茯苓與蟲草米複方萃取物於不可預期慢性溫和壓力動物模式中抗憂鬱及抗焦慮之功效

Abstract

根據世界衛生組織的統計，全球有超過 3 億人口罹患憂鬱症，且預測在 2030 年憂鬱症將成為全球負擔性疾病首位。而心理疾患往往不是單一發生的，研究指出，有超過 50% 的重鬱症患者同時患有焦慮症，憂鬱與焦慮對患者生活品質的影響及社會成本的負擔，已不容忽視。由於抗憂鬱、抗焦慮藥物之副作用，僅有 50% 以下的患者接受適當治療，因此愈來愈多研究希望透過日常飲食達到預防疾病的目的，並以中草藥作為材料開發抗憂鬱之保健食品。茯苓 (Poria cocos, PC) 在中醫記載中有利尿、健脾及鎮靜等效果。蟲草米 (Cordyceps militaris rice, CMR) 為培養北冬蟲夏草子實體之固態基質，同樣含有北蟲草的主要活性成分蟲草素。文獻指出兩者皆能抑制發炎反應，且具有抗憂鬱的效果。本研究採用不可預期慢性溫和壓力 (unpredictable chronic mild stress, UCMS) 模式誘發大鼠類憂鬱及類焦慮行為，探討茯苓與蟲草米複方萃取物 (Poria cocos and Cordyceps militaris rice extract formula, PC-CMR) 是否具有抗憂鬱及抗焦慮之功效。結果顯示 PC-CMR 可以改善 UCMS 造成之體重、攝食量、飲水量下降，並提升大鼠 30% 蔗糖水偏好程度及高腳十字迷宮中待在開放臂的時間。分析大鼠腦部神經傳導物質濃度，發現 PC-CMR 可以降低大鼠前額皮質、海馬迴中神經傳導物質代謝率及杏仁核中麩胺酸的濃度，抑制興奮性神經毒性。以酵素連結免疫吸附分析法及西方墨點法分析發炎反應相關路徑，PC-CMR 可以降低血清中促發炎細胞因子的濃度，顯著減少前額皮質中 35% 有絲分裂活化蛋白質激酶 (mitogen-activated protein kinase, MAPK) 磷酸化程度及 50% 核因子活化B细胞κ輕鏈增強子 (nuclear factor kappa-light-chain-enhancer of activated B cells, NF-κB) 磷酸化程度，顯著降低杏仁核中信號轉導及轉錄激活蛋白3 (signal transducer and activator of transcription 3, STAT3) 磷酸化程度及吲哚胺2,3-雙加氧酶 (indoleamine 2,3-dioxygenase, IDO) 35% 的表現量。綜合上述結果，PC-CMR 可藉由降低發炎反應、維持神經傳導物質平衡達到抗憂鬱及抗焦慮之功效。

According to WHO, over 300 million people suffered from depression, and depression is predicted to become the first place of global burden disease in 2030. There are more than fifty percent of patients with major depressive disorder also suffering from anxiety disorder. However, because of the side effects of the antidepressants and anxiolytics, less than half of the patients get appropriate treatments. Therefore, more and more research used Chinese herbal medicine as sample to find complementary therapies. Poria cocos (PC) is a medicinal fungus and long been used as traditional medicine for its sedative, diuretic and tonic effects. Cordyceps militaris rice (CMR) is the matrix for solid state culture of Cordyceps militaris. CMR also contains cordycepin as Cordyceps militaris. Previous research indicated that both PC and CMR possess anti-inflammation activity and antiepressive effect. In this study, we used unpredictable chronic mild stress (UCMS) to induce depressive-like and anxiety-like behaviors in rats, and to investigate whether Poria cocos and Cordyceps militaris rice extract formula (PC-CMR) possesses antidepressive and anxiolytic effects. The results showed that PC-CMR could reverse the loss of body weight, food intake, water intake and sucrose preference induced by UCMS. It was also observed that PC-CMR increased the time rats spent in open arm in elevated plus maze. PC-CMR significantly reduced glutamate and the metabolic rate of serotonin (5-HT) and dopamine (DA). Investigating inflammation-related pathway, PC-CMR decreased the proinflammatory cytokines in serum and displayed down-regulated expression of p38 mitogen-activated protein kinase (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ,signal transducer and activator of transcription 3 (STAT3) and indoleamine 2,3-dioxygenase (IDO). In conclusion, PC-CMR possessed antidepressive and anxiolytic effects via modulating neurotransmitters and reducing inflammation.