Search

Ninjinyoeito (NYT), a traditional Japanese medicine, is effective for improving physical strength and treating fatigue and anorexia. Recently, a clinical report revealed that NYT ameliorates cognitive dysfunction in Alzheimer's disease (AD) patients, although the mechanisms remain unclear. AD is a neurodegenerative disorder accompanied by a progressive deficit in memory. Current therapeutic agents are largely ineffective in treating cognitive dysfunction in AD patients. In this study, we investigated the effects of NYT on spatial memory impairment in a rat model of dementia. Rats were prepared with transient cerebral ischemia and intraventricular injection of β-amyloid1-42 for 7 days (CI + Aβ). NYT was orally administered for 7 days after cerebral ischemia. We evaluated spatial memory using the Morris water maze and investigated the expression of α-amino-3-hydroxy-5-4-isoxazole propionic acid receptor subunits, the phosphorylation level of glutamate receptor A (GluA)1 at serine sites S831 and S845, and the Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the hippocampus and prefrontal cortex of CI + Aβ rats. In the CI + Aβ rats, NYT treatment shortened the extended time to reach the platform. However, NYT did not restore the decrease in the hippocampal GluA1, GluA2, or CaMKII expression but increased prefrontal cortical phosphorylation levels of S845-GluA1 and CaMKII. Therefore, NYT may alleviate spatial memory impairment by promoting glutamatergic transmission involved in the phosphorylation of S845-GluA1 and CaMKII in the prefrontal cortex of CI + Aβ rats. Our results suggest that NYT is a valuable treatment for AD patients. [ABSTRACT FROM AUTHOR]

Aim: Ginseng, a traditional herbal medicine, has been shown to prevent the progression of dementia, but its therapeutic effects vary because ginseng's components must first be activated by intestinal bacteria before being absorbed into the blood. We therefore focused on a fermented ginseng (FG), which contains activated components prepared by Lactobacillus paracasei A221, and compared its effects with those of non‐FG. In this study, we investigated whether FG is effective on spatial memory impairment in rats. Methods: Rats with spatial memory impairment were prepared with transient cerebral ischemia and intraventricular injection of β‐amyloid 1‐42 for 7 days (CI + Aβ). Oral FG or non‐FG was given for 7 days after the cerebral ischemia. Spatial memory was evaluated using the Morris water maze (MWM). We observed neuronal neuclei‐positive cells to assess hippocampal neuron loss, and investigated the protein expression of caspase‐3 and cleaved caspase‐3 for neuronal apoptosis, ionized calcium‐binding adapter molecule 1 (Iba‐1) for microglia, and glial fibrillary acidic protein for astrocytes. Results: FG treatment in the CI + Aβ‐operated rats shortened the extended time to reach the platform in the MWM, whereas non‐FG treatment did not affect the extended time. FG ameliorated loss of hippocampal cornu amonis (CA)1 neurons and the increase in caspase‐3 and Iba‐1 in the CI + Aβ‐operated rats. Conclusion: FG improved spatial memory impairment in CI + Aβ‐operated rats. The effect of FG might be attributed to the amelioration of apoptotic neuronal cell death and the inactivation of microglia. FG is a more useful treatment for patients with cognitive dysfunction than non‐FG. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Japanese Angelica acutiloba root (Angelica root) is included in several Kampo medicines including Yokukansan (YKS). Angelica root and YKS are used for the treatment of a variety of psychological and neurodegenerative disorders. Development of safe and effective therapeutic agents against cerebrovascular disorders will improve the treatment of patients with dementia. Aim of the study The effect of Angelica root and YKS on ischemia-impaired memory has not yet been fully investigated. The present study investigated whether Angelica root is also involved in memory improving and neuroprotective effect of YKS in a model of cerebrovascular ischemia. Materials and methods Male Wistar rats grouped into sham rats received saline, and other three groups subjected to repeated cerebral ischemia induced by 4-vessel occlusion (4-VO), received a 7-day oral administration of either saline, Angelica root or YKS. Memory was evaluated by eight-arm radial maze task. Acetylcholine release (ACh) in the dorsal hippocampus was investigated by microdialysis-HPLC. Apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated fluorescein-deoxyuridine triphosphate (dUTP) nick-end labeling. Results Ischemia induced apoptosis, reduced release of ACh, and impaired the memory (increased error choices and decreased correct choices). Angelica root and YKS improved the memory deficits, upregulated the release of ACh and prevented 4-VO-induced hippocampal apoptosis. Conclusion The dual ACh-increasing and neuroprotective effect of Angelica root could make it a promising therapeutic agent useful for the treatment of symptoms of cerebrovascular dementia. Angelica root could be one of the components contributing to the memory-improving and neuroprotective effects of YKS. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Symptoms of dementia are classified into cognitive dysfunction and behavioral and psychological symptoms of dementia, including sleep disturbance. Yokukansan ( YKS) is effective for sleep disturbance in patients with dementia, but the mechanisms are still unclear. In this study, we evaluated sleep disturbance in rats with cerebral ischemia. We investigated the effect of YKS on sleep disturbance in cerebral ischemia-treated rats. Methods Cerebral ischemia was induced by twice occluding both of the common carotid arteries. Wakefulness, non-rapid eye movement ( NREM) sleep, and rapid eye movement ( REM) sleep were classified using electroencephalography and electromyography. mRNA expression of sleep-wakefulness signals were quantified using reverse transcription-polymerase chain reaction. Results Rats with cerebral ischemia had a higher total wakefulness time and lower total NREM sleep time during the light phase. These changes were ameliorated with 1000 mg/kg YKS for 14 days, but not 3 mg/kg donepezil for 7 days. mRNA expression of the prefrontal cortical prostaglandin ( PG) E2 ( EP4) receptor and of the PGD2 ( DP) receptor was increased by cerebral ischemia. Elevated prefrontal cortical EP4 and DP receptor mRNA expression was reduced by YKS treatment. Conclusion Rats with cerebral ischemia had NREM sleep disturbance. YKS might reduce this sleep disturbance by preventing neuroinflammation, and this was mediated by the EP4 and DP receptors in the prefrontal cortex. [ABSTRACT FROM AUTHOR]