Y. Shiao, Yun-Lian Lin, Ya-Hui Sun
Jan 1, 2005
Citations
4
Influential Citations
21
Citations
Quality indicators
Journal
British Journal of Pharmacology
Abstract
1 The effects of falcarindiol on the expression of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide/interferon‐γ (LPS/IFN‐γ) in rat primary astrocytes were investigated. The molecular mechanisms underlying falcarindiol that confers its effect on iNOS expression were also elucidated. 2 Falcarindiol abrogated the LPS/IFN‐γ‐mediated induction of iNOS by about 80%. Falcarindiol attenuated the induction of iNOS in a concentration‐dependent manner. 3 The inhibitory effect of falcarindiol on iNOS induction was attributable to decrease in the protein content and the mRNA level of iNOS. 4 Treatment with 50 μM of falcarindiol for 30 min decreased LPS/IFN‐γ‐induced nuclear factor‐κB (NF‐κB) activation by 32%. 5 Treatment with 50 μM of falcarindiol for 60 min diminished the LPS/IFN‐γ‐mediated activation of IκB kinase‐α (IKK‐α) and IKK‐β by 28.2 and 29.7%, respectively. 6 Falcarindiol modulated the nuclear translocation of signal transducer and activator of transcription 1 (Stat1) in a time‐dependent manner. Falcarindiol (50 μM) decreased the tyrosine phosphorylation of janus kinase 1 (JAK1) by 84.8% at 5 min. Falcarindiol also abrogated the tyrosine phoshorylation of JAK2 by 82.3% at 10 min. 7 The present study demonstrates that falcarindiol attenuated the activation of IKK and JAK contributing to the blockade of activation of NF‐κB and Stat1, thereby leading to the suppression of iNOS expression.