梔子及其活性成分去羥梔子苷、梔子苷元對小鼠憂鬱模式抗憂鬱作用機轉之研究;Action mechanism of the anti-depressive effect of Gardeniae Frutus and its active constituents - geniposide and genipin in depressive models of mice

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题名:	梔子及其活性成分去羥梔子苷、梔子苷元對小鼠憂鬱模式抗憂鬱作用機轉之研究;Action mechanism of the anti-depressive effect of Gardeniae Frutus and its active constituents - geniposide and genipin in depressive models of mice
作者:	黃淑雯;Shu-Wen Huang
贡献者:	中國醫藥大學：中國藥學研究所碩士班
关键词:	梔子;抗憂鬱;強迫游泳試驗;尾部懸吊試驗;去羥梔子甘;梔子苷;元;anti-depressive;Gardeniae Frutus;forced swimming test;Tail suspension test;geniposide;genipin
日期:	2007-06-03
上传时间:	2009-08-11 10:25:23 (UTC+8)
摘要:	本研究首先探討山梔子、水梔子乙醇粗抽物及其活性成分去羥梔子苷(GPO)、梔子苷元(GPI)於強迫游泳試驗法及尾部懸吊試驗法之抗憂鬱作用，其次，併用臨床常用抗憂鬱藥物fluoxetine (FLU,選擇性血清素再回收抑制劑)、desipramine (DES, 三環抗憂鬱劑,正腎上腺素及血清素再回收抑制劑)、maprotiline (MAP,選擇性正腎上腺素再回收抑制劑) 與clorgyline (CLO,單胺氧化酶A型抑制劑)，評估GPO及GPI抗憂鬱作用之可能機轉。最後測定小鼠海馬迴、紋狀體與大腦皮質等腦組織中神經傳導物質：正腎上腺素(norepinephrine) 、血清素(serotonin)、多巴胺(dopamine)及其代謝物的濃度，探討GPO及GPI抗憂鬱作用機轉與腦內各部位神經傳導物質的關係。結果顯示，山梔子、水梔子乙醇粗抽物 (0.1, 1.0 g/kg, p.o.)及其活性成分GPO (5.0, 10 mg/kg, i.p.)、GPI (5.0, 10 mg/kg, i.p.)均可減少強迫游泳試驗及尾部懸吊試驗的小鼠不動時間，且不影響小鼠運動量。在強迫游泳試驗中，GPO(10 mg/kg, i.p.)、GPI(10 mg/kg, i.p.)有增強DES(5.0 mg/kg)及FLU(5.0 mg/kg)的抗憂鬱作用，但不影響CLO與MAP的抗憂鬱作用。在小鼠腦內單胺濃度實驗中，GPO(10 mg/kg) 能提高小鼠紋狀體及海馬迴血清素含量及紋狀體中血清素代謝物5-HIAA的含量。而GPI(10 mg/kg)，則能增加小鼠大腦皮質、紋狀體及海馬迴之血清素及其代謝物5-HIAA的含量，並增加海馬迴DOPAC的含量。綜合以上結果顯示，梔子乙醇粗抽物及其活性成分去羥梔子苷和梔子苷元在強迫游泳試驗及尾部懸吊試驗中，均有明顯的抗憂鬱作用。去羥梔子苷及梔子苷元之抗憂鬱作用機轉可能與提升腦內紋狀體、海馬迴及大腦皮質的血清素含量有關。 The aim of present study was to evaluate the anti-depressive activity of ethanol extracts of Gardenia jasminoides Ellis. (GJ EtOH) and Gardenia jasminoides Ellis. var. grandiflora Nakai.(GJG EtOH) (Family: Rubiaceae), geniposide (GPO), and genipin (GPI) by mouse forced swimming test (FST) and tail suspension test (TST). In addition, the probable mechanisms of action of anti-depressive effect of GPO and GPI were investigated by combining the antidepressant drugs, fluoxetine (FLU, a selective serotonin reuptake inhibitor), desipramine (DES, a tricyclic antidepressant, monoamine reuptake inhibitor), maprotiline (MAP, selective noradrenaline reuptake inhibitor) and clorgyline (CLO, a selective MAO- A inhibitor) and measuring the levels of norepinephrine, serotonin, dopamine and its metabolites in mice hippocampus, striatum and cortex. GJEtOH (0.1, 1.0 g/kg, p.o.), GJG EtOH (0.1, 1.0 g/kg, p.o.), GPO (5.0, 10 mg/kg, i.p.) and GPI (5.0, 10 mg/kg, i.p.) significantly reduced the immobility time of mice in both FST and TST, and did not significantly affect the locomotor activity of mice. GPO (10 mg/kg, i.p.) and GPI (10 mg/kg, i.p.) augmented the anti-depressive effect of DES (5 mg/kg, i.p.) and FLU (5 mg/kg i.p.) in the FST, and did not affect the anti-depressive effect of CLO and MAP. GPO (10 mg/kg, i.p.) increased the levels of serotonin and 5-hydroxyindole-3-acetic acid (5-HIAA) in striatum and the level of serotonin in hippocampus. GPI (10 mg/kg, i.p.) increased the levels of serotonin and 5-HIAA in striatum, hippocampus and cortex and the level of DOPAC in the hippocampus. Our findings support the view that GJEtOH, GJGEtOH, GPO and GPI produced antidepressant-like effect in both FST and TST. The mechanisms of action of anti-depressive effect of GPO and GPI seem to be mediated by increasing the serotonin level in hippocampus, cortex and striatum of mice.
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