Ginsenosides Rb1 and Rg1 Suppress Lipopolysaccharide-Induced Inflammatory Gene Expression in Microglia and...

Neuroinflammation, mediated by activated microglia and astrocytes, contributes to the progression of neurodegenerative diseases. Ginsenosides derived from Panax ginseng possess anti-inflammatory properties. However, the comparative efficacy of structurally distinct ginsenosides and their activity across multiple glial cell types remains incompletely understood. In this study, we systematically compared the effects of ginsenosides Rb1 (protopanaxadiol-type), Rb2 (protopanaxadiol-type), and Rg1 (protopanaxatriol-type) in lipopolysaccharide (LPS)-activated BV2 microglia and C8-D1A astrocytes. Following LPS stimulation, cells were treated with ginsenosides, and inflammatory responses were assessed by cell viability assay, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and western blotting. None of the three ginsenosides up to 20 μM concentration reduced cell viability. Rb1 and Rg1 suppressed LPS-induced expression of proinflammatory genes, including Il-6, Il-1β, and Cox-2, across multiple concentrations, with inhibitory effects particularly notable at 5 and 10 μM. ELISA further confirmed that Rb1 and Rg1 reduced interleukin (IL)-6 and IL-1β secretion in both glial cell types. In contrast, Rb2 showed limited and inconsistent anti-inflammatory effects, despite being structurally similar to Rb1. Rb1 and Rg1 reduced LPS-induced phosphorylation of nuclear factor kappa B (NF-κB) in nuclei of both cell types, whereas Rb2 suppressed NF-κB phosphorylation only in BV2 microglia. Rb1 reduced AKT and p38 phosphorylation in C8-D1A astrocytes, indicating compound- and cell-type-specific regulation of inflammatory signaling. Notably, Rb2-mediated NF-κB suppression did not translate into broad inhibition of inflammatory gene or cytokine expression. These findings identify Rb1 and Rg1 as ginsenosides with broad anti-inflammatory activity in microglia and highlight glycosylation-dependent functional differences among structurally related ginsenosides.