Inhibitory Actions of Tetrandrine on Tumor Necrosis Factor α-Induced NF-κB Activation in Neovascularization of Cultured Choroidal Explants

Minoru Kikuchi, Shusuke Kamimura, Masaaki Nomura, Tatsuo Takahashi, Nobuyoshi Hagino, Shinjiro Kobayashi
2010 Chinese Medicine  
Tetrandrine (1 μM), a bis-benzylisoquinoline alkaloid isolated from Stephania tetrandra S Moore, significantly decreased tumor necrosis factor alpha (TNFα; 10 ng/ml)-induced increase in the number of micro vessels that budded from cultured rat choroidal explants. Tetrandrine also decreased the TNFα-induced increase in the number of cells composing the microvessels. Ammonium pyrrolidine dithiocarbamate (APDC; 0.1-0.3 μM), an inhibitor of nuclear factor-B (NF-κB), decreased the TNFα-induced
more » ... he TNFα-induced increase in the number of microvessels in a concentration-dependent manner. TNF increased the phosphorylation and degradation of inhibitor of NF-κB (IκBα), as well as increasing the DNA-binding activity of NF-B in choroidal explants. TNF induced an increase of vascular endothelial growth factor (VEGF)-A mRNA, but not VEGF-C mRNA or VEGF-D mRNA. TNF-induced angiogenic action was inhibited by treatment of VEGF-A antibody in cultured choroidal capillaries. Tetrandrine inhibited the TNFα-induced increases of phosphorylation and degradation of IκBα, and reduced the TNFα-induced increase of DNA-binding activity of NF-κB in choroidal explants. In conclusion, tetrandrine inhibits TNF-induced activation of NF-B in the choroidal capillaries via inhibition of TNFα-induced phosphorylation of IκBα.
doi:10.4236/cm.2010.13015 fatcat:qy4c2eoqardwvi4npxy3h5k7xa