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Published on: October 28, 2019
Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy
Huiqiang Wang1, Ke Li1, Linlin Ma1
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Berberine (BBR) inhibits enterovirus 71 (EV71) replication by downregulating the MEK-ERK pathway and autophagy. This natural compound shows potential as an antiviral agent against EV71 infection.
Area of Science:
- Virology
- Molecular Biology
- Pharmacology
Background:
- Enterovirus 71 (EV71) replication is significantly influenced by the MEK-ERK signaling pathway and autophagy.
- Inhibiting these pathways demonstrably impairs EV71 replication.
- Berberine (BBR), a natural alkaloid, is known to modulate both signaling pathways and autophagy.
Purpose of the Study:
- To investigate the potential of berberine (BBR) in inhibiting EV71 infection.
- To determine if BBR exerts its antiviral effects by downregulating the MEK/ERK signaling pathway and autophagy.
Main Methods:
- Antiviral effects were assessed using cytopathic effect (CPE) assays, western blotting, and qRT-PCR.
- Mechanisms of action were elucidated via western blotting and immunofluorescence assays.
Main Results:
- Berberine demonstrated a dose-dependent reduction in EV71 RNA and protein synthesis.
- This inhibition was partly attributed to the downregulation of MEK/ERK signaling pathway activation.
- Berberine suppressed EV71-induced autophagy by modulating AKT, JNK, and PI3KIII phosphorylation.
Conclusions:
- Berberine effectively inhibits EV71 replication through the downregulation of autophagy and the MEK/ERK signaling pathway.
- These findings highlight BBR as a potential therapeutic agent or supplement for managing EV71 infections.
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