Ginsenoside Rg5, a potent agonist of Nrf2, inhibits HSV-1 infection-induced neuroinfl ammation by inhibiting oxidative stress and NF-κB activation

다국어 초록 (Multilingual Abstract)

Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host’s trigeminal ganglion, canlead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerativediseases like Alzheimer’s. The virus generates reactive oxygen species (ROS) that significantly impact viralreplication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2),an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response inthe early stages of infection.
Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity inhost cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenosideRg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction.
Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1)and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition,a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication.
Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.