Falcarindiol impairs the expression of inducible nitric oxide synthase by abrogating the activation of IKK and JAK in rat primary astrocytes
2009
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.
British Journal of Pharmacology (2005) 144, 42–51. doi:10.1038/sj.bjp.0706022
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