龍眼花水萃物對於腦部與腸道菌相抗憂鬱作用機轉之探討

Abstract

憂鬱症是目前全球最常見的精神疾病，也是導致失能的主要原因。根據世界衛生組織 (WHO) 統計，目前約有2.8億人患有憂鬱症，其中，臺灣憂鬱症盛行率甚至為全球2倍之多，對於憂鬱症的預防更是當務之急。憂鬱症有多種可能病理機制，如：單胺理論、下視丘-腦下垂體-腎上腺軸 (HPA axis) 以及腸腦軸線 (gut-brain axis)，並且會導致多種症狀，包括：情緒低落、失去對事物的興趣、負面想法等。目前，憂鬱症主要治療方法是使用抗憂鬱藥物，但這些藥物伴隨不少副作用，因此，近年來具有抗憂鬱作用的天然產物成為新興輔助治療方式。龍眼是臺灣種植面積第五大的經濟作物，是重要的農作物之一，而農業試驗所在2019年時發現龍眼的花朵中含有具抗憂鬱潛力的天然分子。先前研究表明，龍眼花水萃物不僅可以提高類帕金森氏症疾病大鼠大腦紋狀體中的多巴胺含量，還有神經保護和抗氧化作用；另一研究表明，龍眼花水萃物可以顯著提高血清素和褪黑激素濃度及相關基因表現，從而緩解失眠症狀。然而，目前尚無已發表的文獻探討龍眼花水萃取物與憂鬱症之間的關係。因此，本研究旨在探討龍眼花萃取物在不可預期慢性溫和壓力 (unpredictable chronic mild stress, UCMS) 誘導大鼠產生憂鬱症狀的動物模型中的抗憂鬱作用及其機制。實驗結果發現，龍眼花水萃物可以降低血清中壓力因子皮質酮、前額葉皮質促發炎細胞因子濃度和單胺類神經傳導物質之轉換率來改善大鼠的憂鬱行為。此外，龍眼花水萃物也能影響大鼠的腸道菌相的組成，並形成特定優勢菌種如鼠乳酸桿菌 (Ligilactobacillus murinus)，這些菌種可能發揮抗憂鬱的輔助作用。總結來說，龍眼花水萃物可改善UCMS大鼠的憂鬱症狀，並可能是透過多種機制達到抗憂鬱效果。本研究成果為利用天然物治療及預防憂鬱症提供另一想法，並期待不同作用機制或臨床應用之探討，作為保健產品開發之科學參考依據。

Depression is currently the most prevalent mental illness and a major cause of disability worldwide. According to the World Health Organization (WHO), it is estimated that 280 million people suffered from depression in 2023. In Taiwan, the prevalence rate is 8.9%, which is nearly twice the global average. These figures highlight the critical importance of strategies for preventing depression. Various factors contribute to the progression and pathology of depression, such as the monoamine theory, the hypothalamic-pituitary-adrenal axis, and the gut-brain axis, leading to several symptoms, including depressed mood, diminished interest, and negative thinking, and so on. The primary treatment for depression is antidepressants; however, the medications may have side effects. Therefore, alternative approaches, especially natural products with anti-depression effects, are crucial in alleviating depression. Longan is one of the important economic crops in Taiwan. Its flower was recently observed to contain natural molecules with antidepressant potential by the Taiwan Agricultural Research Institute. A previous study demonstrated that Longan flower water extract (LFWE) could not only raise dopamine content in the striatum but also had neuroprotection and antioxidation effects in rats with Parkinson's-like disease, which shares some common pathological mechanisms with depression. Another study showed that LFWE could significantly raise serotonin and melatonin levels to relieve insomnia. Nevertheless, no published papers have examined the relationship between LFWE and depression. Consequently, our study aims to investigate the anti-depression effects and mechanisms of Longan flower water extract in the unpredictable chronic mild stress (UCMS)-induced rat depression model. In the experimental results, we found that LFWE could improve depression-like behaviors through lowering corticosterone, pro-inflammatory cytokines, and the turnover rate of monoamines. Furthermore, LFWE could affect the composition of gut microbiota and lead to specific dominant species, such as Ligilactobacillus murinus, considered to play a role in anti-depression. In conclusion, LFWE might have an anti-depression effect via multiple mechanisms. The outcome of the research could pave the way for using natural products in treating and preventing depression. Further investigations into the underlying mechanisms and clinical trials are warranted to support the development of functional foods.