Mangostenone F

Anti-Inflammatory Effect of Mangostenone F in Lipopolysaccharide-Stimulated RAW264.7 Macrophages by Suppressing NF-kappaB and MAPK Activation.[Pubmed:25143806]

Biomol Ther (Seoul). 2014 Jul;22(4):288-94.

Mangostenone F (MF) is a natural xanthone isolated from Garcinia mangostana. However, little is known about the biological activities of MF. This study was designed to investigate the anti-inflammatory effect and underlying molecular mechanisms of MF in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. MF dose-dependently inhibited the production of NO, iNOS, and pro-inflammatory cytokines (TNF-alpha, IL-6, and IL-1beta) in LPS-stimulated RAW264.7 macrophages. Moreover, MF decreased the NF-kappaB luciferase activity and NF-kappaB DNA binding capacity in LPS-stimulated RAW264.7 macrophages. Furthermore, MF suppressed the NF-kappaB activation by inhibiting the degradation of IkappaBalpha and nuclear translocation of p65 subunit of NF-kappaB. In addition, MF attenuated the AP-1 luciferase activity and phosphorylation of ERK, JNK, and p38 MAP kinases. Taken together, these results suggest that the anti-inflammatory effect of MF is associated with the suppression of NO production and iNOS expression through the down-regulation of NF-kappaB activation and MAPK signaling pathway in LPS-stimulated RAW264.7 macrophages.

Inhibition effects of mangosenone F from Garcinia mangostana on melanin formation in B16F10 cells.[Pubmed:22779928]

J Agric Food Chem. 2012 Aug 29;60(34):8372-8.

Melanogenesis can be controlled by tyrosinase inhibition or by blocking the maturation processes of tyrosinase and its related proteins. Mangostenone F was isolated from the seedcases of Garcinia mangostana . Mangostenone F was shown to be inactive against tyrosinase (IC50 > 200 muM) but was a potent alpha-glucosidase inhibitor in vitro (IC50 = 21.0 muM). Mangostenone F was found to inhibit production of melanin in the mouse melanoma cell line B16F10. Importantly, unlike most glycosidase inhibitors, Mangostenone F displayed very low cytotoxicity (EC50 > 200 muM). The Western blot for expression levels of proteins involved in melanogenesis showed that Mangostenone F down-regulated tyrosinase and TRP-2 expression. Treating B16F10 cells with Mangostenone F significantly increased the susceptibility of tyrosinase to endoglycosidase H digestion, indicating that tyrosinase was unable to mature fully and pass to the trans-golgi apparatus. Consistent with these data, in lysate assays, Mangostenone F was shown to be a better inhibitor of alpha-glucosidases than deoxynojirimycin, a representative glycosidase inhibitor.

Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia mangostana.[Pubmed:20696581]

Bioorg Med Chem. 2010 Sep 1;18(17):6258-64.

This study was designed to gain deeper insights into the molecular properties of natural xanthones as neuraminidase inhibitors. A series of xanthones 1-12 was isolated from the seedcases of Garcinia mangostana and evaluated for bacteria neuraminidase inhibitory activity. Compounds 11 and 12 emerged to be new xanthones (Mangostenone F, mangostenone G) which we fully spectroscopically characterized. The IC(50) values of compounds 1-12 were determined to range between 0.27-65.7 microM. The most potent neuraminidase inhibitor 10 which has an IC(50) of 270 nM features a 5,8-diol moiety on the B ring. Interestingly, structure-activity studies reveal that these xanthones show different kinetic inhibition mechanisms depending upon the arrangement of hydroxyl groups in the B ring. Compound 6 possessing a 6,7-diol motif on the B-ring operated under the enzyme isomerization model (k(5)=0.1144 microM(-1) s(-1), k(6)=0.001105 s(-1), and K(i)(app)=7.41 microM), whereas compound 10 possessing a 5,8-diol unit displayed simple reversible slow-binding inhibition (k(3)=0.02294 microM(-1) s(-1), k(4)=0.001025 s(-1), and K(i)(app)=0.04468 microM).