本研究首先針對補骨脂粗抽及其各分層萃取物於離體對乙醯膽鹼酯酶活性抑制作用之評估。結果顯示補骨脂粗抽及其各分層萃取物具抑制乙醯膽鹼酯酶活性之作用。進一步探討補骨脂粗抽物及各分層萃取物對 scopolamine 誘發大鼠於被動學習反應及水迷宮學習操作障礙空間操作能力之改善作用。結果發現補骨脂粗抽物及其各分層萃取物具改善大鼠scopolamine誘發學習記憶障礙之作用，其中以氯仿層及乙酸乙酯層之作用較佳。 接著測定補骨脂粗抽物及各分層之補骨脂素及異補骨脂素之含量，結果顯示氯仿層含有較高之補骨脂素及異補骨脂。因此，本研究繼續探討補骨脂素及異補骨脂素於離體對乙醯膽鹼酯酶活性之抑制作用；結果亦顯示補骨脂素及異補骨脂素可抑制乙醯膽鹼酯酶之活性。而後，更進一步針對補骨脂素及異補骨脂素對 scopolamine 誘發大鼠被動迴避學習操作障礙、水迷宮空間操作暨參考記憶障礙之作用進行評估。結果顯示補骨脂素及異補骨脂素均具改善 scopolamine 誘發學習記憶障礙之作用，其中尤以補骨脂素之效果較佳。 最後探討補骨脂素及異補骨脂素改善 scopolamine 誘發學習操作障礙之作用機轉－包括中樞乙醯膽鹼神經系統與單胺神經系統。結果顯示補骨脂素及異補骨脂素可選擇性降低海馬回乙醯膽鹼酯酶之活性，增加 DA、5-HT 及皮質區 NE、EPI 之濃度。 綜合上述研究結果顯示，補骨脂可改善 scopolamine 誘導學習記憶障礙之作用，而補骨脂素為記憶改善作用上之有效活性成分之一。作用機轉與選擇性抑制海馬回乙醯膽鹼酯酶活性及經由抑制 monoamine oxidase 活性以增加海馬回 DA、5-HT 及皮質區 NE、EPI之濃度有關。; The present study was firstly designed to investigate the inhibitory effects of the crude extract of Psoraleae Fructus and its fractions on the AChE activity in vitro. The results showed that the crude extract and its fractions inhibited AChE activity. Furthermore, I evaluated the performance impairment of both the passive avoidance test and the Morris water maze test induced by scopolamine in rats. I found that the crude extract and its fractions could ameliorate scopolamine-induced amnesia, and the chloroform and ethylacetate- fractions were better than other fractions. Next, I analyzed the amounts of psoralen and isopsoralen in the crude extract and its fractions by HPLC. The result showed the amounts of psoralen and isopsoralen in the chloroform- fraction were more than those of other fractions. Furtherover, I evaluated the AChE inhibitory activity of psoralen and isopsoralen in vitro and investigated the ameliorating effects of psoralen and isopsoralen on scopolamine-induced performance impairment in rats. The results showed psoralen and isopsoralen could ameliorate scopolamine-induced amnesia in rats. Psoralen was better than isopsoralen. Finally, I evaluated the role of central cholinergic and monoaminergic neuronal system in the ameliorating effects of psoralen and isopsoralen on scopolamine-induced performance impairment. The results showed only psoralen inhibited hippocampal AChE acvitity in rats. I also found that psoralen and isopsoralen increased hippocampal dopamine and serotonin levels, and cortical norepinephrine and epinephrine levels in rats. According to the above results, psoralen and isopsoralen are two active components of Psoraleae Fructus on the reversal from scopolamine-induced performance impairment. It suggests that the ameliorateing effects of psoralen is related to activating the central cholinergic neuronal system via inhibiting AChE activity, and monoaminergic neuronal system via increasing hippocampal DA and 5-HT levels, and cortical NE and EPI levels.
