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.
