New Four-herb Formula Ameliorates Memory Impairments via Neuroprotective Effects on Hippocampal Cells

Abstract

The current study was conducted to evaluate beneficial effects of a new formula (CWC-9) using four traditional Oriental medicinal herbs, Cynanchum wilfordii, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, on hippocampal cells and memory function. To examine the neuroprotective effects of a new four-herb extract, cell viability, cytotoxicity, and reactive oxygen species (ROS) assays were performed in HT22 cells and behavioral tests (Morris water maze and passive avoidance retention), Western blot, and immunohistochemistry were performed in a mouse model of focal cerebral ischemia. In HT22 hippocampal cells, pretreatment with CWC-9 resulted in significantly reduced glutamate-induced cell death with suppression of ROS accumulation caused by glutamate. In a mouse model of focal cerebral ischemia, we observed significant improvement of spatial and short-term memory function by treatment with CWC-9. Phosphorylated p38 mitogen-activated protein kinases (MAPK) in hippocampus of ischemic mice were decreased by treatment with CWC-9, but phosphorylated phosphatidylinositol-3 kinase (PI3K) and cAMP response element binding protein (CREB) were significantly enhanced. By immunohistochemical analysis, we confirmed higher expression of phosphorylation of CREB in the hippocampal neurons of CWC-9 treated mice. These results suggest that new multi-herb formula CWC-9 mainly exerted beneficial effects on cognitive function through regulation of neuroprotective signaling pathways associated with CREB.

Prospective stem cell lines as in vitro neurodegenerative disease models for natural product research

“…These cells have been used to evaluate the neuroprotection activity of herbal medicines intended for the treatment of ND. A study showed that four traditional Oriental medicinal herbs protect the rat hippocampal cells from glutamateinduced toxicity by reducing the ROS production and increasing cell viability [61]. Although these cell lines provide a promising approach to evaluate the neuroprotection and neuroregeneration potential of herbal medicines, its action is limited to the animal AD, and it cannot induce the full range of deficits seen in human with AD due to lack of receptor for human Aβ peptides [59].…”