以代謝體研究法探討薑黃影響糖尿病前期工作記憶之生物標記與潛在機制

Application of metabolomics approach to find biomarkers and mechanisms of turmeric effect on working memory in pre-diabetes

吳豐如(Feng-Ju Wu)

指導教授 ： 潘文涵

國立臺灣大學/生命科學院/生化科技學系/碩士(2016年)

https://doi.org/10.6342/NTU201603520

摘要

研究背景與目的：過去研究團隊發現，攝取薑黃 6 小時內能改善認知功能及增進工作記憶。然而薑黃對於工作記憶的影響並不是透過降血糖途徑或降低阿茲海默症相關生物標記基因表現量而來，因此需要更進一步的研究來了解其影響機制。代謝體學主要的標的物為生物體內的小分子代謝物，藉由測量這些代謝物，能夠幫助我們更加清楚人體代謝受到挑戰時的變化情形。本研究接續之前的相關短期攝食研究，利用代謝體學的方式探討薑黃組與安慰劑組血漿中代謝物的變化型態之不同，進而搜尋可能參與工作記憶的生物指標、代謝路徑和機制。
實驗方法：本研究前一階段招募 23 位受試者，為一隨機分派雙盲的代謝體研究。投予薑黃後，試驗觀察期大約為 6 小時。本研究測量評估試驗前以及試驗後固定時間點 (2,4,6小時後)，個案血中代謝物強度，並與工作記憶分數利用廣義估計方程（GEE）模型比較薑黃組與安慰劑組之平均測量值與變化斜率差異作關聯分析。實驗組 (n=12) 攝入兩片白吐司以及薑黃膠囊 (1g) ，安慰劑組 (n=11) 作為對照組，共進行 4 個時間點的血漿樣本收集。所有樣本使用全方位的分析平台：超高效液相層析四極柱飛行時間質譜儀來分析安慰劑組和攝食薑黃組的血漿樣本。
結果：有顯著差異的代謝物在人體參與的代謝路徑包含碳水化合物代謝、氨基酸代謝、核酸代謝、脂質代謝等。此外，我們發現 S-Adenosyl-L-homocysteine (負向) 和 trans-Cinnamic acid (正向) 這兩個代謝物和受試者工作記憶分數的改善量顯著相關。這些發現提供了一個全面的血漿代謝圖譜，有助於探討攝取薑黃能夠增進工作記憶的潛在機制。
結論：由實驗結果發現，薑黃可能作用機制為提升苯丙氨酸代謝及降低半胱氨酸和腺苷代謝以提升工作記憶。本實驗結果幫助我們更加了解薑黃增進工作記憶的作用機制。

關鍵字

代謝體學 ； 血漿 ； 薑黃 ； 工作記憶

並列摘要

Background and objective: Our previous study showed that the intake of turmeric with white bread could acutely increase working memory in patient with prediabetes. However, the effect was not associated with known AD biomarkers, more research is needed to understand the potential mechanisms. Metabolomics is a systematic platform which appraises all small molecule metabolites in a bio-specimen. Exploring metabolomics changes may help us to find new biomarkers and mechanisms associating with working memory. This study was a double-blind randomized placebo controlled metabolics study. We intended to use analytical metabolomics approach to find specific metabolic changes associated with turmeric intervention.
Method: The study included 2 groups: the experimental group (n=12) provided with 1g of turmeric capsule and with two slices of bread, whereas the control group (n=11) provided with placebo. The observation period lasted for 6 hours collecting the plasma samples at four time points and appraising working memory (WM) before and after the 6 hr period. We applied a comprehensive UPLC-MS platform to carry out untargeted plasma metabolomics. Using generalized estimating equation (GEE) models, we carried out statistical analyses to compare turmeric groups with placebo group through time points on mean intensity difference and on slope of intensity changes.
Results: Metabolite markers identified were involved in carbohydrate metabolism, amino acid metabolism, nucleotide metabolism, lipid metabolism, etc. The changes (AUC) of S-adenosyl-L-homocysteine was inversely associated with WM changes; whereas trans-cinnamic acid was found positively associated with WM changes. These findings provide a comprehensive global plasma metabolite profiling and may contribute to understanding the pathogenic mechanism of how turmeric improved WM performance.
Conclusion: In conclusion, we identified comprehensive metabolic shifts between turmeric and placebo subjects including altered carbohydrate metabolism, nucleotide metabolism, lipid metabolism, amino acid metabolism, etc. The WM improved by turmeric administration may on account of changes in cysteine and adenosine metabolism as well as phenylalanine metabolism identified in our study. This study helps us approach the potential mechanism of turmeric effect on working memory.

並列關鍵字

metabolomics ； plasma ； turmeric ； working memory

參考文獻

49. Lee, M.-S., et al., Turmeric improves post-prandial working memory in pre-diabetes independent of insulin. Asia Pacific journal of clinical nutrition, 2014. 23(4): 581.

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