Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic A1-42 C. elegans. In worms, DXN significantly increased A monomers and decreased the toxic A oligomers, thus reducing A toxicity. DXN significantly suppressed the expression of
hsp-16.2 induced by juglone, and up-regulated
sod-3 expression. These results indicated that DXN increased stress resistance and protected C. elegans against oxidative stress. Furthermore, DXN could significantly promote DAF-16 nuclear translocation, but it did not activate SKN-1. The inhibitory effect of DXN on the A toxicity was significantly reverted by
daf-16 RNAi, rather than
skn-1 RNAi or
hsf-1 RNAi. These results indicated that DAF-16 is at least partially required for the anti-AD effect of DXN. In conclusion, DXN improved A-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic worms. Together with our data obtained by Morris water maze test, the results showed that DXN markedly ameliorated cognitive performance impairment induced by scopolamine in mice. All the results support that DXN is a potential drug candidate to treat Alzheimer's diseases.