Exploration and identification of kampo medicines as therapeutic agent for Alzheimer's disease targeting tau protein

To find novel dementia-therapeutic Kampo medicines, we examined the effects of orengedokuto (OGT) and sanosyasinto (SST), kampo medicines including Scutellaria root, on memory deficit and brain GSK-3β activity in 6-month-old senescence-accelerated prone mice (SAMP8), an aging animal model. The administration of these Kampo medicines significantly improved object recognition memory deficit of SAMP8. Moreover, OGT and SST administration significantly suppressed CRMP2 phosphorylation by inhibiting age-dependent GSK-3β activation in cortex of SAMP8. On the other hand, tau phosphorylation did not differ between each group, indicating that the phosphorylation of CRMP2 but not tau is involved in early cognitive impairment in SAMP8. These results suggest that OGT and SST could have the potency to be a novel therapeutic agent for dementia, and that CRMP2 may be a new biomarker for dementia.