Tokishakuyakusan: Pharmacological evidence for neuroactive and neuroprotective actions

The present article introduces our study related to the neuroactive and neuroprotective effects of Tokishakuyakusan (TSS) on animal model of Alzheimers disease (AD) or cerebrovascular dementia. Single administration of TSS ameliorates the impairment of spatial memory induced by scopolamine in radial maze test and enhances tremors induced by oxotremorine, a muscarinic M1 receptor agonist. We found that Ang-S-1, which is a partial inverse agonist of benzodiazepine, was an active compound of TSS in improving effect on impairment of spatial memory in radial maze test. We also found that single administration of TSS increased both acetylcholine (ACh) release and blood flow in the dorsal hippocampus, and TSS protected against neurotoxicity induced by amyloid β protein (Aβ). In animal model of AD or cerebrovascular dementia, we found that TSS prevented the impairment of spatial memory, neuronal death and TUNEL positive cells induced by repeated ischemia, and TSS prevented the impairment of spatial memory and decrease of ACh release induced by ovariectomized combined with Aβ. The present findings show that TSS prevents the memory deficits through not only enhancing ACh release but also protecting neuronal damage. Thus, TSS exhibits the neuroactive and neuroprotective effects in animal model of AD or cerebrovascular dementia, and therefore may be useful in the treatment of these dementia.