Rosmarinic acid-mediated downregulation of RIG-I and p62 in microglia confers resistance to Japanese encephalitis virus-induced inflammation.

Abstract

Background: Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic pathogen that causes encephalitis in humans and reproductive failure in pigs. The transmission of JEV between humans and animals poses a significant public health threat and results in substantial economic losses. Excessive inflammation in the central nervous system of JEV-infected patients is a major cause of mortality and disability. Rosmarinic acid (RA), a polyhydroxyphenolic compound isolated from medicinal herbs, has been preliminarily shown to possess anti-inflammatory properties and significantly inhibit JEV-induced neuroinflammation in mice.

Results: This study investigated the antiviral capacity and potential mechanisms of RA in JEV-infected cells. The results demonstrated that RA could inhibit JEV replication in vitro. Furthermore, the expression levels of inflammatory cytokines (including IL-6, IL-1β, CCL-2, and TNF-α), membrane receptors (including RIG-I, TLR3, TLR4, TLR7, and TLR8), NF-κB complex and p62/SQSTM1 were assessed using qPCR, ELISA, and Western blot, respectively. The findings indicated that RA significantly suppressed the expression of IL-6, IL-1α, TNF-α, and CCL-2 in JEV-infected BV-2 cells in a dose-dependent manner. Additionally, RA treatment downregulated the expression levels of RIG-I and p62, while p62 silencing inhibited the upregulation of inflammatory cytokines in JEV-infected BV-2 cells.

Conclusion: Our present study highlights the important role of RA-mediated reduction of RIG-I and p62 in microglia, conferring resistance to Japanese encephalitis virus-induced inflammation.