Beneficial Effects ofPolygonum multiflorumon Hippocampal Neuronal Cells and Mouse Focal Cerebral Ischemia

Beneficial effects of the water extract of Polygonum multiflorum (WEPM) and their mechanisms were investigated in HT22 hippocampal cells and hippocampus of middle cerebral artery occlusion (MCAO) mice. In HT22 cells against glutamate-induced oxidative stress, pretreatment with WEPM resulted in significantly reduced apoptotic neuronal death. Pretreatment with WEPM resulted in the suppression of ROS accumulation in connection with cellular Ca (2+) level after exposure to glutamate. Treatment with glutamate alone led to suppressed protein level of mature brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (CREB); however, pretreatment with either WEPM or anti-oxidant N-acetyl-ʟ-cysteine (NAC) resulted in the significant enhancement of levels of these proteins. In addition, levels of mature BDNF expression and CREB phosphorylation were increased by combined treatment with WEPM, NAC, and intracellular Ca (2+) inhibitor BAPTA compared to other treatment groups. In MCAO mice, we confirmed the critical role of mature BDNF expression and CREB phosphorylation by WEPM in the neurons of the hippocampus. Our results suggest that WEPM mainly exerted beneficial effects on hippocampal neurons through the suppression of ROS accumulation and up-regulation of mature BDNF expression and CREB phosphorylation.