Beta-mangostin

J Ethnopharmacol. 2014 Apr 28;153(2):435-45.

β Mangostin suppress LPS-induced inflammatory response in RAW 264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo.[Pubmed: 24607509]

The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.
METHODS AND RESULTS:
The in silico analysis of inflammatory mediators such as cyclooxygenase (COX) and nuclear factor-kappa B (NF-kB) were performed via molecular docking. Further evaluation of anti-inflammatory effect was conducted in lipopolysaccharide (LPS) induced RAW 264.7 macrophages. Suppression of activated NF-kB was analyzed by high content screening. βM triggered inhibition of COX-1 and COX-2 in vitro were studied using biochemical kit. The in vivo model used in this study was carrageenan-induced peritonitis model, where reduction in carrageenan-induced peritonitis is measured by leukocyte migration and vascular permeability. In addition, the evaluation of βM׳s effect on carrageenan induced TNF-α and IL-1β release on peritoneal fluid was also carried out. Treatment with βM could inhibit the LPS-induced NO production but not the viability of RAW 264.7. Similarly, βM inhibited PGE2 production and the cytokines: TNF-α and IL-6. The COX catalyzed prostaglandin biosynthesis assay had showed selective COX-2 inhibition with a 53.0±6.01% inhibition at 20 μg/ml. Apart from this, βM was capable in repressing translocation of NF-kB into the nucleus. These results were concurrent with molecular docking which revealed COX-2 selectivity and NF-kB inhibition. The in vivo analysis showed that after four hours of peritonitis, βM was unable to reduce vascular permeability, yet could decrease the total leukocyte migration; particularly, neutrophils. Meanwhile, dexamethasone 0.5 mg/kg, successfully reduced vascular permeability. The levels of TNF-α and IL-1β in peritoneal fluid was reduced significantly by βM treatment.
CONCLUSIONS:
The current study supports the traditional use of Garcinia mangostana fruit hull for treatment of inflammatory conditions. In addition, it is clear that the anti-inflammatory efficacy of this plant is not limited to the presence of α and γ, but β also with significant activity.

Fitoterapia. 2014 Oct;98:179-83.

Antibacterial tetraoxygenated xanthones from the immature fruits of Garcinia cowa.[Pubmed: 25110196]

METHODS AND RESULTS:
A phytochemical investigation of the acetone extract from the immature fruits of Garcinia cowa led to the isolation of two novel tetraoxygenated xanthones, garcicowanones A (1) and B (2), together with eight known tetraoxygeanted xanthones. Their structures were determined by spectroscopic analysis.All isolated compounds were evaluated for their antibacterial activity against Bacillus cereus TISTR 688, Bacillus subtilis TISTR 008, Micrococcus luteus TISTR 884, Staphylococcus aureus TISTR 1466, Escherichia coli TISTR 780, Pseudomonas aeruginosa TISTR 781, Salmonella typhimurium TISTR 292 and Staphylococcus epidermidis ATCC 12228.
CONCLUSIONS:
α-Mangostin showed potent activity (MIC 0.25-1 μg/mL) against three Gram-positive strains and garcicowanone A and Beta-mangostin exhibited strong antibacterial activity against B. cereus with the same MIC values of 0.25 μg/mL.

Tumour Biol . 2017 Nov;39(11):1010428317731451.

Beta-mangostin from Cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G 0/G 1 cell-cycle arrest[Pubmed: 29110583]

Abstract Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by Beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 μM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G0/G1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G0/G1 phase and prompted the intrinsic apoptosis pathway. Keywords: Apoptosis; HL60 cell line; Beta-mangostin; intrinsic pathway; leukemia; xanthones.

Environ Toxicol . 2017 Nov;32(11):2360-2370.

