Tetrandrine inhibits signal-induced NF-κB activation in rat alveolar macrophages

Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from a natural Chinese herbal medicine. While this alkaloid has been shown to exhibit antifibrotic and anti-inflammatory activities, its mechanism of action is unknown. The present study was designed to investigate the inhibitory effect of tetrandrine on NF-κB activation in the alveolar macrophage. Three different provocative stimuli were used to activate NF-κB in these cells. The results indicate that tetrandrine can inhibit the activation of NF-κB and NF-κB-dependent reporter gene expression by LPS, PMA, and silica in a dose-dependent manner. In contrast, at the doses used, tetrandrine did not interfere with Sp-1 DNA binding activity or Sp-1-dependent reporter gene expression in these cells. Western blot analysis suggests that the inhibitory effect of tetrandrine on NF-κB activation can be attributed to its ability to suppress signal-induced degradation 1κBα, a cytoplasmic inhibitor of the NF-κB transcription factor.