Garcinone B reduces prostaglandin E2 release and NF-kappaB-mediated transcription in C6 rat glioma cells.
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.
Yamakuni
Tohru
T
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Aoki
Koichi
K
Nakatani
Keigo
K
Kondo
Nobuhiko
N
Oku
Hisae
H
Ishiguro
Kyoko
K
Ohizumi
Yasushi
Y
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D020902:Hypericum / Q000737:chemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology*
C509049:Garcinone B; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011448:Prostaglandin Antagonists; D014970:Xanthines; D044004:Xanthones; D000001:Calcimycin; D051545:Cyclooxygenase 1; D015232:Dinoprostone; C021053:mangostin