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

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.

Berberine Induces p53-Dependent Apoptosis through Inhibition of DNA Methyltransferase3b in Hep3B Cells

“…In contrast, the protein levels of total ERK remained constant at all concentration of berberine used but the levels of P-ERK decreased at higher concentrations of berberine. The changes occurring in total ERK and P-ERK by berberine treatment was consistent with a previous report [26]. Figure 5A, B).…”

Biologically active isoquinoline alkaloids covering 2014–2018

“…centration (TC 50 ) was 73.10 μmol/L in Vero cells and the TC 50 of the positive agent pirodavir was 27.49 μmol/L 252. Corydine(90)and norisoboldine(91), aporphine alkaloids from Croton echinocarpus leaves, displayed significant in vitro anti-HIV potential.…”

Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway

“…For this reason, we made an effort to link the known activities of BBR with pathways that are important for the replication of the influenza A virus. Two recently published reports show BBR-mediated inhibition of the Chikungunya virus (CHIKV) and the enterovirus 71, which was caused by interference with the virus-induced mitogen-activated protein kinase (MAPK) signaling pathways, including extracellular signal-related kinase (ERK) [35,36]. It is also known that the active form of ERK1 (p-ERK1) is required for the nuclear export of the influenza A virus RNP complex during the infection [37] and that this pathway is modulated during the infection.…”