Abstract
BackgroundThe 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.MethodsThe 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.ResultsFormononetin 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).ConclusionsFormononetin 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.
Highlights
The activation of ERK, p38 and Jun-N terminal kinase (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
These results demonstrated that formononetin can significantly inhibit the replication of Enterovirus 71 (EV71)
We found that treatment with formononetin at 24 and 12 h before, and 0 to 6 h after EV71 infection was able to effectively reduce virusinduced cytopathic effect (CPE), while it did not exert this effect at −1, 9, (C)
Summary
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. We want to know whether a compound can inhibit EV71 infection by suppressing COX-2/PGE2 expression. EV71 is a common enterovirus that usually causes hand, foot and mouth disease in children mostly under 5 years. Most EV71 infections result in mild clinical symptoms and are self-limiting, small part EV71 infections is often associated with neurological diseases include aseptic meningitis, brain stem encephalitis and acute flaccid paralysis. EV71 was first isolated from patients with central nervous system diseases in California in 1969. Outbreaks have been periodically reported worldwide, especially in the. Hundreds of cases involving lethal complications have been reported in each outbreak [2,3]
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