2016-01-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/702643摘要：橘皮中萃取的活性化合物具有預防退化型疾病的生物功效，如：心血管疾病、慢性發炎、糖尿病、癌症等問題。從橘子皮萃取分離而來之具生物活性的化合物已被分類為黃酮的亞組，稱：多甲氧基黃酮(PMF)。PMF在高溫下為疏水性並且能維持其晶體結構，從而導致較低的口服生物可利用率且造成食品加工上的一大挑戰。在這個計畫中，我們將開發一個新型的粉狀微乳化系統來包覆橘皮萃取物以增加其口服生物可利用率繼而提升其預防非酒精性脂肪肝發展的功效。 這個計劃將分為三年執行。在第一年期間，我們將透過科學系統化的方式來選擇出最適合的組成材料及加工參數來製備粉狀微乳化系統，並利用科學儀器來研究微乳化系統的化學及物理特性。在完成PMF之粉狀微乳化系統的開發後，第二年及第三年將會分別把重點專注在評估粉狀微乳化系統在調節橘皮萃取物之活性物質的口服生物可利用率及其在生物體內對於疾病預防的功能性效果。我們將透過體外胃腸模式和體內藥物動力學研究來評估粉狀微乳化系統對於橘皮活性物質在生物系統內的消化、吸收、代謝及分配等過程。第三年將進一步利用細胞實驗探討橘皮萃取物在抑制胞內脂質堆積並搭配高脂飲食誘發的非酒精性脂肪肝動物模式，評估粉狀微乳化系統在改善橘皮萃取物的劑量效率和疾病預防的功效。 <br> Abstract: Bioactive compounds in orange peel extract were widely researched for their ability to prevent the development of degenerative diseases, such as cardiovascular diseases, chronic inflammation, diabetes, cancer, and etc. The bioactive compounds in the orange peel extract were identified and categorized into the subgroup of flavone called polymethoxyflavone (PMF). This group of bioactive compounds has a benzo-γ-pyrone (15-carbon, C6–C3–C6) skeleton with a carbonyl group at the C4&#160;position. As result of its chemical structure, PMFs are hydrophobic and maintain crystalline structure at high temperature, which leads to poor oral bioavailability and big challenges in food processing. In this work we propose to develop a powdered microemulsion system to encapsulated orange peel extract (rich in PMFs) aiming to enhance its oral bioavailability and efficacy to prevent the development of non-alcoholic fatty liver. This project will be executed in three consecutive years. During the first year, the powdered microemulsion system will be developed from optimized material selection, processing parameters, and orange peel extract loading efficiency. Chemical and physical properties of the microemulsion system will be evaluated using well-established analytical methods including chromatography profiling, light scattering detection, and microscopic observations. Following the development of powdered microemulsion system, second and third year will shift the focus to evaluated the functionality of such system in the biological environment in terms of regulating the oral bioavailability and efficacy of orange peel extract. The effects of powdered microemulsion system on the oral bioavailability of orange peel bioactives will be evaluated using series of in vitro gastrointestinal models and in vivo pharmacokinetic study, which in combination allows a mechanistic elucidation of critical factors that contribute to the digestion, absorption, metabolism, and distribution process in the biological system. After studying the factors affecting the oral bioavailability, the third year will further examine the ability of powder microemulsion system to improve the dosage efficiency and efficacy of orange peel extract when used to prevent the development of non-alcoholic fatty liver diseases induced by consumption of high fat diet. In this part of work, in vitro cell line model studying the intracellular lipid accumulation will be conducted in addition to the animal model for better elucidation of the role of orange peel extract in the disease generative process. The expression protein biomarkers and serum lipid profile related to non-alcoholic fatty liver will be quantified as evidence of disease progression. In summery, the work proposed in this work will be a through study to examine the effectiveness of powder microencapsulation system to regulate the bioavailability and efficacy of bioactive ingredient. From the formulation development to the biological modeling, this work not only will demonstrate the usefulness of powdered microemulsion system but also will serve as great analytical reference for future investigators who would like to develop effective formulation targeting oral consumption route.橘皮萃取物奈米乳液非酒精性脂肪肝粉末型微乳球口服生物利用率藥物代謝動力學orange peel extractnanoemulsionnon-alcoholic fatty liverpowdered nanoemulsionoral bioavailabilitypharmacokinetic