The Japanese herbal medicine
kamikihito (
KKT) is widely used for
insomnia,
anorexia,
anemia, and depression. Recently, the efficacy of
KKT against
Alzheimer's disease (AD) has been demonstrated in clinical and non-clinical studies. To address the mechanism underlying the effect of
KKT on AD, we examined the effects of
KKT in β-
amyloid (Aβ)25-35-exposed primary cultured neurons. The effects of
KKT on Aβ25-35-induced neurotoxicity were assessed by immunocytochemical assays and Sholl analysis of neurites, and the influence of
KKT on
neurotrophic factor (NF) gene expression was examined using RT-PCR analysis. As a result, Aβ25-35 exposure attenuated the arborization of neurites of single cultured hippocampal neurons, and
KKT treatment for 3 days ameliorated the Aβ25-35-induced impairment of tau-positive axon outgrowth. This ameliorative effect of
KKT was largely abolished by the Trk inhibitor
K252a, and expression of NFs,
nerve growth factor (
Ngf),
brain-derived neurotrophic factor (
Bdnf), neurotrophin-3 (NT-3) was significantly increased by
KKT. These results indicate that
KKT ameliorates axonal
atrophy via NFs signaling, providing a mechanistic basis for treatment of AD with
KKT.