Garcinone B reduces prostaglandin E2 release and NF-kappaB-mediated transcription in C6 rat glioma cells.

Abstract

In the course of our survey of natural compounds inhibiting prostaglandin E2 release and/or lipopolysaccharide (LPS)-induced transcriptional stimulation via NF-kappaB, a central regulator of inflammatory genes, from natural resources, we found garcinone B, a xanthone from callus tissue culture of Hypericum patulum, as a compound with such pharmacological activities, that is a derivative of gamma-mangostin which potently inhibits COX-1 and COX-2 activities to reduce PGE2 release from C6 rat glioma cells, and inhibits IKK activity to prevent NF-kappaB-dependent COX-2 gene transcription. Garcinone B, to a lesser extent, reduced A23187-induced increase in prostaglandin E2 release than gamma-mangostin and its structurally related compound, patulone, in C6 cells. This compound also prevented LPS-induced stimulation of NF-kappaB-dependent transcription. These results suggest that garcinone B becomes a unique pharmacological tool to investigate intracellular signaling pathways involved in inflammation.

• Authors: Tohru Yamakuni, Koichi Aoki, Keigo Nakatani, Nobuhiko Kondo, Hisae Oku, Kyoko Ishiguro, Yasushi Ohizumi
• Journal: Neuroscience letters (Neurosci Lett) Vol. 394 Issue 3 Pg. 206-10 (Feb 20 2006) ISSN: 0304-3940 [Print] Ireland
• PMID: 16260090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Garcinone B
• Inflammation Mediators
• Lipopolysaccharides
• NF-kappa B
• Prostaglandin Antagonists
• Xanthines
• Xanthones
• Calcimycin
• Cyclooxygenase 1
• Dinoprostone
• mangostin

Topics

• Animals
• Brain Neoplasms (metabolism)
• Calcimycin (pharmacology)
• Cell Line, Tumor
• Cyclooxygenase 1 (metabolism)
• Dinoprostone (metabolism)
• Glioma (metabolism)
• Hypericum (chemistry)
• Inflammation Mediators (metabolism)
• Lipopolysaccharides (pharmacology)
• NF-kappa B (genetics)
• Prostaglandin Antagonists (pharmacology)
• Rats
• Transcription, Genetic (drug effects)
• Xanthines (pharmacology)
• Xanthones (pharmacology)