Effect of Tiantai No.1 on beta-amyloid-induced neurotoxicity and NF-kappa B and cAMP responsive element-binding protein.
OBJECTIVE
To investigate the effect and molecular mechanism of Tiantai No.1, a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by beta-amyloid peptides (Abeta) in vitro and its effects on nuclear factor-kappa B (NF-kappa B) and cAMP responsive element-binding protein (CREB) pathways using the gene transfection technique.


METHODS
B104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100, 150, or 200 micro g/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptide1-40 (A beta 1-40, 10 micro mol/L) for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 (A beta 25-35) for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 micro g/mL and 150 micro g/mL for 5 days or co-treated with Tiantai No.1 and A beta 1-40 (5 micro mo/L) for 3 days after electroporation for the evaluation of NF-kappa B and CREB expression.


RESULTS
Pre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta (P<0.05, P<0.01). With a dose-dependent relationship, the same treatments increased the expression of NF-kappa B or CREB in B104 neuronal cells (P<0.05, P<0.01). Meanwhile, Tiantai No.1 reduced A beta -40 induced inhibition on NF-kappa B expression (P<0.01).


CONCLUSIONS
Tiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-kappa B and cAMP cellular signal pathways.
WU
Zheng-zhi
ZZ
Shenzhen Institute of Integrated Traditional and Western Medicine (Shenzhen), 518035, China. zhengzhw@yahoo.com.cn
Huang
Andrew C J
AC
de Vellis
Jean
J
LI
Ying-hong
YH
D016229:Amyloid beta-Peptides; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018274:Electroporation; D008156:Luciferases; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000032:analysis*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D014162:Transfection
D016229:Amyloid beta-Peptides; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D008156:Luciferases