Wang Chunyang, Wang Peng, Chen Xiaoqing, Wang Wei, Jin Yu
School of Medicine, Nanjing University, 22 Hankou Road, Nanjing 210093, China; Nanjing Children's Hospital, Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, China.
School of Medicine, Nanjing University, 22 Hankou Road, Nanjing 210093, China; State Key Laboratory of Pharmaceutical Biotechnology and School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
Antiviral Res. 2015 Jul;119:47-56. doi: 10.1016/j.antiviral.2015.04.009. Epub 2015 Apr 24.
The aerial parts of Saururus chinensis (Lour.) Baill are a Chinese herbal medicine used for the treatment of edema and inflammatory diseases. However, the effect of this medicine on enterovirus 71 (EV71) infection has not been explored. Previous studies showed that MEK1-ERK signal pathway was required for efficient replication of EV71 infection and inhibition of this signal pathway has been shown to suppress virus infection. Here we show that the water extract of S. chinensis (Lour.) Baill (SCB) significantly blocks EV71 infection by inhibiting the activation of MEK1-ERK signal pathway with an IC50 of 8.9μg/mL. SCB at 30 and 60 μg/mL blocked EV71-induced cytopathic effect (CPE) and production of infectious virion by 1.9 and 5.1 logs, respectively. Virucidal assay suggested that SCB had no virucidal activity against EV71 and probably exerted its effect by targeting multiple steps in EV71 infection. Knockdown of MEK1 but not MEK2 blocked EV71 replication. And SCB treatment inhibited the activation of MEK1-ERK signal during EV71 infection. Furthermore, we found that rutin at 200 μM, one of the major components of SCB, significantly suppressed EV71 induced CPE and inhibited viral replication in a dose dependent manner. Taken together, SCB inhibited EV71 infection by hijacking MEK1-ERK signal pathway and rutin was the responsible antiviral component of SCB.
三白草的地上部分是一种用于治疗水肿和炎症性疾病的中草药。然而，这种药物对肠道病毒71型（EV71）感染的影响尚未得到研究。先前的研究表明，MEK1-ERK信号通路是EV71感染有效复制所必需的，并且已证明抑制该信号通路可抑制病毒感染。在此我们表明，三白草（SCB）的水提取物通过抑制MEK1-ERK信号通路的激活来显著阻断EV71感染，IC50为8.9μg/mL。30和60μg/mL的SCB分别将EV71诱导的细胞病变效应（CPE）和传染性病毒粒子的产生阻断了1.9和5.1个对数级。杀病毒试验表明，SCB对EV71没有杀病毒活性，可能是通过靶向EV71感染的多个步骤发挥其作用。敲低MEK1而非MEK2可阻断EV71复制。并且SCB处理抑制了EV71感染期间MEK1-ERK信号的激活。此外，我们发现200μM的芦丁（SCB的主要成分之一）以剂量依赖的方式显著抑制EV71诱导的CPE并抑制病毒复制。综上所述，SCB通过劫持MEK1-ERK信号通路抑制EV71感染，芦丁是SCB中起作用的抗病毒成分。
