- 學位論文
大蒜精油及其活性成分之抗憂鬱作用機制研究
Investigation the mechanism of antidepressant-like effects of garlic essential oil and its bioactive compound
摘要
根據世界衛生組織 (WHO) 於 2008 年以失能調整生命年 (DALY) 指標預測憂鬱症至 2030 年成為全球疾病負擔的第二名。研究指出自 1990 至 2010 台灣憂鬱焦慮患者比例倍增。因此，若能從天然食物中找尋具有對抗憂鬱效能或潛力之成分，以此開發機能性食品，特別是針對亞健康族群可做為預防或延緩憂鬱症的發生，並以此降低社會、經濟的損失及醫療成本的支出。近年來，大蒜於學術上的研究廣泛，主要的研究為抗菌、抗發炎、抗氧化、抗血栓、抗癌抗腫瘤、調節血脂及護肝之作用，但對於抗憂鬱相關研究則較為有限。本研究目的為探討大蒜精油 (garlic essential oil, GEO) 及其活性成分二丙烯基二硫化物 (diallyl disulfide, DADS) 對於強迫游泳試驗 (forced swimming test, FST) 和不可預期性的慢性溫和壓力試驗 (unpredictable chronic mild stress, UCMS) 誘導之類憂鬱大鼠是否具抗憂鬱效果。實驗其間給予每公斤體重 25 和 50 毫克之大蒜精油和每公斤體重 10 和 20 毫克之大蒜精油中主要活性成分 DADS，其結果顯示在強迫游試驗中 GEO 夠顯著降低不活動時間及增加游泳的時間，且 GEO 能夠有效改善蔗糖偏好程度下降及增加開放空間 試 驗 中 的 總 移 動 距 離 。 以 高 效 能 液 相 層 析 (high performance liquid chromatography, HPLC) 檢測腦部單胺類物質含量並計算其代謝轉換比率，發現GEO 及其活性成分 DADS 能夠顯著降低因壓力引致代謝速率升高的情形及增加多巴胺和血清素含量。在蛋白質表現方面，大蒜精油能顯著增加海馬迴腦源性神經滋養因子 (brain-derived neurotrophic factor, BDNF) 和 PDS-95 蛋白質表現量及提升海馬迴環化單磷酸腺苷反應元件結合蛋白 (cAMP response element binding protein, CREB) 與蛋白質激酶 B (protein kinase B, AKT) 磷酸化型態之表現。綜合上述結果，GEO 可藉由增加單胺類物質合成及降低代謝轉換比率，透過多巴胺及血清素系統共同之影響來調節神經傳導物質。此外，亦能同時提升額葉皮質及海馬迴中腦源性神經滋養因子相關路徑表現而達到抗憂鬱之功效。
並列摘要
Depression is one of the most prevalent chronic neuropsychiatric disorders that expected to increase over the next 10 years. Due to the limitation of efficacy and undesirable adverse effects of antidepressant, the chronic and recurrent depression is still present at high rates. Accordingly, it is important to develop efficient and safe drugs as alternative therapeutics for mental illness. Forced swimming test (FST) is a very effective and well-established platform to predict the antidepressant efficacy in rodent. Garlic is a dietary supplement derived from the bulb of Allium sativum and widely used as a flavoring agent for food and a medicinal agent for the treatment of a variety of diseases. The antidepressant property of garlic essential oil (GEO) has not been reported scientifically. The present study investigated the possible antidepressant-like effects of repeated (28 days) administration of GEO, which dosage are 25 and 50 mg/kg bw by gavage to rats exposed to a forced swimming test (FST). In addition, GEO has been reported to contain more than 30 organosulfur compounds (OSCs), and DAS, DADS, and DATS have been identified as the three major components. The result showed that GEO decreased the immobility time in the FST without accompanying changes in general activity in the open field test (OFT) during treatment, suggesting an antidepressant-like effect. In addition, unpredictable chronic mild stress (UCMS) employs exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response. Treatment GEO significantly reversed the sucrose preference and restored the higher turnover ratio of serotonin (5-HT) and dopamine (DA) in prefrontal cortex and hippocampus in unpredictable chronic mild stress. Furthermore, GEO not only increased brain-derived neurotrophic factor (BDNF) expression, but also promoted phosphorylation of cAMP response element binding protein (CREB) and protein kinase B (AKT) in prefrontal cortex and hippocampus.