/- 34 in normal saline control, phorbol myristate acetate (PMA), MDE3, MDE4, indomethacin (I), PMA + MDE3, PMA + MDE4 and PMA + I, respectively. Superoxide generation test was also done by color reduction of cytochrome c. Both MDE3 and MDE4 stimulate superoxide production. The number of S. enteritidis in cultured monocyte with extract of pericarb of mangosteen was killed. This paper suggests that polysaccharides in the extract can stimulate phagocytic cells and kill intracellular bacteria (S. enteritidis).

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PMID: 9347663 [PubMed - indexed for MEDLINE]


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