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Published on: August 9, 2013
Formononetin inhibits enterovirus 71 replication by regulating COX- 2/PGE₂ expression
Huiqiang Wang1, Dajun Zhang2, Miao Ge3
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. hq_wangimb@163.com.
Background:
The activation of ERK, p38 and JNK signal cascade in host cells has been demonstrated to up-regulate of enterovirus 71 (EV71)-induced cyclooxygenase-2 (COX-2)/ prostaglandins E2 (PGE₂) expression which is essential for viral replication. So, we want to know whether a compound can inhibit EV71 infection by suppressing COX-2/PGE₂ expression.
Methods:
The antiviral effect of formononetin was determined by cytopathic effect (CPE) assay and the time course assays. The influence of formononetin for EV71 replication was determined by immunofluorescence assay, western blotting assay and qRT-PCR assay. The mechanism of the antiviral activity of formononetin was determined by western blotting assay and ELISA assay.
Results:
Formononetin could reduce EV71 RNA and protein synthesis in a dose-dependent manner. The time course assays showed that formononetin displayed significant antiviral activity both before (24 or 12 h) and after (0-6 h) EV71 inoculation in SK-N-SH cells. Formononetin was also able to prevent EV71-induced cytopathic effect (CPE) and suppress the activation of ERK, p38 and JNK signal pathways. Furthermore, formononetin could suppress the EV71-induced COX-2/PGE₂ expression. Also, formononetin exhibited similar antiviral activities against other members of Picornaviridae including coxsackievirus B2 (CVB2), coxsackievirus B3 (CVB3) and coxsackievirus B6 (CVB6).
Conclusions:
Formononetin could inhibit EV71-induced COX-2 expression and PGE₂ production via MAPKs pathway including ERK, p38 and JNK. Formononetin exhibited antiviral activities against some members of Picornaviridae. These findings suggest that formononetin could be a potential lead or supplement for the development of new anti-EV71 agents in the future.
Insights
Formononetin inhibits enterovirus 71 (EV71) replication by suppressing cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE₂) expression. This compound also shows antiviral effects against other Picornaviridae viruses.
Area of Science:
- Virology
- Molecular Biology
- Pharmacology
Background:
- Enterovirus 71 (EV71) replication is linked to host cell cyclooxygenase-2 (COX-2)/prostaglandins E2 (PGE₂) expression.
- Mitogen-activated protein kinase (MAPK) pathways, including ERK, p38, and JNK, are activated during EV71 infection.
Purpose of the Study:
- To investigate if formononetin can inhibit EV71 infection.
- To determine if formononetin suppresses EV71-induced COX-2/PGE₂ expression.
Main Methods:
- Antiviral activity assessed via cytopathic effect (CPE) and time-course assays.
- EV71 replication and viral protein/RNA synthesis evaluated using immunofluorescence, western blotting, and qRT-PCR.
- Mechanism of action explored through western blotting and ELISA assays.
Main Results:
- Formononetin reduced EV71 RNA and protein synthesis in a dose-dependent manner.
- Significant antiviral activity observed when administered before or after EV71 inoculation.
- Formononetin suppressed EV71-induced CPE, ERK, p38, JNK activation, and COX-2/PGE₂ expression.
- Antiviral effects extended to other Picornaviridae members like CVB2, CVB3, and CVB6.
Conclusions:
- Formononetin inhibits EV71 by suppressing COX-2 expression and PGE₂ production via the MAPK pathway.
- Formononetin demonstrates broad-spectrum antiviral activity against certain Picornaviridae.
- Formononetin presents potential as a therapeutic lead for anti-EV71 agents.
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