The mechanisms of the memory-improving and neuroprotecting effects of Fraxini Cortex and its coumarins

• Main Authors: Ping-Ying Hsieh, 謝坪螢
• Other Authors: 吳啟瑞
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/64983994269283827738

碩士 === 中國醫藥大學 === 中國藥學研究所碩士班 === 95 === In this study, the antioxidant properties of Fraxini Cortex and its simple coumarins were evaluated by scavenging superoxide anion radical and hydrogen peroxide assays. The effects of esculetin and fraxetin on the inhibition of monoamine oxidase and acetylcholinesterase, and 6-OHDA-induced oxidative damage in SH-SY5Y cells were examined in vitro. In addition, I also explored the mechanism of the ameliorating effects of esculetin and fraxetin on scopolamine-induced performance impairment of Morris water maze in rats. First, the results showed that chloroform fraction of Fraxini Cortex, enriched esculetin and fraxetin contents, possessed free radicals scavenging activity. Esculetin possessed the better MAO-inhibiting effect than fraxetin. Moreover, esculetin also had the better protecting effects than fraxetin and pargyline on 6-OHDA-induced neuronal damage in SH-SY5Y cells. Esculetin increased cell viability, reversed the alteration of DCFH-DA and JC-1 fluorescence intensity in 6-OHDA-treated SH-SY5Y cells. Secondly, esculetin and fraxetin inhibited the acetylcholinesterase activity and ameliorated scopolamine-induced amnesia in rats. Esculetin selectively inhibited the activity of acetylcholinesterase and increased the concentration of NE, DA in hippocampus. Fraxetin inhibited the activity of acetylcholinesterase and monoamine oxidase, and increased the concentration of DA levels in striatum. In conclusion, Fraxini Cortex and its active components - esculetin and fraxetin possessed antioxidant and acetylcholinesterase inhibiting activities. The ameliorating effect of esculetin on the scopolamine-induced performance impairment was better than that of fraxetin in rats. The ameliorating mechanisms of esculetin were related to the decrease in the acetylcholinesterase activity and the increase in the NE and DA levels in hippocampus. Only esculetin protected the 6-OHDA-induced oxidative damage in SH-SY5Y cells via decreasing intracellular oxidative stress and slowing down the mitochondrial dysfunction. Therefore, Fraxini Cortex and its coumarins are potential for prevention and treatment of neurodegenerative diseases.