Ameliorative effects of yokukansan on behavioral deficits following transient forebrain ischemia in gerbils
Yanan Liu, Takehiro Nakamura, Tetsuhiko Toyoshima, Feng Lu, Tohru Yamamoto, Toshifumi Itano
Department of Molecular Neurobiology, Kagawa University Faculty of Medicine

Objective: The traditional herbal medicine yokukansan (YKS) has been used for the treatment of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease and other forms of senile dementia. Although accumulated evidence indicates the beneficial effect of YKS on the BPSD, few information is available on the effect of YKS on memory impairment induced by brain ischemia. The present study we investigated whether YKS has protective effect on ischemic dementia induced by cerebral ischemia reperfusion injury in gerbils.
Methods: Male Mongolian gerbils were treated with YKS by oral for a period of 30 days once per day until the day before induction of ischemia, which was induced by occluding the bilateral common carotid artery for 5min. Distilled water was administered to the control groups at the same time points. The effects of YKS were examined by measuring neuronal damage with a dose-dependent manner (50 mg/kg; 100 mg/kg; 300 mg/kg) and behavioral deficits (locomotor activity, 8-arm radial maze task). The anti-inflammatory and anti-oxidant properties of YKS were also detected for mechanism investigation.
Results: Administration of YKS with the dosage at 300 mg/kg significantly reduced hippocampal neuronal death after brain ischemia, neither 50 mg/kg nor 100 mg/kg YKS provided neuroprotection. YKS at 300 mg/kg significantly decreased the number of Iba1 (microglia marker) positive cells, the level of 8-OHdG (DNA oxidation marker) and also reduced the locomotor activity 72h after transient forebrain ischemia and the number of errors in 8-arm radial maze task.
Conclusions: The present study suggests that YKS treatment ameliorates behavioral dysfunction after transient forebrain ischemia by suppressing neuronal damage. This beneficial effect of YKS may have potential for ischemic stroke.