Participation of epoxygenase activation in saikogenin D-induced inhibition of prostaglandin E(2) synthesis.

Abstract

We examined the effect of saikogenin D on arachidonic acid metabolism in C6 rat glioma cells to clarify its anti-inflammatory mechanism. Incubation of C6 cells with saikogenin D for 20 min resulted in the inhibition of prostaglandin E(2) production and the accumulation of an arachidonic acid metabolite that was found to be 11,12-dihydroxyeicosatrienoic acid, a metabolite of 11,12-epoxyeicosatrienoic acid. C6 cells expressed rat epoxygenase mRNAs, CYP1A1, CYP2B1 and CYP2J3, which converted arachidonic acid to epoxyeicosatrienoic acids. 11,12-Epoxyeicosatrienoic acid inhibited A23187-induced prostaglandin E(2) production and SKF-525A, an inhibitor of epoxygenase, attenuated the saikogenin D-induced inhibition of prostaglandin E(2) production in C6 cells. Furthermore, 11,12-epoxyeicosatrienoic acid and 11,12-dihydroxyeicosatrienoic acid, but not saikogenin D, inhibited the activity of cyclooxygenase in a cell-free condition. These data suggest that saikogenin D activates epoxygenases that rapidly convert arachidonic acid to epoxyeicosanoids and dihydroxyeicosatrienoic acids, and then the metabolites secondarily inhibit prostaglandin E(2) production.

• Authors: Yasufumi Toriniwa, Xiaochuan Lv, Yasuo Kodama, Yasushi Ohizumi, Makoto Yoshida, Norimichi Nakahata
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 58 Issue 6 Pg. 859-66 (Jun 2006) ISSN: 0022-3573 [Print] England
• PMID: 16734988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• RNA, Messenger
• Arachidonic Acid
• saikogenin A
• 11,12-epoxy-5,8,14-eicosatrienoic acid
• Oleanolic Acid
• Cytochrome P-450 Enzyme System
• Proadifen
• Oxygenases
• Cyp2j3 protein, rat
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP2B1
• Prostaglandin-Endoperoxide Synthases
• 8,11,14-Eicosatrienoic Acid
• Dinoprostone

Topics

• 8,11,14-Eicosatrienoic Acid (analogs & derivatives, pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Arachidonic Acid (metabolism)
• Cell Line, Tumor
• Cytochrome P-450 CYP1A1 (genetics, physiology)
• Cytochrome P-450 CYP2B1 (genetics, physiology)
• Cytochrome P-450 Enzyme System (genetics, physiology)
• Dinoprostone (biosynthesis)
• Enzyme Activation (drug effects)
• Oleanolic Acid (analogs & derivatives, pharmacology)
• Oxygenases (genetics, physiology)
• Proadifen (pharmacology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• RNA, Messenger (analysis)
• Rats