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博碩士論文 etd-0716113-162938 詳細資訊
Title page for etd-0716113-162938
論文名稱
Title
具抗發炎活性之海洋天然衍生物應用於藥粧品活性研究
An anti-inflammatory activity of marine-derived compound for cosmeceutical use
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
89
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2013-07-17
繳交日期
Date of Submission
2013-08-19
關鍵字
Keywords
斑馬魚、黑色素、抑制黑色素生成、酪胺酸酶、抗發炎
melanin, anti-inflammatory, anti-melanogenic, zebrafish, tyrosinase
統計
Statistics
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中文摘要
大多數亞洲人認為白皙的皮膚,是美麗的象徵,根據Euromonitor International市場統計,在2012年,全球化妝品市場市場超過4300億美元。有一些化妝品上的使用不僅是為了外觀美麗,如被稱為「藥粧品」則是具有明確的功能或作用機制能舒緩皮膚的狀況。例如,發生發炎反應通常伴隨著與黑色素生成與沉澱,並引起皮膚不適症狀,如接觸性皮膚炎,特應性皮膚炎,或由於暴露於紫外線的皮膚損傷產生相關疾病。現今市面廣泛使用的美白劑,如對苯二酚,熊果素具有毒性,使用上仍有其局限性。我們初步透過小鼠巨噬細胞樣RAW264.7細胞進行抗發炎篩選,來自一海洋天然衍生物(marine-derived compound)顯著抑制經脂多醣誘發的促發炎蛋白──iNOS的表現量。本研究希望找到功效性和安全性更好的化合物,不僅具有抗發炎,降低黑色素生成或其他特性,未來應用於藥粧或醫療用途。研究結果顯示,海洋天然衍生物能有效地抑制黑色素含量,經由抑制酪胺酸酶活性,且在低濃度下並不具毒殺作用。而在斑馬魚模式中,持續給予低濃度海洋天然衍生物,亦可持續降低其體色表現,而不會產生毒副作用。我們在離體和活體的檢測結果發現,此來自海洋的化合物海洋天然衍生物具有抗發炎、抑制黑色素生成及抗氧化作用,未來應用於美容醫學將有無限潛力。
Abstract
Most Asians consider fair skin to be a key element of beauty. According to market statistics (source: Euromonitor International), in 2012, cosmetics accounted for a revenue of more than $430 billion in global markets. Some of these cosmetics are used for purposes other than beauty; ‘cosmeceutical’ applications can be utilized for functions or mechanisms to soothe skin conditions. For example: postinflammatory hyperpigmentation, which usually accompanies disorders associated with melanogenesis, is caused by dermatological diseases such as contact dermatitis and atopic dermatitis or by skin damage due to UV exposure. Some of the widely used skin-whitening agents in cosmetic products or for hyperpigmentation diseases, such as hydroquinone and arbutin, are toxic and, hence, have their limitations. Findings of our preliminary anti-inflammatory screening procedure showed that a marine-derived compound significantly inhibited the expression of lipopolysaccharide-induced proinflammatory protein iNOS in murine macrophage-like RAW264.7 cells. The aim of this study was to find a safer and more effective compound than those currently in use, with anti-inflammatory, anti-melanogenic or other applicable properties for future cosmeceutical or medical use. Our results indicated that the marine-derived compound could effectively inhibit pigmentation likely by the potential downregulation of tyrosinase activity; furthermore, the compound also demonstrated low cytotoxic effect dose on B16-F10 murine melanoma cells. We also found that the marine-derived compound could suppress melanin formation while sustaining delivery treatment in the zebrafish model, without having any toxic effects. Results of our in vitro and in vivo biological assays showed that the synthetic marine-derived compound possesses anti-inflammatory, anti-melanogenic and anti-oxidative properties, with potential application in medical cosmetology.
目次 Table of Contents
目錄
論文審定書………………………………………………………….……...……………i
誌謝…………………………………………………………………………..………….ii
中文摘要…………………………………………………………………….………….iii
英文摘要……………………………………………………………………….……….iv
第一章 前言………………………………………………………………….…...…...1
     美容藥粧保養品市場廣大…………………………………………....…...1
     美容藥粧保養品產業之潛在危機…………………….…………….….....1
     海洋天然物之研發利基…………………………………………....……...2
     人體皮膚系統之生理構造與功能………………………………………....5
     人體膚色的成因………………………………………...…...…...…..…...7
     人體內黑色素生成機制………………………………...………….……...7
     普遍美白治療策略與疑慮……………………………...………………..12
     現今研發美白活性之分析模式與瓶頸……………………………...…..13
     新興斑馬魚活體模式之應用…………………………...………………..14
     斑馬魚應用於美白活性分析之利基…………………………...………..15
     其他藥妝品活性分析………………………………...……….…..……..16
     本研究之動機與目的………………………………...……….......…….18
第二章 材料與方法…………………….…………………………………………..…20
     離體抗發炎活性篩選…………………………………………….…….…20
     離體細胞毒殺檢測………………………………….………………….…21
     離體細胞美白活性分析………………………………………….......…..22
     活體斑馬魚美白活性分析………………………………….……...….....23
     蘑菇酪胺酸酶酵素抑制動力學分析……………………………………..26
     分子對接模擬配基與蛋白質交互作用…………………………………..26
     DPPH自由基清除之抗氧化能力………………………………….……..26
     離體細胞之遷移作用……………………………………………....……..26
     離體細胞之抗光老化作用………………………………………….…….27
     實驗數據統計分析…………………………………………….…...……..27
第三章 實驗結果…………………………………………………….………………28
     MRX具抗發炎活性……………………………....…………………......…28
     不同濃度之MRX對細胞存活率影響……….…...…………………....…..28
     MRX能影響B16-F10細胞之黑色素表現量及酪胺酸酶活性……….......29
     MRX能降低斑馬魚體色之像素訊號…………………………………......29
     MRX能降低斑馬魚之黑色素含量及酪胺酸酶活性...…………...………30
     MRX對於活體斑馬魚之安全性評估………….……………………….....30
     持續觀察MRX對於斑馬魚體色深淺變化之影響………………....……..30
     MRX對於黑色素生成相關蛋白之影響……….………….………....……32
     MRX對於黑色素小體之影響………………….………….………....……33
     MRX對於酪胺酸酶抑制作用之機制…….………….……….………...…34
     MRX具抗氧化(anti-oxidation)活性………………….……….………..…34
     MRX對於細胞遷移(cell migration)之影響………….……….……..……35
     MRX對於光老化(photoaging)之影響……………….……….……..……35
第四章 討論……………………………………………….………………………....62
參考文獻…………………………………………………………………………...........67
附錄……………………………....…………………………………….………...…...…75
簡歷…………………………………....…………………………………….………...…78
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