Stevioside Suppressed Inflammatory Cytokine Secretion by Downregulation of NF-κB and MAPK Signaling Pathways in LPS-Stimulated RAW264.7 Cells

Stevioside, a diterpene glycoside isolated from Stevia rebaudiana, has been reported to have anti-inflammatory properties. However, the underlying molecular mechanisms are not well understood. The objective of this study was to investigate the molecular mechanism of stevioside in modifying lipopolysaccharide (LPS)-induced signal pathways in RAW264.7 cells. RAW264.7 cells were stimulated with LPS in the presence or absence of stevioside. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. Nuclear factor-kappa B (NF-kappa B), inhibitory kappa B (I kappa B alpha) protein, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) were determined by western blot. The results showed that stevioside dose-dependently inhibited the expression of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta in LPS-stimulated RAW264.7 cells. Western blot analysis showed that stevioside suppressed LPS-induced NF-kappa B activation, I kappa Ba degradation, phosphorylation of ERK, JNK, and P38. Our results suggest that stevioside exerts an anti-inflammatory property by inhibiting the activation of NF-kappa B and mitogen-activated protein kinase signaling and the release of proinflammatory cytokines. These findings suggest that stevioside may be a therapeutic agent against inflammatory diseases.