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標題: | 茯苓水萃物經由調控 p38 MAPK 路徑於不可預期慢性輕度壓力誘導模式中減緩動物類憂鬱傾向之功效 Water extract of Poria cocos with anti-depressive effects via modulation of p38 MAPK pathway in unpredictable chronic mild stress-induced depressive-like animal model |
作者: | Nai-Yuan Hsu 許乃元 |
指導教授: | 沈立言(Lee-Yan Sheen) |
關鍵字: | 茯苓,強迫游泳試驗,不可預期慢性輕度壓力,蔗糖偏好試驗,開放空間試驗,有絲分裂活化蛋白質激?, Poria cocos Wolf,forced swim test,unpredictable chronic mild stress,sucrose preference test,open field test,mitogen-activated protein kinase, |
出版年 : | 2017 |
學位: | 碩士 |
摘要: | 憂鬱症是現代社會常見的精神疾病,除了帶來病患失能或是死亡的風險,對於病患家人以及社會更是沈重的負擔,世界衛生組織預測,在 2030 年憂鬱症將會攀升至全球負擔性疾病首位。臨床證據顯示當體內處於發炎狀態時,憂鬱症的發生率顯著較高,而憂鬱症病患血液中促發炎細胞激素也有提升的現象。目前憂鬱症最主要透過抗憂鬱藥物的治療為主,許多研究都證實抗憂鬱藥物具有良好的功效,但在臨床應用上卻因其副作用而導致病患的順應性低下,因此,發展憂鬱症的預防及替代療法當前迫切需要的課題。茯苓(Poria cocos Schw. Wolf) ,是一種多孔菌科乾燥真菌的菌核。最初記載於本草經,味甘、性平,具有養心安神、益脾和胃、利水滲濕之功效,已有千年的食用歷史。現代醫學研究顯示,茯苓具有抗腫瘤、抗發炎及抗氧化等的功效。因此,本實驗欲利用強迫游泳試驗及不可預期慢性輕度壓力等急、慢性動物模式誘導大鼠產生類憂鬱傾向,並觀察介入不同劑量之茯苓水萃物是否具有抗憂鬱的效果。結果顯示,茯苓水萃物能顯著減少大鼠的不泳動時間,且給予茯苓水萃物 300 mg/kg bw 之組別能藉由減少血清素代謝速率改善動物類憂鬱症狀,以及因壓力而造成蔗糖偏好下降以及探索能力下降的現象,與負控制組相比,能顯著提升蔗糖偏好程度約 26% 及探索能力約 55%。此外,壓力會造成 p38 MAPK(p38 Mitogen-activated protein kinases)蛋白磷酸化比例上升,會進一步啟動下游轉錄因子 NF-κB(nuclear factor kappaB)之訊息傳遞而產生大量促發炎細胞激素腫瘤壞死因子-α(tumor neucrosis factor alpha, TNF-α)。由以上結果推測,茯苓水萃物於強迫游泳試驗中可以藉由降低血清素代謝速率約 44% 達到抗憂鬱的效果,並於不可預期慢性輕度壓力試驗中藉由減少 p38 MAPK 相關蛋白路徑表現量約 34-42%,降低大鼠發炎反應,達到抗憂鬱的功效,由此可見茯苓於預防甚至輔助治療憂鬱症,甚至在未來開發成為菇類抗憂鬱的保健產品皆具有相當高的潛力。 Depression is a chronic illness that significantly affects a person’s moods, behaviour and general health. Predicted to be the first contribution of global burden disease in 2030 according to WHO. Inflammation is a protective response of the human body to various harmful stimuli including physical trauma, noxious chemicals, and microbiologic agents. However, chronic inflammation can lead to serious tissue damage and inflammation-associated diseases, like depression. At present, there are several classes of classical antidepressants in clinical practice. However, most of these drugs are undesirable, due to their side effects and efficacy for only a certain proportion of patients. Thus, there is an unmet need for safe, well‐tolerated and powerful antidepressants. Poria cocos Wolf, commonly known as ‘Fu-Ling’, is a medicinal fungus and it is widely distributed in Korea, China, and East Asian countries. This fungus has long been utilized as a traditional medicine for its sedative, diuretic, and tonic effects. Recently, the sclerotia of Poria cocos were shown to have many biological activities including anticancer, anti-inflammatory, antioxidant and stabilize the mind. Therefore the main purpose of the current study was to verify whether water extract of Poria cocos conferred an antidepressant-like effect on the depressive mouse model established by forced swim test and unpredictable chronic mild stress, then explore its possible mechanism. The results shown that Poria cocos may decrease the immobility time. And the depression-related behaviors including sucrose preference test and open field test, indicated that water extract of Poria cocos 300 mg/kg can improve the depression symptoms. Western blot analysis displayed down-regulated expressions of p38 mitogen-activated protein kinase (MAPK) and decreased the expressions of tumor necrosis factor-alpha (TNF-α). Thus, it was supposed that water extract of Poria cocos might be useful for the treatment of chronic depression possibly through p38 MAPK pathway. In conclusion, we found that water extract of Poria cocos exhibited anti-inflammatory effects on depression prevention. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76560 |
DOI: | 10.6342/NTU201701996 |
全文授權: | 未授權 |
顯示於系所單位: | 食品科技研究所 |
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