Dual effects of Korean red ginseng extract and its fractions on influenza A virus infectivity in lung-derived cell lines

Abstract

Background: Influenza infections are significantly affected by the genetics of the viruses and the cells they infect. Our previous studies showed that various influenza A subtypes uniquely infect different cell lines, offering insights into viral infection mechanisms. Meanwhile, Korean red ginseng extract (RGE) is known for its anti-influenza properties, attributed to its rich composition of saponin and non-saponin components. Purpose: This study evaluates the antiviral effects of RGE and its non-saponin (GNSF) and saponin (GSF) fractions against H1N1 and H9N2 influenza A subtypes in diverse cell lines. Study Design: Using various cell types and specialized assays, we explored the effect of pretreatment and continuous treatment with RGE and its fractions on viral infectivity and subsequent cellular responses. Methods: We treated several cell lines with varying concentrations of RGE, GNSF, and GSF and measured the cytotoxic effect, viral infectivity, oxidative stress levels, immune responses, autophagy activity, and changes in cellular structure. Results: Our findings demonstrate that RGE and its fractions significantly reduced H9N2 infection levels across multiple cell lines under pretreatment and continuous treatment conditions. However, continuous treatment elicited variable responses to H1N1, with increased infection levels in certain cell lines. Additionally, it elevated the production of reactive oxygen species and altered inflammatory responses, especially in A549 and NCI-H292 cells. GSF also modulated autophagy activity and MUC1 expression in response to H1N1. Conclusion: These findings highlight the potential of ginseng components as targeted influenza treatment, with cell line-specific responses that could guide treatment approaches.