Neuroprotective effects of Kangen-karyu on spatial memory impairment in an 8-arm radial maze and neuronal death in the hippocampal CA1 region induced by repeated cerebral ischemia in rats.

In the present study, we investigated the neuroprotective effects of Kangen-karyu (KGK) in a repeated cerebral ischemia model (2 x 10 min, 1-h interval). A 21-day pre- and post-ischemic treatment with KGK (10 - 300 mg/kg) and aspirin (5 mg/kg) improved the spatial memory impairment and neuronal death in the hippocampal CA1 region induced by repeated cerebral ischemia. However, a 7-day post-ischemic treatment with KGK did not attenuate the spatial memory impairment and neuronal death in this model. To determine the mechanism of action of KGK, we investigated the effects of a 14-day pre-ischemic treatment with KGK on cerebral blood flow in the hippocampal area of the repeated cerebral ischemia model using laser Doppler flowmetry. The 14-day pre-ischemic treatment with KGK increased the cerebral blood flow during reperfusion. These results suggest that a 21-day pre- and post-ischemic treatment with KGK can protect against brain damage caused by cerebral ischemia by increasing the cerebral blood flow in the hippocampal area.

Yokukansan inhibits social isolation-induced aggression and methamphetamine-induced hyperlocomotion in rodents.

Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as on that of their caregivers. However, effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD, such as aggression, agitation, irritability, and hallucinations, in a randomized, single-blind, placebo-controlled study. However, the psychopharmacologic effects of YKS remain unexplored. In the present study, we investigated the effects of YKS on social isolation-induced aggressive behavior and methamphetamine- or MK-801-induced hyperlocomotion in rodents. Social isolation markedly induced aggressive behavior in male Wistar rats. Quetiapine at a dose of 10 mg/kg (per os (p.o.)) significantly inhibited this social isolation-induced aggressive behavior. YKS (100, 300 mg/kg, p.o.) also significantly inhibited the aggressive behavior. Moreover, risperidone (0.1 mg/kg, p.o.) significantly inhibited methamphetamine- or MK-801-induced hyperlocomotion in mice. YKS (300 mg/kg, p.o.) inhibited methamphetamine-induced hyperlocomotion, while YKS at the same dose had no effect on MK-801-induced hyperlocomotion. These findings suggest that YKS may be useful for the treatment of aggression and agitation, and that the psychopharmacologic effects of YKS might be mediated, in part, by inhibiting the activity of the dopaminergic system.

Kamikihi-to, a Kampo medicine, ameliorates impairment of spatial memory in rats.

The present study investigated the effects of Kamikihi-to (KKT), a Kampo medicine, on impairment of spatial memory in rats using an eight-arm radial maze task. Scopolamine (0.5 mg/kg, i.p.), a non-selective muscarinic receptor antagonist, and Delta(9)-tetrahydrocannabinol (THC; 6 mg/kg, i.p.), a principal psychoactive component of marihuana, each markedly impaired the spatial memory. KKT (1 and 3 mg/kg, p.o.) significantly improved the scopolamine-induced impairment of spatial memory. KKT (30 mg/kg, p.o.) also improved significantly the THC-induced impairment of spatial memory. Moreover, KKT (3 and 30 mg/kg, p.o.) enhanced tremors induced by oxotremorine, a muscarinic M(1) receptor agonist. Taken together these findings suggest that KKT is a useful drug for treating memory deficits.