Effect of hachimijiogan on memory impairment induced by beta‐amyloid combined with cerebral ischemia in rats

Abstract

Aim Alzheimer's disease (AD) is a chronic neurodegenerative condition most often found in older people. Cerebrovascular disease is commonly found in patients with AD. Hachimijiogan (HJG) is a herbal medicine commonly used to treat age‐related disease. The aim of this study was therefore to investigate whether HJG could improve memory impairment in rats treated with amyloid‐β protein (Aβ) and cerebral ischemia (Aβ + CI). Methods Rats were prepared by a combination of intracerebroventricular Aβ injection and transient cerebral ischemia. Spatial memory was evaluated on water maze and eight‐arm radial maze tasks. HJG (1000 mg/kg/day) or donepezil (DPZ; 10 mg/kg/day) was given orally once per day for 7 days before behavioral task assessment. Results HJG reduced the increased time to reach the platform position in Aβ + CI rats in the water maze task as well as DPZ did. Additionally, HJG reduced the increase in errors in Aβ + CI rats in the eight‐arm radial maze task as well as DPZ did. Conclusion HJG ameliorated memory impairment in Aβ + CI rats, indicating that it may be useful for treating AD.

The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation of CREB

“…Furthermore, it has been reported that HJG treatment improved cognitive dysfunction in patients with dementia ( Iwasaki et al, 2004 ). Additionally, several studies, including one of our own, have reported that HJG improves cognitive dysfunction in model animals ( Hirokawa et al, 1994 , 1996 ; Moriyama et al, 2017 ). However, further research is needed to confirm the effects of HJG on cognitive dysfunction.…”

“…Previously, HJG has been used to treat the symptoms of dysuria and benign prostatic hyperplasia in elderly patients. However, in recent years it has been reported that HJG also improves cognitive function ( Hirokawa et al, 1994 , 1996 ; Iwasaki et al, 2004 ; Moriyama et al, 2017 ). Therefore, we believed it was important to clarify the mechanisms by which HJG improved cognitive function, as this could enable an extension of the therapeutic uses of HJG.…”

“…Aggregated Aβ was prepared as previously described ( Moriyama et al, 2017 ). Aβ42 peptides were purchased from AnaSpec Inc. (Fremont, CA, United States), dissolved in HEPES-buffered solution to a final concentration of 10 μM, and incubated at 37°C for 7 days.…”

“…Cerebral ischemia + Aβ rats were prepared by combining an intracerebroventricular Aβ injection with transient CI as previously described ( Moriyama et al, 2017 ). Rats were anesthetized with sodium pentobarbital.…”

The efficacy and safety of hachimijiogan for mild Alzheimer disease in an exploratory, open standard treatment controlled, randomized allocation, multicenter trial

“…[ 7 ] We recently showed that memory impairment in CI + Aβ rats was ameliorated by HJG administration after ischemia treatment. [ 8 ] Further, we have shown that HJG in vitro exerts a neurotrophic effect via cAMP response element binding protein (CREB) activation, and that HJG ameliorates cognitive dysfunction in dementia model rats via CREB activation. [ 9 ]…”