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Gamma-Mangostin Xanthone acts an Anti-
Inflammatory


1: Mol Pharmacol. 2004 Jun 24 [Epub ahead of print] Related Articles, Links. Gamma-Mangostin Inhibits IkappaB Kinase Activity and Decreases Lipopolysaccharide-Induced Cyclooxygenase-2 Gene Expression in C6 Rat Glioma Cells. Nakatani K, Yamakuni T, Kondo N, Arakawa T, Oosawa K, Shimura S, Inoue H, Ohizumi Y. Graduate school of Pharmaceutical Science, Tohoku University. 
PMID: 15218091 [PubMed - as supplied by publisher]
mangosteen-01We here investigated the effect of gamma-mangostin purified from the fruit hull of the medicinal plant, Garcinia mangostana, on spontaneous prostaglandin E2 (PGE2) release and inducible cyclooxygenase (COX-2) gene expression in C6 rat glioma cells.

An 18-h treatment with gammamangostin potently inhibited spontaneous PGE2 release in a concentration-dependent manner with the IC50 value of about 2 microM, without affecting the cell viability even at 30 microM.

By immunoblotting and RT-PCR, it was shown that gamma-mangostin concentration-dependently inhibited lipopolysaccharide (LPS)-induced expression of COX-2 protein and its mRNA, but not those of constitutive COX-1 cyclooxygenase.

Since LPS is known to stimulate IkappaB kinase (IKK)-mediated phosphorylation of inhibitor kappaB (IkappaB) followed by its degradation which in turn induces NF-kappaB nuclear translocation leading to transcriptional activation of COX-2 gene, the effect of gamma-mangostin on the IKK/IkappaB cascade controlling the NF-kappaB activation was examined.

An in vitro IKK assay using IKK protein immunoprecipitated from C6 cell extract showed that this compound inhibited IKK activity in a concentration-dependent manner with the IC50 value of about 10 microM. Consistently gamma-mangostin was also observed to decrease the LPS-induced IkappaB degradation and phosphorylation in a concentrationdependent manner, as assayed by immunoblotting.

Furthermore, luciferase reporter assays showed that gamma-mangostin reduced the LPS-inducible activation of NF-kappaB- and human COX-2 gene promoter region-dependent transcription. gamma-Mangostin also inhibited rat carrageenan-induced paw edema.

These results suggest that gamma-mangostin directly inhibits IKK activity, and thereby prevents COX-2 gene transcription, an NF-kappaB target gene, probably to decrease the inflammatory agent-stimulated PGE2 production in vivo, and is a new useful lead compound for anti-inflammatory drug development.
Disclaimer
The Xanthones from the mangosteen have been shown in laboratory studies to be powerful Antioxidants, Anti-Inflammatories and to have other special properties. However, laboratory results do not guarantee that the same will happen in the human body. Mangosteen is a nutritious fruit not a drug, and no therapeutic claims are made for this product.