Nuclear Factor-κB/Signal Transducers and Activators of Transcription-1-Mediated Inflammatory Responses in Lipopolysaccharide-Activated Macrophages Are a Major Inhibitory Target of Kahweol, a Coffee Diterpene

• Published in: Biological & pharmaceutical bulletin Vol. 33; no. 7; pp. 1159 - 1164
• Main Authors: Shen, Ting, Park, Yung Chul, Kim, Seong Hwan, Lee, Jaehwi, Cho, Jae Youl
• Format: Journal Article
• Language: English
• Published: The Pharmaceutical Society of Japan 01.07.2010
• Subjects: AKT protein; coffee diterpene; kahweol; nitric oxide; nuclear factor-κB; prostaglandin E2; signal transducer and activator of transcription-1
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.33.1159

Diterpene kahweol, one of the major components in coffee, has anti-cancer, anti-oxidative, and anti-inflammatory activity. In this study, we explored the molecular mechanism of the anti-inflammatory activity of kahweol. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore the modulatory role of kahweol on nitric oxide (NO) and prostaglandin E2 (PGE2) production and the activation of signaling proteins and transcription factors using immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). Kahweol diminished both the production of NO and PGE2 and the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, this compound suppressed the phospho-signal transducers and activators of transcription (STAT)-1 and p65/nuclear factor (NF)-κB levels in the nucleus but not c-Jun and c-fos. In conjunction, the phosphorylation of Akt and Janus kinase (JAK)2 also decreased. Therefore, our data suggest that kahweol in coffee may be an anti-inflammatory modulator with NF-κB/STAT-1-targeted inhibitory properties in LPS-activated RAW264.7 cells.