天麻水萃物及天麻苷對於不可預期慢性輕度壓力憂鬱症動物模式中單胺類神經傳導物質之調控作用及機轉

The effects and mechanisms of water extract of Gastrodia elata Blume and gastrodin on monoamine neurotransmitters regulation in unpredictable chronic mild stress-induced depressive-like animal model

林毓恩(Yu-En Lin)

指導教授 ： 沈立言

國立臺灣大學/生物資源暨農學院/食品科技研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.02588

摘要

憂鬱症是現代社會常見的精神疾病，除了會造成病患失能（disability）與死亡之外，亦會對病患的家庭及社會帶來負擔。世界衛生組織（World Health Organization, WHO）預測憂鬱症將於2030年攀升至全球十大負擔性疾病首位，但現行臨床用藥具有許多副作用，使得病患的順應度降低，因此開發具有預防或輔助治療憂鬱症的療法是十分迫切的。天麻（Gastrodia elata Bl.）係蘭科（Orchidaceae family）植物，其塊莖為傳統中醫常用的食療素材，常作安神寧腦之用。本研究目的為探討天麻及其活性成分天麻苷（gastrodin, GAS），對於不可預期慢性輕度壓力（unpredictable chronic mild stress, UCMS）誘導之憂鬱症大鼠，是否具抗憂鬱效果。進一步以PC12（pheochromocytoma）細胞株研究其於神經傳導物質之可能機轉。實驗期給予四週慢性壓力以誘發大鼠之憂鬱行為，並同時介入每公斤體重0.5克之天麻水萃物（water extract of Gastrodia elata Bl., WGE），結果顯示WGE能夠有效改善因壓力所導致之體重、攝食量、飲水量及蔗糖偏好程度下降，以及開放空間試驗中自主行為（總移動距離、穿越次數、探索站立次數、理毛次數）減低的情形，同時降低因壓力升高之血清皮質固醇濃度及脂質過氧化程度。以高效能液相層析（high performance liquid chromatography, HPLC）檢測腦部單胺類物質含量，並計算其代謝速率，發現WGE能夠顯著降低因壓力引致代謝速率升高的情形。細胞模式以0.5 mg/mL WGE及52、104、208 μM GAS針對單胺氧化酶（monoamine oxidase A, MAOA）反應，顯示104、208 μM GAS具直接抑制效果；將WGE及各濃度GAS介入PC12細胞48小時，各處理皆能顯著降低MAOA的活性及蛋白表現量，同時增加酪胺酸羥化酶（tyrosine hydroxylase, TH）蛋白表現量。而0.5 mg/mL之WGE處理PC12為期30分鐘，亦具有顯著活化釋放相關訊息傳遞路徑，以增加單胺類物質釋放之功效。綜合上述結果，WGE及GAS可藉由降低MAOA的活性及蛋白表現量以降低單胺類物質分解、增加TH的蛋白質表現量以增加單胺類物質合成、釋放等作用維持腦部單胺類物質濃度，同時調控皮質固醇濃度以達到抗憂鬱之功效。
關鍵詞：憂鬱症、不可預期慢性輕度壓力、天麻水萃物、天麻苷、單胺類物質

關鍵字

憂鬱症 ； 不可預期慢性輕度壓力 ； 天麻水萃物 ； 天麻苷 ； 單胺類物質

並列摘要

Depression is a multiple causal disease, predicted to be the first contribution of global burden disease in 2030 according to WHO. Due to the side effects of conventional therapies, patient acceptance of medications is low. Therefore it is urgent to look for alternative approaches. Gastrodia elata Blume is a famous Chinese herbal medicine traditionally used to treat neurological disorders. In the present study, we used unpredictable chronic mild stress (UCMS) for a period of 4 weeks to induce depression-like behaviors in rats, and to investigate the impacts of water extract of Gastrodia elata Blume (WGE) and its major compound, gastrodin (GAS) on the dynamic of neurotransmitters. It was observed that WGE treatment (0.5g/kg) significantly reversed the loss of body weight, the decrease of daily intake, sucrose preference and other abnormal behaviors induced by UCMS paradigm. WGE significantly restored the higher turnover rate of serotonin (5-HT) and dopamine (DA) in frontal cortex, hippocampus, striatum, and amygdala. Also, treatment with WGE significantly ameliorated the higher corticosterone and thiobarbituric acid reactive substances (TBARS) levels in serum. Additionally, the in vitro study showed that GAS (104 and 208 μM) directly introduced to pheochromocytoma (PC12) cell lysate possessed inhibitory effects on monoamine oxidase A (MAOA). Cultured with WGE (0.5 mg/ml) and GAS (52, 104 and 208 μM) for 48 hours significantly inhibited MAOA activity, protein expression and up-regulated tyrosine hydroxylase protein expression. Furthermore, cultured with WGE for 30 minutes significantly increased the DA release and activated exocytosis-related signaling transduction. In conclusion, we found that WGE and GAS exhibited monoamine-regulatory effects on depression prevention.
Keywords: depressive disorder, unpredictable chronic mild stress, Gastrodia elata Bl., gastrodin, monoamine neurotransmitters

並列關鍵字

depressive disorder ； unpredictable chronic mild stress ； Gastrodia elata Bl. ； gastrodin ； monoamine neurotransmitters

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