Effects of yakuchinone A and yakuchinone B on the phorbol ester-induced expression of COX-2 and iNOS and activation of NF-kappaB in mouse skin.
Certain medicinal plants contain anti-inflammatory and antioxidative substances that can exert chemopreventive effects. Our previous studies have demonstrated that the methanol extract of Alpinia oxyphylla Miquel (Zingiberaceae) inhibits tumor promotion in mouse skin. Two major diarylheptanoids named yakuchinone A (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenyl-3-heptanone) andyakuchinone B (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenylhept-1-en-3-one) have been isolated from this medicinal plant. Both compounds have strong inhibitory effects on the synthesis of prostaglandins and leukotrienes in vitro. In the present work, we show that both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
Chun
Kyung-Soo
KS
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, South Korea.
Kang
Jee-Young
JY
Kim
Ok Hee
OH
Kang
Hoil
H
Surh
Young-Joon
YJ
D000287:Administration, Topical; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D036381:Diarylheptanoids; D015536:Down-Regulation; D005260:Female; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000096:biosynthesis / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012867:Skin; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D002316:Cardiotonic Agents; D036381:Diarylheptanoids; D007527:Isoenzymes; D016328:NF-kappa B; D010703:Phorbol Esters; D014409:Tumor Necrosis Factor-alpha; C121978:yakuchinone B; D006139:Guaiacol; C042566:yakuchinone-A; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases