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    標題: 天然萃取物及合成物應用於預防雄性禿保養品之細胞評估
    Cell Model Evaluation of Application of Natural Product Extracts and Synthetic Compounds on Prevention of Androgenetic Alopecia
    作者: 楊雨儒
    Yu-Ju Yung
    貢獻者: 林維炤
    嘉南藥理科技大學:化妝品科技研究所
    關鍵字: 5?還原酶
    人類腎臟上皮細胞
    睪素酮
    二氫睪素酮
    dihydrotestosterone
    testosterone
    HEK293 cell
    5?reductase
    日期: 2008
    上傳時間: 2008-12-29 15:23:11 (UTC+8)
    摘要: 目前常見的男性落髮中,有95%為雄性禿患者,是經由5?還原酶(5?
    -reductase;5?R1和5?R2)此同?#37238;進行催化睪素酮 (Testosterone, T)反
    應,使得睪素酮轉換成更具效果的雄性素-二氫睪素酮(Dihydrotestosterone,
    DHT),而造成雄性禿症狀。目前臨床上已使用合成的5?reductase抑制劑
    來治療與DHT相關的疾病,並且為了能開發出更具專一性的藥物,單一同
    ?#37238;的選擇性抑制劑在醫藥的研究上代表著一項重大挑戰。在此實驗中,
    我們建立一個可信賴及方便的5?R1抑制劑的篩選平台並利用此平台來篩
    選多種中草藥萃取物和合成物。在實驗中,以女貞子、鱧腸、五倍子、菟
    絲、薑黃和扁柏共六種天然萃取物及 Compounds A、B和 C三種合成物對
    細胞進行測試。將含有人類5Ο1的cDNA(p-Flag-CMV2-5Ο1轉染至人類
    腎臟上皮細胞 (HEK293),篩選後獲得細胞株HEK293-Flag-5?R1,作為本
    實驗所使用之5?R1細胞平台;另外,本實驗室於2006年建立了5?R2細
    胞平台,以此兩個平台進行六種天然萃取物及三種合成物抑制分別5?R1
    和5?R2之能力測試。各萃取物及合成物經由MTS的測試後,各挑選細胞
    存活率在80%以上的濃度為TLC活性分析的起始濃度。由實驗結果得知,菟
    絲對於5?R1和5?R2皆有抑制的效果,女貞子及Compound A對於5?R2
    有顯著的抑制效果。
    我們所得到的結論是此平台可成正z選出5?R1和5?R2的抑制劑,
    而這些具有抑制5?reductasec活性的菟絲、女貞子、五倍子、Compound A
    及Compound B可再進一步進行動物實驗,評估未來實際應用在預防禿頭的
    保養品上。
    Hair loss is a common problem for men, and 95% of hair loss in men are
    androgenetic alopecia. 5? reductase isoenzyme (5?R1 and 5?R2 )
    catalyzes the reduction of testosterone (T) into dihydrotestosterone (DHT) , a
    very potent androgen, that cause androgenetic alopecia. A High interest has been
    paid to the synthesis of inhibitors of 5?reductase for the treatment of DHTrelated
    pathologies, and the selective inhibition of any single isoenzyme
    represents a great challenge for medical and pharmaceutical research in order to
    have more specific drugs. In this study, we attempted to establish the reliable
    and convenient screening model for 5?R1 inhibitors. Six kinds of plant
    extracts and three kinds of synthetic compounds, including Chamaecyparis
    obtusa Var. formosana extracts Curcumae Longae rhizoma extracts, Eclipta
    extracts, Nezumimochi extracts, Dodder extracts, Chinensis Galla extracts and
    Compounds A、B and C, were investigated for the inhibition of 5?R1 and 5?
    -R2 using a cell model establish here. The cell model was built up by
    transfecting a expression plasmid pFlag-CMV2-5Ο1 into HEK293, and a
    stable line was obtained and named as HEK293- Flag-5Ο1. The MTS assay
    was used to evaluate the cytotoxic effects of several plant extracts and systemic
    compounds. The maximal concentrations of these compounds with < 20%
    cytotoxic activity were chosen as the starting concentrations to assay the
    inhibitory effects on 5?reductase activity. The results showed: that Dodder、
    Nezumimochi extract 、Chinensis Galla extract、compound A and compound B
    were better inhibitors of 5Ο1 than 5Ο2.
    In conclusion, we have successfully established a cell model to assay the
    inhibitor activity of 5Ο1. We have also found some potential 5Ο1 inhibitor
    form natural products and synthetic compounds. These extracts / compounds
    might represent good lead materials to develop 5?reductase inhibitors for
    preventing androgenetic alopecia.
    關聯: 校內一年後公開,校外永不公開
    Appears in Collections:[化妝品應用與管理系(所)] 博碩士論文

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