Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy.
Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy.
复制标题
小檗碱通过下调 MEK/ERK 信号通路和自噬抑制肠道病毒 71 复制
DOI：
10.1186/s12985-016-0674-4
复制
发表时间：
2017-01-11
期刊：
影响因子：
4.8
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wang H;Li K;Ma L;Wu S;Hu J;Yan H;Jiang J;Li Y
MEK-ERK信号通路和自噬在肠病毒71（EV71）复制中起重要作用。抑制MEK-ERK信号通路和自噬可损害EV71的复制。小檗碱（Berberine， BBR）是一种从小檗中分离出来的异喹啉生物碱，有报道称其具有调节这一信号通路和自噬的能力。在这里，我们想要确定小檗碱是否可以通过下调MEK/ERK信号通路和自噬来抑制EV71感染。方法采用细胞病变效应（CPE）法、western blotting法和qRT-PCR法检测小檗碱的抗病毒作用。采用免疫印迹法和免疫荧光法测定BBR抗病毒作用机制。结果我们发现，小檗碱确实依赖地降低了EV71 RNA和蛋白质的合成，至少部分原因是抑制了MEK/ERK信号通路的激活。此外，我们发现小檗碱通过激活AKT蛋白和抑制JNK和PI3KIII的磷酸化来抑制ev71诱导的自噬。结论bbr通过下调自噬和MEK/ERK信号通路抑制EV71的复制。这些发现提示BBR可能是对抗EV71感染的潜在药物或补充。
BackgroundThe MEK-ERK signaling pathway and autophagy play an important role for enterovirus71(EV71) replication. Inhibition of MEK-ERK signaling pathway and autophagy is shown to impair EV71 replication. Berberine (BBR), an isoquinoline alkaloid isolated fromBerberis vulgaris L., has been reported to have ability to regulate this signaling pathway and autophagy. Herein, we want to determine whether berberine can inhibit EV71 infection by downregulating the MEK/ERK signaling pathway and autophagy.MethodsThe antiviral effect of berberine was determined by cytopathic effect (CPE) assay, western blotting assay and qRT-PCR assay. The mechanism of BBR anti-virus was determined by western blotting assay and immunofluorescence assay.ResultsWe showed that berberine does-dependently reduced EV71 RNA and protein synthesis, which was, at least in part, the result of inhibition of activation of MEK/ERK signaling pathway. Furthermore, we found that berberine suppressed the EV71-induced autophagy by activating AKT protein and inhibiting the phosphorylation of JNK and PI3KIII.ConclusionsBBR inhibited EV71 replication by downregulating autophagy and MEK/ERK signaling pathway. These findings suggest that BBR may be a potential agent or supplement against EV71 infection.