臺灣博碩士論文加值系統

白藜蘆醇 (Resveratrol, RSV) 及短鏈脂肪酸 (Short chain fatty acid,SCFA) 分別具有抗氧化、抗發炎、抗肥胖、抗菌之能力，且可以影響不同的代謝途徑，因此本研究將白藜蘆醇與丁酸等化合物混和修飾合成白藜蘆醇丁酸酯 (Resveratrol butyrate , RBE)，並以微生物、細胞實驗模式探討了RSV、RBE對氧化三甲胺前驅物代謝之影響，微生物結果顯示，與RSV相比給予50 µg / mL濃度的RBE複合物與膽鹼誘導組相比，主要是透過強化B. longum抑制C. asparagiforme並更顯著降低三甲胺 (Trimethylamine, TMA) 的含量，RBE複合物進一步純化、鑑別並分離出五種不同結構的酯化衍生物：3,4'-二-O-丁酰白藜蘆醇 (ED2, 18.8 %)、3-O-丁酰白藜蘆醇 (ED4, 35.7 %)、4'- O-丁酰白藜蘆醇 (ED5, 4.4 %)、3,5,4'-三-O-丁酰白藜蘆醇 (ED6, 1.5 %) 和 3,5-二-O-丁酰白藜蘆醇 (ED7, 0.7 %)，其中ED2 和 ED4為主要酯化衍生物，並評估乳化液中之穩定性，結果顯示以配方一之穩定性最佳，可在不同溫度下，呈現穩定之狀態；以H2O2誘導HepG2細胞氧化壓力，預先以 RBE、ED2、ED4預處理，結果顯著可降低細胞內的ROS累積；增加GSH以及GSH/GSSG比值；以TMA誘導HepG2細胞，先以RBE、ED2、ED4預處理，與TMA組別相比可以顯著降低FMO3的基因表現，然而氧化三甲胺 (Trimethylamine-N-oxide, TMAO) 含量結果顯示，給予50 μM RBE、ED2、ED4組別上可見顯著降低TMA所誘導的TMAO含量，本研究不僅成功酯化修飾白藜蘆醇並且分離出純化物，並且證明了在微生物模式以及細胞模式中抗氧化以及調控TMA代謝相關保健功能方面的潛力。

Resveratrol (RSV) has antioxidant, anti-inflammatory, anti-obesity, and antibacterial abilities, and short-chain fatty acids (SCFA) have adjusted microbiota and influenced metabolism. For the resveratrol low bioavailability reason, resveratrol and butyric acid were synthesized by the Steglich method, and their functionality in microbial and cellular experimental models to investigate the effects of RSV and RBE (including RBE mono type derivate) The microbiological results show that compared to the choline-induced group, the administration of 50 µg/mL concentration of RBE complex in relation to RSV primarily enhances the inhibition of C. asparagiforme by B. longum and significantly reduces the levels of trimethylamine (TMA). Through purification, five esterified derivatives were identified from the RBE complex including 3,4'-di-O-butyryl resveratrol (ED2, 18.8 %), 3-O-butyryl resveratrol (ED4, 35.7 %), 4'-O-butyryl resveratrol (ED5, 4.4 %), 3,5,4'-tri-O-butyryl resveratrol (ED6, 1. 5 %) and 3. 5-Di-O-butyryl resveratrol (ED7, 0.7 %), in which ED2 and ED4 are mainly derivatives that were used to further evaluate the functional. In the emulsion analysis, the result shows formula one had the best stability at different storage temperatures. In addition, HepG2 cells induced with H2O2, then treatment with RBE complexes, ED2, and ED4, show the anti-oxidant capacity, which reduces the ROS and increases the GSH and improves the GSH/GSSG ratio. HepG2 induced with TMA then treatment with RBE complexes, ED2, ED4 can significantly reduce FMO3 in the expression of FMO3 gene, the results of the trimethylamine-N-oxide (TMAO) content study showed that 50 μM of RBE, ED2, and ED4 significantly reduced TMA-induced damage and decreased TMAO production. The present study showed that RBE could reduce TMA production in microbial mode, while RBE, ED2, and ED4 could reduce the accumulation of oxidative stress ROS induced by hydrogen peroxide and reduce produce of TMA oxidation.

摘要 I
Abstract III
誌謝 V
目錄 VII
縮寫對照表 XVI
壹、前言 1
貳、文獻回顧 3
2.1氧化三甲胺的介紹 3
2.2代謝產生三甲胺以及氧化三甲胺過程 4
2.3心血管疾病的介紹及盛行率 8
2.4氧化三甲胺與心血管疾病之相關性 10
2.5三甲胺生產菌的介紹 11
2.6益生菌的介紹 13
2.7白藜蘆醇介紹與生理功能 13
2.8短鏈脂肪酸介紹與生理功能 17
2.9修飾白藜蘆醇的介紹 20
參、研究目的 29
4.1實驗材料 32
4.2實驗儀器 32
4.3實驗藥品 33
4.4實驗設計 35
伍、實驗結果 55
5.1 RBE對於B. longum及C. asparagiforme代謝膽鹼機轉之影響 55
5.2不同乳液配方的成分配比及對藥物溶解穩定性之影響 71
5.3 RBE、ED2、ED4、H2O2對HepG2細胞株抗氧化能力之影響 81
5.4 ED2、ED4與SOD2進行分子對接 87
5.5 ED2、ED4與SOD2對接 87
5.6不同濃度TMA處理對HepG2細胞存活率之影響 92
5.7 不同濃度RBE、ED2、ED4預處理HepG2 細胞株24小時在
以4 mM TMA 處理24小時細胞存活率之影響 92
5.8 RBE、ED2、ED4與TMA處理對HepG2 細胞代謝TMA產生
TMAO含量之影響 95
5.9 TMA處理HepG2 細胞不同時間對FMO3基因表現之影響 98
5.10 RBE、ED2、ED4與TMA處理對HepG2 細胞代謝TMA基
因FMO3基因表現之影響 98
陸、討論 101
6.1 RSV、RBE對C. asparagiforme & B. longum 共培養中個別菌量
之影響 101
6.2 單一C. asparagiforme與C. asparagiforme 和 B. longum 共培
養對代謝膽鹼產生TMA含量的影響 102
6.3添加膽鹼、RSV、RBE對C. asparagiforme & B. longum共培養
下代謝產生TMA含量之影響 102
6.4白藜蘆醇酯的分離與鑑別 103
6.5不同乳化液配方的成分配比及對藥物溶解穩定性之影響 104
6.6 RBE、ED2、ED4處理對HepG2細胞株ROS生成之影響 105
6.7 RBE、ED2、ED4處理對HepG2細胞株內GSH/GSSG比率之
影響 106
6.8 RBE、ED2、ED4處理對HepG2細胞株內SOD活性之影響 108
6.9 RBE、ED2、ED4與TMA處理對HepG2細胞代謝TMA產生
TMAO含量之影響 109
6.10 RBE、ED2、ED4與TMA處理對HepG2細胞代謝TMA基因
FMO3基因表現之影響 110
陸、結論 111
柒、附錄 112
捌、參考文獻 126

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