Neuroprotection and spatial memory enhancement of four herbal mixture extract in HT22 hippocampal cells and a mouse model of focal cerebral ischemia

摘要: Four traditional Korean medicinal herbs which act in retarding the aging process, Polygonum multiflorum Thunb., Rehmannia glutinosa (Gaertn) Libosch., Polygala tenuifolia Willd., and Acorus gramineus Soland., were prepared by systematic investigation of Dongeuibogam (Treasured Mirror Eastern Medicine), published early 17th century Korea. This study was performed to evaluate beneficial effects four herbal mixture extract (PMC-12) on hippocampal neuron spatial memory. High performance liquid chromatography (HPLC) analysis for standardization PMC-12. Cell viability, lactate dehydrogenase, flow cytometry, reactive oxygen species (ROS), Western blot assays HT22 cells immunohistochemistry behavioral tests a mouse model focal cerebral ischemia order observe alterations cell survival subsequent memory function. In HPLC analysis, PMC-12 standardized contain 3.09 % 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, 0.35 % 3′,6-disinapoyl sucrose, 0.79 % catalpol. cells, pretreatment with resulted significantly reduced glutamate-induced apoptotic death. Pretreatment also suppression ROS accumulation connection cellular Ca2+ level after exposure glutamate. Expression levels phosphorylated p38 mitogen-activated protein kinases (MAPK) dephosphorylated phosphatidylinositol-3 kinase (PI3K) glutamate recovered either or anti-oxidant N-acetyl-L-cysteine (NAC). mature brain-derived neurotrophic factor (BDNF) cAMP response element binding (CREB) enhanced treatment NAC. Combination PMC-12, NAC, intracellular inhibitor BAPTA showed similar expression levels. ischemia, we observed higher BDNF phosphorylation CREB hippocampus further confirmed improved Our results suggest that mainly exerted protective neurons through Ca2+-related regulation signaling pathways MAPK PI3K associated subsequently