Ginsenoside Rg1 Regulates NLRP3 Expression and Suppresses IL-1β Production

Neuroinflammation is a major contributor to the pathogenesis of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. A key mediator of this process is the NLRP3 inflammasome in microglia, which activates caspase-1 and drives the maturation and release of pro-inflammatory cytokines including IL-1β. Excessive or sustained activation of the NLRP3 inflammasome promotes neuronal dysfunction, highlighting it as a potential therapeutic target. Ginsenoside Rg1, a predominant bioactive compound of Panax ginseng C. A. Meyer, is known for its antioxidant and anti-inflammatory properties; however, its direct role in regulating NLRP3 remains poorly understood. In this study, we examined the effects of Rg₁ on NLRP3 expression and IL-1β production in BV2 microglial cells. MTT assay confirmed that Rg₁ up to 300 μg/mL had no cytotoxic effect. Western blot analysis demonstrated that Rg1 pretreatment significantly suppressed LPS-induced NLRP3 protein expression and reduced IL-1β levels, whereas qPCR analysis revealed no change in NLRP3 mRNA expression. These findings suggest that Rg1 regulates NLRP3 at the post-transcriptional level. Consistent with this, the DARTS assay indicated a direct binding interaction between Rg₁ and NLRP3. Taken together, these results identify ginsenoside Rg₁ as a promising candidate for the prevention or treatment of neuroinflammatory diseases.