Purification and characterization of eugeniin as an anti-herpesvirus compound from Geum japonicum and Syzygium aromaticum.
Purification and characterization of eugeniin as an anti-herpesvirus compound from Geum japonicum and Syzygium aromaticum.
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发表时间：
1998-02
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通讯作者：
Masahiko Kurokawa;Toyoharu Hozumi;P. Basnet;Michio Nakano;Shigetoshi Kadota;Tuneo Namba;Takashi Kawana;Kimiyasu Shiraki
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作者：
Masahiko Kurokawa;Toyoharu Hozumi;P. Basnet;Michio Nakano;Shigetoshi Kadota;Tuneo Namba;Takashi Kawana;Kimiyasu Shiraki
在小鼠感染模型中，水杨梅的热水提取物显示出预防和治疗性抗单纯疱疹病毒（HSV）活性。从提取物中纯化了作为抗HSV化合物的丁香苷，并且还从另一种在小鼠中表现出抗HSV活性的草药提取物（丁香）中分离得到。因此，对丁香苷的抗HSV作用进行了表征。对于Vero细胞上的野生HSV 1型（HSV-1），丁香苷50%空斑减少的有效浓度（5.0 μ g/ml）比通过产量减少测定确定的其50%细胞毒性浓度低13.9倍。Eugeniin还抑制阿昔洛韦-膦酰乙酸抗性HSV-1、胸苷激酶缺陷型HSV-1和野生型HSV 2的生长。丁香苷以及膦酰乙酸抑制病毒DNA和晚期病毒蛋白质的合成在其感染的Vero细胞，但不细胞蛋白质的合成在其抑制浓度。纯化的HSV-1 DNA聚合酶活性被丁香苷抑制非竞争性相对于dTTP。其表观Ki值为8.2和5。8-分别比纯化的人DNA聚合酶α和β的Ki值低1倍。因此，丁香苷抑制作用的主要靶位点之一是病毒DNA合成;与抗HSV核苷类似物相比，对病毒DNA聚合酶活性的抑制作用是新颖的。
The hot-water extract of Geum japonicum has been shown to exhibit prophylactic and therapeutic anti-herpes simplex virus (HSV) activity in murine infection models. Eugeniin was purified as an anti-HSV compound from the extract and also was isolated from another herbal extract (Syzygium aromaticum) that had exhibited anti-HSV activity in mice. Thus the anti-HSV action of eugeniin was characterized. The effective concentration (5.0 microg/ml) for 50% plaque reduction of eugeniin for wild HSV type 1 (HSV-1) on Vero cells was 13.9-fold lower than its 50% cytotoxic concentration determined by a yield-reduction assay. Eugeniin also inhibited the growth of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1 and wild HSV type 2. Eugeniin as well as phosphonoacetic acid inhibited viral DNA and late viral protein syntheses in their infected Vero cells, but not cellular protein synthesis at its inhibitory concentrations. Purified HSV-1 DNA polymerase activity was inhibited by eugeniin noncompetitively with respect to dTTP. Its apparent Ki value for euginiin was 8.2- and 5. 8-fold lower than the Ki values of purified human DNA polymerases alpha and beta, respectively. Thus one of the major target sites of inhibitory action of eugeniin is viral DNA synthesis; the inhibitory action for viral DNA polymerase activity was novel compared with anti-HSV nucleoside analogs.