β-mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP-2 and MMP-9 expression and activating the ERK and JNK pathways[Pubmed: 28722351]

Abstract β-mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of β-mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that β-mangostin did not induce cytotoxicity in human HCC cells (SK-Hep-1, Huh-7 and HA22T/VGH cells). β-mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, β-mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP-2/-9 and invasion by β-mangostin treatment in Huh-7 cells. In addition, β-mangostin effectively restored the protein levels and transcription activity of MMP-2 and MMP-9 in siERK or siJNK-transfected Huh-7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of β-mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC. Keywords: MMP-2; MMP-9; hepatocellular carcinoma cell; invasion; migration; β-Mangostin.

Planta Med. 2014 Jun;80(8-9):676-81.

In vitro antiplasmodial activity of benzophenones and xanthones from edible fruits of Garcinia species.[Pubmed: 24963617]

Species of Garcinia have been used to combat malaria in traditional African and Asian medicines, including Ayurveda.
METHODS AND RESULTS:
In the current study, we have identified antiplasmodial benzophenone and xanthone compounds from edible Garcinia species by testing for in vitro inhibitory activity against Plasmodium falciparum. Whole fruits of Garcinia xanthochymus, G. mangostana, G. spicata, and G. livingstonei were extracted and tested for antiplasmodial activity. Garcinia xanthochymus was subjected to bioactivity-guided fractionation to identify active partitions. Purified benzophenones (1-9) and xanthones (10-18) were then screened in the plasmodial lactate dehydrogenase assay and tested for cytotoxicity against mammalian (Vero) cells. The benzophenones guttiferone E (4), isoxanthochymol (5), and guttiferone H (6), isolated from G. xanthochymus, and the xanthones α-mangostin (15), β-mangostin (16), and 3-isomangostin (17), known from G. mangostana, showed antiplasmodial activity with IC50 values in the range of 4.71-11.40 μM. Artemisinin and chloroquine were used as positive controls and exhibited IC50 values in the range of 0.01-0.24 μM.
CONCLUSIONS:
The identification of antiplasmodial benzophenone and xanthone compounds from G. xanthochymus and G. mangostana provides evidence for the antiplasmodial activity of Garcinia species and warrants further investigation of these fruits as dietary sources of chemopreventive compounds.

Chem Pharm Bull (Tokyo). 2006 May;54(5):745-7.

Cytotoxic and antimalarial prenylated xanthones from Cratoxylum cochinchinense.[Pubmed: 16651783]

METHODS AND RESULTS:
A new prenylated xanthone, 5-O-methylcelebixanthone (1), together with six known compounds; celebixanthone (2), 1,3,7-trihydroxy-2,4-di(3-methylbut-2-enyl)xanthone (3), cochinchinone A (4), alpha-mangostin (5), Beta-mangostin (6) and cochinchinone C (7) were isolated from roots of Cratoxylum cochinchinense. Their structures were elucidated by spectroscopic methods.
CONCLUSIONS:
Compounds 2 and 4-7 showed cytotoxic activity against the human lung cancer cell line (NCI-H187) with IC(50) values ranging from 0.65 to 5.2 microg/ml. Compounds 1, 2, 6 and 7 also showed antimalarial activity against Plasmodium falciparum with IC(50) values of 3.2, 4.9, 7.2 and 2.6 microg/ml, respectively.

Chem Pharm Bull (Tokyo). 2003 Jul;51(7):857-9.

Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia mangostana.[Pubmed: 12843596]

METHODS AND RESULTS:
Prenylated xanthones, isolated from the fruit hulls and the edible arils and seeds of Garcinia mangostana, were tested for their antituberculosis potential. Alpha- and Beta-mangostins and garcinone B exhibited strong inhibitory effect against Mycobacterium tuberculosis with the minimum inhibitory concentration (MIC) value of 6.25 microg/ml. Tri- and tetra-oxygenated xanthones with di-C5 units or with a C5 and a modified C5 groups are essential for high activities.
CONCLUSIONS:
Substitution in the A and C rings has been shown to modify the bioactivity of the compounds.