The coffee diterpene kahweol suppress the inducible nitric oxide synthase expression in macrophages.
Excessive nitric oxide production by inducible nitric oxide synthase (iNOS) in stimulated inflammatory cells is thought to be a causative factor of cellular injury in cases of inflammation. In recent studies, it has been shown that kahweol, coffee-specific diterpene, exhibit chemoprotective effects. In this study, we investigated the effects of kahweol on the production of and the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The nitrite production induced by LPS was markedly reduced in a dose-dependent manner. In addition, kahweol suppressed the expression of iNOS protein and iNOS mRNA. Since iNOS transcription has been shown to be under the control of the transcription factor, NF-kappaB, the effects of kahweol on NF-kappaB activation were examined. Transient transfection experiments showed that kahweol inhibited NF-kappaB-dependent transcriptional activity. Moreover, electrophoretic mobility shift assay experiments indicated that kahweol blocked the LPS-induced activation of NF-kappaB. The results of these studies suggest that the suppression of the transcriptional activation of iNOS by kahweol might be mediated through the inhibition of NF-kappaB activation. Taken together, the results of our study provide evidence that kahweol possess an anti-inflammatory potential, which constitutes a previously unrecognized biologic activity, and which may provide new insights into the inflammatory process.
Kim
Ji Young
JY
Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju, South Korea.
Jung
Kyung Sik
KS
Lee
Kyung Jin
KJ
Na
Han Kwang
HK
Chun
Hyo-Kon
HK
Kho
Yung-Hee
YH
Jeong
Hye Gwang
HG
D000818:Animals; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007249:Inflammation; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects
D004224:Diterpenes; C053401:kahweol; D019001:Nitric Oxide Synthase