Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy

Huiqiang Wang,Linlin Ma,Yuhuan Li,Ke Li,Shuo Wu,Haiyan Yan,Jin Hu,Jiandong Jiang

doi:10.1186/s12985-016-0674-4

Huiqiang Wang, Linlin Ma + Show 6 more

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https://doi.org/10.1186/s12985-016-0674-4

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Abstract

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 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.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.

Highlights

The MEK-ERK signaling pathway and autophagy play an important role for enterovirus71(EV71) replication
Deng et al demonstrated that BBR attenuates autophagy in adipocytes by targeting BECN1 [25]. These findings suggest that BBR can regulate MEK/ERK signaling pathway and autophagy, which implies that BBR might be effective in limiting viral replication
We first detected the toxicity of BBR and pirodavir in viruses African green monkey kidney (Vero) cells by Cell Counting Kit (CCK) assay (Fig.1c, d)

Summary

Introduction

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. We want to determine whether berberine can inhibit EV71 infection by downregulating the MEK/ERK signaling pathway and autophagy. Enterovirus, which belongs to the Picornaviridae family, is often associated with a serious infectious disease affecting millions of people worldwide. Enterovirus 71 (EV71) is the most common cause for hand, foot and mouth disease (HFMD) in children under the age of five [1]. EV71-caused HFMD is often associated with severe neurological diseases and fatalities. Currently there are no effective antiviral drugs in the clinic to treat EV71-induced HFMD [2, 3]

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