PhytoScience - Science 
Anti-inflammatory - Invivo
gamma-Mangostin inhibits inhibitor-kappaB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells.
1: Mol Pharmacol. 2004 Jun 24 [Epub ahead of print]
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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.
We here investigated the effect of gamma-mangostin purified from the fruit hull of the medicinal plant, Garcinia mangostana, on pontaneous 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.
PMID: 15322259 [PubMed - indexed for MEDLINE]
PMID: 15218091 [PubMed - as supplied by publisher]
Anti-inflammatory - Invivo
Inhibition of cyclooxygenase and prostaglandin E2 synthesis by gamma-mangostin, a xanthone derivative in mangosteen, in C6 rat glioma cells.
1: Biochem Pharmacol. 2002 Jan 1;63(1):73-9
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, gammamangostin
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]
Anti-inflammatory - Invivo
Anti-inflammatory activity of mangostins from Garcinia mangostana
Chen LG, Yang LL, Wang CC.
Graduate Institute of Biomedical and Biopharmaceutical Sciences, College of Life Sciences, National Chiayi University, 300 University Road, Chiayi 600, Taiwan, ROC.
The fruit hull of Garcinia mangostana Linn (Guttiferae) is used as an anti-inflammatory drug in Southeast Asia.
Two xanthones, alpha- and gamma-mangostins, were isolated from the fruit hull of G. mangostana, and both significantly inhibited nitric oxide (NO) and PGE(2) production from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The IC(50) values for the inhibition of NO production by alpha- and gamma-mangostins were 12.4 and 10.1muM, respectively.
After iNOS enzyme activity was stimulated by LPS for 12h, treatment with either alpha- or gamma-mangostin at 5mug/ml (12.2 and 12.6muM, respectively) for 24h did not significantly inhibit NO production.
The data shows that the inhibitory activities of alpha- and gamma-mangostins are not due to direct inhibition of iNOS enzyme activity. On the other hand, expression of iNOS was inhibited by alpha- and gamma-mangostins in LPS-stimulated RAW 264.7 cells, but not by COX-2. However, the level of PGE(2) production was reduced by the two xanthones.
In an in vivo study, alpha-mangostin significantly inhibited mice carrageenan-induced paw edema. In conclusion, alpha- and gamma-mangostins from G. mangostana are bioactive substances with anti-inflammatory effects.
PMID: 18029076 [PubMed - in process]
Anti-inflammatory - Invivo
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.
With the exception of DM all the test compounds produced CNS depression characterised by ptosis, sedation, decreased motor activity, potentiation of pentobarbital sleeping time and ether anaesthesia in mice and rats.
None of the compounds exhibited analgesic, antipyretic and anticonvulsant effects. With the exception of MOG, none of the test compounds produced significant effects on the cardiovascular system of frogs and dogs.
MOG produced myocardial stimulation and a rise in blood pressure which was partially blocked by propranolol. 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]