富含γ-胺基丁酸之紅麴發酵產物最適生產條件與其抗憂鬱功效評估

Study on the optimal culture condition and evaluation of the antidepressant effect of the GABA-rich Monascus-fermented product

莊佳穎(Chia-Ying Chuang)

指導教授 ： 潘子明

國立臺灣大學/生命科學院/微生物與生化學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.01659

摘要

憂鬱症為主要最常見的神經失調疾病，包括心情及認知能力的改變，及經常有死亡或自殺念頭。現今臨床的治療藥物並不適用於所有患者且會產生副作用，因此尋找具抗憂鬱功效且低副作用的物質為極具價值性的研究方向。γ-胺基丁酸 (γ-aminobutyric acid, GABA) 是一重要的神經傳導物質，且具有許多生理活性，如降血壓、利尿及改善焦慮、憂鬱等情緒相關疾病，在此研究中，利用紅麴探討在不同培養基質及培養條件 (培養時間、pH 值、溫度及接種量) 對 GABA 生成的影響；另一方面，利用強迫游泳動物試驗 (forced swimming test, FST) 評估富含 GABA 的紅麴發酵產物其抗憂鬱功效。利用反應曲面法探討 GABA 最適生成條件，當米糠添加比例為 77.3%、培養基起始 pH 值 6.3 及麩胺酸鈉濃度 122.6 mM 時，發酵 7 天後，GABA 從原本 40 mg/L 提升至 350 mg/L，每克 GABA 生產成本為新台幣 8.5 元。另一方面，在強迫游泳短期試驗顯示，GABA為紅麴發酵產物中主要具抗憂鬱功效之物質；而長期試驗中，紅麴發酵產物比同劑量之 GABA 具更好的抗憂鬱潛力，效果類似於 fluoxetine (臨床抗憂鬱藥劑)。於腦組之中，GABA 能提升杏仁核及海馬迴中正腎上腺素、多巴胺與血清素含量；除此之外，紅麴發酵產物更能減緩杏仁核及海馬迴多巴胺的消耗。因此，富含 GABA 之紅麴發酵產物具有低基質成本與抗憂鬱功效等市場潛力。

關鍵字

紅麴 ； γ-胺基丁酸 ； 成本 ； 強迫游泳試驗 ； 抗憂鬱

並列摘要

Depression is a disorder characterized by a broad range of symptoms, including altered mood and cognitive functions, and recurrent thoughts of death or suicide. The pharmacotherapy used in clinic today is not suitable for all patients and causes certain side-effects. Thus, looking for alternative treatments with antidepressant effect and minimal side-effect is important. γ-Aminobutyric acid (GABA) is a key compound of the major neurotransmitters. It also has several physiological functions, not hypotensive and diuretic effects, but related to anxiety, depression and numerous mood disorders. In this study, various cultivation substrates and culture conditions (cultural time, pH value, temperature and inoculum volume) were selected to investigate the effect on GABA production by Monascus sp. Moreover, the forced swimming test (FST) of animal model was used to evaluate the antidepressant effect of GABA-rich Monascus submerged fermented product (MSF). To explore the GABA optimal culture conditions, response surface methodology experiment was used. When 77.3% rice bran was used as a substrate which initial pH value and monosodium glutamate concentration were 6.3 and 122.6 mM respectively, the GABA increased from 40 mg/L to 350 mg/L in day 7. The cost of GABA was NT $8.5 per gram. On the other hand, the FST data shows that GABA may be the major compound in MSF to provide antidepressant-like effect in short-term test. In long-term test, the MSF had more antidepressant potential than GABA to reduce the immobility time, and as well as fluoxetine (a clinical prescription) in FST. In brain tissue, GABA provide a high potential to recovered the concentration of norepinephrine, dopamine and serotonin in hippocampus and amygdala. However, MSF also can reduce the consumption of dopamine in hippocampus and amygdala. Thus, MSF which with high GABA level has more potential in low production cost and antidepressant-like effect.

並列關鍵字

Monascus ； GABA ； cost ； forced swimming test ； antidepressant

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