北冬蟲夏草水萃物可能經由ROCK2/Akt路徑調節在不可預期慢性壓力動物模式中抗憂鬱之功效

Abstract

根據世界衛生組織於2012年指出，全球約三億人口罹患憂鬱症的盛行率會影響了整個社會的經濟結構。而治療過程中服用藥物引起的副作用及不適感會導致患者服藥順從性不佳，使得憂鬱症的治療更加困難，因此利用食補觀念加強疾病預防是當務之急。冬蟲夏草是中國歷史中傳統的名貴中藥材，但由於採集不易等因素而產量逐年下降。北冬蟲夏草（Cordyceps militaris）則被認為是冬蟲夏草良好的取代物，研究發現蟲草素可延長小鼠在水中泳動時間、延緩疲勞。本研究旨在利用類憂鬱症動物模式中，探討北冬蟲夏草水萃物是否可藉由調控發炎激素之濃度，影響Rho-associated kinase protein（ROCK2）及Akt蛋白質表現量，預防神經細胞凋亡並維持單胺類神經傳導物質濃度而達到抗憂鬱之功效。動物實驗利用不可預期慢性壓力（Unpredictable chronic mild stress）持續五週來誘導動物產生類憂鬱傾向，並同時管餵北冬蟲夏草水萃物125 mg/kg bw、250 mg/kg bw、500 mg/kg bw，後續進行蔗糖偏好試驗（Sucrose preference test, SFT）及開場試驗（Open field test, OFT）評估北冬蟲夏草水萃物抗憂鬱功效。研究結果發現，北冬蟲夏草水萃物125 mg/kg bw、250 mg/kg bw可有效減少腦部皮質區Rho-associated protein kinase（ROCK）蛋白質表現量進而調節Akt蛋白質濃度；減少血清細胞激素濃度，並顯著提升腦部皮質區血清素及多巴胺轉換率，也顯著提升動物糖水偏好程度；在開放空間試驗中提升動物總移動距離及各象限跨越次數。綜合上述結果證實北冬蟲夏草水萃物可經由調控發炎反應及ROCK2/Akt蛋白質路徑達到維持單胺類神經傳導物濃度，預防動物在壓力模式下產生憂鬱傾向。

According to world health organization, depression may be the first contribution of global burden disease in 2030. Due to the side effect in treatment and the low reception of drug, the new strategy of preventing depression is required. Cordyceps militaris has been known as a precious Chinese herb in Asia. Researchers had found amounts of neuroprotection effects in recent years such as it can significantly decrease the immobility time in forced swimming test in mice model. Modern scientists have confirmed that the mainly active compound in Cordyceps militaris including cordycepin, poly-saccharides, nucleoside and sterols. The aim of this study is to evaluate the anti-depression effect of Cordyceps militaris precisely. In unpredictable chronic mild stress animal model, Cordyceps militaris maintained the amount of water intake and food intake to prevent weight loss in stress condition. It was observed that Cordyceps militaris (125 mg/kg bw、250 mg/kg bw、500 mg/kg bw) may significantly increase the crossing number and total traveled distance in open field test. Besides, it also increased the sucrose preference. Low dosage of Cordyceps militaris (125 mg/kg bw) significantly decreased the IL-1β in serum. In brain cortex, low dosage of Cordyceps militaris (125 mg/kg bw) might altered the serotonin turnoverate and dopamine turnoverate. In western blotting, the data showed that Cordyceps militaris (125 mg/kg bw、250 mg/kg bw、500 mg/kg bw) may decreased the ROCK2 protein expression and up-regulated the Akt protein expression in cortex. In conclusion, we found that Cordyceps militaris might regulate the IL-1β in serum and further regulated the ROCK2/Akt pathway in anti-depression effect.