魚油在癌症臨床應用及其酯化EGCG產物之研究

癌症患者在化放療期間或治療後經常會有營養不良、惡病質和疲勞等問題。適當的營養支持可以保持良好的狀態。魚油主要由ω−3脂肪酸組成，如二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），被認為是有益健康的成分。綠茶富含兒茶素，具有各種生物活性，但其生物利用率很低。臨床研究顯示，ω−3多元不飽和脂肪酸有助於改善癌症患者的病況，並促進營養素的吸收。本研究擬了解EGCG與富含EPA和DHA魚油之酯化物和EGCG-魚油混合物在腸道細胞上的生物活性。因此，主要分以兩部分進行：一、魚油在癌症臨床應用本臨床試驗使用癌症營養配方 - Protison TM（PCNF；富含 ω-3 FA、纖維、BCAA 和微量營養素），針對各種癌症患者之營養改善進行影響評估，招募了採鼻餵管、胃造口及腸造口之灌食方式共42位營養狀況不佳的癌症患者，每天給予5-6罐的PCNF (237 mL/Pack)，並持續 12 週。受試者使用 PCNF 後，總熱量的攝取、體重及BMI 均有顯著的增加（p<0.001）。此外，血漿總蛋白、前白蛋白和運鐵蛋白的含量也顯著提高（p<0.007）。本結果顯示，使用PCNF 可以顯著改善患者的營養狀況。二、魚油在酯化EGCG後提高EGCG生物利用率之研究 EGCG 和 DHA/EPA（魚油）酯化/混合物透過薄層色譜（TLC）、高性能液相層析（HPLC）、核磁共振（NMR）和氣相色譜-品質譜儀（GC-MS）加以確認後進行抗氧化、抗糖化及生物利用率分析。結果顯示，魚油之EGCG酯化物在TEAC及DPPH清除能力試驗中皆顯著高於EGCG及EGCG-魚油混合物，抗醣化能力試驗則不及EGCG。在腸道細胞吸收試驗中，相較於EGCG組，EGCG酯化物組在24小時及48小時的吸收率均有顯著性提升，分別為18.73%和20.74%。此外，與EGCG-魚油混合物相比，由魚油之 EGCG酯化物能顯著抑制腸道上皮細胞中糖化終產物（AGEs）的生成。

關鍵字

癌症；營養狀態；管灌；兒茶素；酯化；生物利用率

並列摘要

Cancer patients often encounter various health issues like malnutrition, cachexia, and fatigue during or after chemotherapy. Hence, they need balanced nutritional support (nutraceuticals and dietary supplements) to maintain optimal health status. Fish oil is primarily composed of omega-3-fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are considered as major ingredients responsible for various health benefits1. Green tea is rich in epigallocatechin gallate (EGCG), which is responsible for various biological functions, but its bioavailability is limited. Clinical researches indicate that omega-3 polyunsaturated fatty acids could improve the inflammation of cancer patients and promote the absorption of nutrients. The objective of the present study was to check the beneficial efficacy of EGCG esterified with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil (ester derivatives) and EGCG-Fish oil complex on C2BBe1 cells.Hence, we divided our study into two parts: PART I. Study on the cancer clinical application of fish oil. Current clinical trial was designed to examine the impact of balanced nutritional formula- ProtisonTM cancer nutritional formula (PCNF; enriched with ω-3 FA, fibers, BCAA, and micro-nutrients), in various cancer patient by checking calorie intake and overall health status. Totally 42 cancer patients with poor nutritional status under nasogastric (NG) tube feeding was recruited and administered with the commercial nutritional formula (PCNF; 237 mL/Pack) for 5-6 times/day via bolus NG tube feeding for 12 weeks. Subjects administered with PCNF showed a significant increase (p< 0.001) in calorie intake and increased body weight, BMI. Also, the levels of total proteins, pre-albumin, and transferrin were also significantly increased (p< 0.007) in PCNF supplemented patients. Moreover, PCNF fed cancer subjects showed normal range of various biochemical parameters like glycemic indices, lipid profile and various biochemical markers with improved nutritional status. Taking together that PCNF tube-fed cancer patients showed better health status (lower the risk of malnutrition and cachexia) by improving body weight, BMI, protein, and pre-albumin without any adverse effects. PART II. Enhanced bioavailability of EGCG after esterification with fish oil. The EGCG and DHA/EPA (fish oil) esterification/complexation was confirmed by various techniques including thin-layer chromatography (TLC), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and gas chromatography-Mass spectrometry (GC-MS) as well as antioxidant and antiglycation activity was checked using 3 different experimental samples (EGCG, EGCG-ester and EGCG-Fish oil complex). The antioxidant activity (TEAC, DPPH scavenging activity) of EGCG-ester (DHA/EPA) was significantly higher (p<0.05) than the EGCG-fish oil complex and EGCG alone group. In the cell model, both EGCG-ester (DHA/EPA) and EGCG-Fish oil complex did not show any significant changes in viability (cytotoxicity) with no morphological changes and thus implication its safety. The best EGCG permeability coefficient (cell uptake) was observed in EGCG-ester (DHA/EPA) group at 24 hrs (18.73%) and 48 hrs (20.74 %) as compared to the EGCG-Fish oil complex and EGCG alone. Also, EGCG-ester (DHA/EPA) ester showed good anti-glycation activity by significantly inhibiting (p<0.05) the advanced glycation end products (AGEs) production (BSA-MGO, BSA-Fructose) in C2BBe1 cells as compared to the EGCG-Fish oil complex group. Overall, current study indicates that EGCG-ester (DHA/EPA) showed potent antioxidant activity by improving EGCG bioavailability (cellular uptake) and followed by the improved anti-glycation property through inhibiting AGEs production.

並列關鍵字

Cancer ； nutritional status ； tube feeding ； EGCG ； esterification ； bioavailability

參考文獻

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魚油在癌症臨床應用及其酯化EGCG產物之研究

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