Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rg5, a potent agonist of Nrf2, inhibits HSV-1 infection-induced neuroinflammation by inhibiting oxidative stress and NF-κB activation

  • Buyun Kim (Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM)) ;
  • Young Soo Kim (Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM)) ;
  • Wei Li (Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM)) ;
  • Eun-Bin Kwon (Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM)) ;
  • Hwan-Suck Chung (Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM)) ;
  • Younghoon Go (Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM)) ;
  • Jang-Gi Choi (Korean Medicine Application Center, Korea Institute of Oriental Medicine (KIOM))
  • Received : 2023.10.24
  • Accepted : 2024.01.22
  • Published : 2024.07.01
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Abstract

Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer's. The virus generates reactive oxygen species (ROS) that significantly impact viral replication 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 in the early stages of infection. Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 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-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.

Keywords

Acknowledgement

This research was conducted with financial support from the National Research Foundation of Korea (NRF) under grants NRF-RS-2023-00212563 and NRF-2021R1A2C2094436. And this work was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI23C1368).

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