Wang Huiqiang, Li Ke, Ma Linlin, Wu Shuo, Hu Jin, Yan Haiyan, Jiang Jiandong, Li Yuhuan
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Virol J. 2017 Jan 11;14(1):2. doi: 10.1186/s12985-016-0674-4.
The 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 from Berberis 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.
The 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.
We 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.
BBR 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.
MEK-ERK信号通路和自噬在肠道病毒71型（EV71）复制中起重要作用。研究表明，抑制MEK-ERK信号通路和自噬会损害EV71复制。黄连素（BBR）是从普通小檗中分离出的一种异喹啉生物碱，据报道具有调节该信号通路和自噬的能力。在此，我们想确定黄连素是否能通过下调MEK/ERK信号通路和自噬来抑制EV71感染。
通过细胞病变效应（CPE）测定、蛋白质免疫印迹分析和qRT-PCR测定来确定黄连素的抗病毒作用。通过蛋白质免疫印迹分析和免疫荧光测定来确定BBR抗病毒的机制。
我们发现黄连素剂量依赖性地降低了EV71 RNA和蛋白质的合成，这至少部分是抑制MEK/ERK信号通路激活的结果。此外，我们发现黄连素通过激活AKT蛋白并抑制JNK和PI3KIII的磷酸化来抑制EV71诱导的自噬。
BBR通过下调自噬和MEK/ERK信号通路抑制EV71复制。这些发现表明，BBR可能是一种潜在的抗EV71感染药物或补充剂。
