抗病毒藥材之研究第三報 天然多酚類及森氏楊桐抗病毒活性成分

Studies of Antiviral Drug(3) The Antiviral Effects of Natural Polyphenolic Compounds and the Components of Cleyera japonica Thunb. var morii(Yamamoto) Masamune

沈里彥(Lee-Yen Shen)

指導教授 ： 顏焜熒 ； 楊玲玲

臺北醫學大學/藥學院/生藥學研究所/碩士(1995年)

摘要

1981年發現後天性免疫缺乏症候群(Acquired Imunodeficiency syndrome)係由人類免疫缺乏病毒(Human Immunodeficiency Virus(HIV))所引起，臺灣地區從1984年發現第一位病例以來，十年間帶原者增加到了七百多人。Epstein-Barr virus(EBV)為一種嗜人類B淋巴細胞的herpes virus，與盛行於中國東南沿海及臺灣的未分化鼻咽癌(nasopharyngeal carcinoma)有密切的關聯。由於此兩種病毒對國人有重大的影響，故以EBV DNA polymerase(EBV DP)之活性，及受HIV慢性感染之ACH2及可被HIV感染之Sup T1細胞株為指標，進行抗病毒藥物的研究。 近年來藥理學方面的研究證實多酚類化合物具有抑制腫瘤的增長，抑制致癌物引起的腫瘤，及抗病毒(如HIV，HSV...)等作用；在我們篩選的43種鞣質中，對EBV DP於濃度等於10ng/ml時抑制率可達80%以上者有10種，其中以euphorbin B之IC50最低可達5.48μg/ml。但其與α-DNA polymerase之抑制率比較則濃度似乎太過相近，對此兩種去氧核醣核酸聚合酵素之IC50而言，大部分之比率均近或小於1，故其抑制之機轉應是有再探討之價值。至於對HIV的作用，列明顯可看出細胞毒性大。 本實驗由森氏楊桐所分離出之九種化合物，Compound2為quercitrin，Comnpound 5-9分別為(+)catechin,ellagic acid,gallic acid, quercetin, β-sitosterol, Compound 1,3,4因為分離出之量不足，故有待來日冉付大量分離，以確定其結構；以上九種化合物對EBVDP之抑制率以comnpound4最好，於5μg/ml時仍有90%。

關鍵字

天然多酚類 ； 森氏楊桐

並列摘要

The acquired immunodeficiency syndrome (AIDS) which was caused by Human Immunodeficiency Virus (HIV) was found in 1981. In Taiwan the first AIDS case was reported in 1984 and the infected patients were increasing to more than seven thundreds in a decade. The Epstein-Barr virus is a human B lymphotropic herpes virus. This virus was found closely associated with undifferentiated nasopharyngeal carcinoma, which is epidemic in Southeastern China, Taiwan, and North Africa. Since these two viruses have great influence on the people living on Taiwan, to facilitate the discovery of antinasopharyngeal carcinoma drugs, the inhibitory effect of Epstrin-Barr virus DNA polymerase and Sup Tl cell line which was infected by the HIV chronic infected ACH 2 cell line were used as indexes to screen the antivirial drugs. The polyphenolic compounds have many kinds of pharmacological activities such as antiviral activity, inhibiting growth of the cancer cells, and preventing the occurrence of tumor which were induced by carcinogens. In the forty-three chosen tannins there are ten tannins which in 10 μg/ml have more than 80% inhibition percentage to EBV DNA polymerase. But compared to the IC30 of α-DNA polymerase, the inhibition contrations of EBV DNA polymerase and ex-DNA polymerase are too close. Most ratios of both 1030 to EBV. DNA polymerase and to (α-DNA polymerase are close to or less than I, so the inhibition machanism of the ten tannins is still left to be investigated in the future. To HIV the inhibition of the 43 drugs is not clear but all cytotoxic. We have separated nine compounds from the extraction of Cleyera japonica Thunb. var. morii. Compound 2 is quercitrin. Others from compound 5 to 9 are (+)catechin, ellagic acid, gallic acid, quercetin, β-sitosterol. The other structures are not determined because the gained quantity are not enough to analysis. Amoung these compounds the best inhibition to EBV DP is compound 4 when in 5 μ g/ml the inhibition percentage is 90%.