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Background: Wogonin, a natural flavonoid-like chemical compound, exhibits anti-inflammatory, antitumor, antiviral, neuroprotective, and anxiolytic effects by modulating a variety of cellular signaling pathways including PI3K-Akt, p53, nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) pathways. In this study, its antiviral effect against herpes simplex virus (HSV) type 1 and 2 (HSV-1 and HSV-2) replication was investigated. Results: Wogonin suppressed HSV-2-induced cytopathic effect (CPE) and reduced viral mRNA transcription, viral protein synthesis, and infectious virion particle titers in a dose-dependent manner. A time-of-drug-addition assay demonstrated that wogonin acted as a postentry viral inhibitor. Wogonin also significantly reduced HSV-induced NF-κB and MAPK pathway activation, which has previously been demonstrated to be important for viral replication. Conclusions: Our results suggest that the anti-herpes effect of wogonin may be mediated by modulation of cellular NF-κB and JNK/p38 MAPK pathways and imply that wogonin may be useful as an anti-HSV agent. [ABSTRACT FROM AUTHOR]

Herpes simplex virus types 1 and 2 (HSV-1 and -2) are highly prevalent in many populations and therapeutic options are limited. Both viruses can establish latency by maintaining viral genomes in neurons of sensory ganglia. Primary or recurrent HSV infections may lead to deleterious outcomes: HSV-1 infection may result in corneal blindness and encephalitis and HSV-2 infection leads to herpes genitalis. While no effective vaccine is available, acyclovir is widely used for therapy, which targets and inhibits viral DNA polymerase. Although acyclovir is of low toxicity, resistant strains arise due to persistent use, mainly in immune compromised patients. In our effort to identify new HSV inhibitory molecules, harmine was found to potently inhibit HSV infection. Harmine, a beta-carbon alkaloid with an indole core structure and a pyridine ring, is widely distributed in plants. Earlier studies showed that harmine exhibited pharmacological activities such as antifungal, antimicrobial, antitumor, antiplasmodial and antioxidants. In the current study, we showed that harmine was a potent inhibitor of HSV-2 infection in vitro assays with EC 50 value at around 1.47 μM and CC 50 value at around 337.10 μM. The HSV RNA transcription, protein synthesis, and virus titers were reduced by the presence of harmine in a dose dependent manner. Further study on the mechanism of the anti-HSV activity showed that harmine blocked HSV-induced ROS production and the upregulated cytokine/chemokine expression, but our evidence showed that the inhibition of viral replication was unlikely mediated by the blocking of ROS production. We demonstrated that harmine significantly reduced HSV-2-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. We found that harmine also inhibited HSV-2-mediated p38 kinase and c-Jun N-terminal kinases (JNK) phosphorylation. [ABSTRACT FROM AUTHOR]