鬱金及薑黃酮對小鼠憂鬱模式抗憂鬱活性作用機轉之研究;Mechanism of action of the anti-depressive effect of Curcuma aromatica Salisb and its active constituent - turmerone in mice depression models

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Title:	鬱金及薑黃酮對小鼠憂鬱模式抗憂鬱活性作用機轉之研究;Mechanism of action of the anti-depressive effect of Curcuma aromatica Salisb and its active constituent - turmerone in mice depression models
Authors:	葉雅玲;Ya-Ling Yeh
Contributors:	中國醫藥大學：中國藥學研究所碩士班
Keywords:	薑黃酮;抗憂鬱;turmerone;antidepression
Date:	2009-06-04
Issue Date:	2009-08-11 10:25:22 (UTC+8)
Abstract:	本研究首先以強迫游泳試驗法及尾部懸吊試驗法探討一次及一週口服給藥下，鬱金乙醇粗抽物及其活性成分薑黃酮(turmerone)之抗憂鬱作用，其次，併用常用抗憂鬱藥物fluoxetine, desipramine, maprotiline與clorgyline，以強迫游泳試驗法評估薑黃酮抗憂鬱作用之可能機轉。並測定單胺氧化酶A活性進一步探討薑黃酮抗憂鬱作用是否與抑制單胺氧化酶A活性有關。再則，測定小鼠大腦皮質、紋狀體、海馬迴及下視丘的神經傳遞物質及其代謝物的濃度，探討薑黃酮的抗憂鬱作用與腦內單胺神經傳導物質濃度的關係。最後測定小鼠血清中腎上腺素濃度變化，以了解鬱金乙醇粗抽物及薑黃酮抗憂鬱作用與腎上腺素之關係。結果顯示，鬱金乙醇粗抽物(0.2, 1.0 g/kg, po)及薑黃酮(2.5, 5.0 mg/kg, po)一次或一週口服給藥下均可有效減少強迫游泳試驗及尾部懸吊試驗的小鼠不動時間，並且發現小鼠連續服用一週鬱金乙醇粗抽物及薑黃酮後，小鼠不動時間減少比一次給藥的效果略佳，在活動量評估方面，小鼠在服用鬱金乙醇粗抽物及薑黃酮後的運動量與誘導組比較並無顯著性差異。在合併藥物方面，小鼠在一次或一週口服給藥下，薑黃酮(2.5, 5.0 mg/kg, po)有縮短fluoxetine及clorgyline的不動時間，薑黃酮可顯著抑制皮質區及海馬迴區單胺氧化酶A的活性。薑黃酮可提升腦內大腦皮質、紋狀體、海馬迴及下視丘的血清素含量，並減少5-HIAA含量。鬱金乙醇粗抽物及薑黃酮可顯著減少小鼠經強迫游泳試驗後升高的血中corticosterone濃度。綜合以上結果顯示，鬱金乙醇粗抽物及薑黃酮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。薑黃酮之抗憂鬱作用機轉可能與抑制單胺氧化酶A活性而增加血清素的濃度有關。鬱金乙醇粗抽物及薑黃酮之抗憂鬱作用亦與減少血清中corticosterone濃度而減少小鼠壓力有關。 The aim of the present study was to evaluate the anti-depressive activity of ethanol extract of Curcuma aromatica Salis (CAEtoH) (Zingiberaceae) and turmerone after acute and one-week administrations by mouse forced swimming test (FST) and tail suspension test (TST).In addition, the probable mechanisms of action of anti-depressive effect of turmerone was 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 activity of monoamine oxidase and corticosterone level in the blood and monoamines level in the cortex, striatum, hippocampus and hypothalamus. CAEtOH (0.2, 1.0 g/kg, p.o.)and turmerone (2.5, 5.0 mg/kg, p.o.) after acute and one-week administrations significantly reduced the immobility time of mice in both FST and TST, and did not significantly affect the locomotor activity of mice.Turmerone (2.5, 5.0 mg/kg, p.o.) shorten the immobility time of FLU (5 mg/kg, p.o.) and CLO (0.5 mg/kg, p.o.) in the FST,and did not affect the immobility time of MAP and DES. Furthermore, turmerone(2.5, 5.0 mg/kg, p.o.) increased the levels of serotonin in cortex, striatum hippocampus and hypothalamus . CAEtOH and turmerone decreased the corticosterone level in the blood . Our findings support the view that CAEtOH and turmerone after acute and one-week administrations produced antidepressant-like effect in both FST and TST. The mechanisms of action of anti-depressive effect of turmerone seem to increase the serotonin level via decreasing the MAO-A activity and the stress of mice.
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