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-κB (NF-κB), inhibitory kappa B (IκBα) 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-α, interleukin-6, and interleukin-1β in LPS-stimulated RAW264.7 cells. Western blot analysis showed that stevioside suppressed LPS-induced NF-κB activation, IκBa degradation, phosphorylation of ERK, JNK, and P38. Our results suggest that stevioside exerts an anti-inflammatory property by inhibiting the activation of NF-κB 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.
College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
Li
L
Fengyang
Fu
F
Yunhe
Liu
L
Bo
Liu
L
Zhicheng
Li
L
Depeng
Liang
L
Dejie
Zhang
Z
Wen
Cao
C
Yongguo
Zhang
Z
Naisheng
Zhang
Z
Xichen
Yang
Y
Zhengtao
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D015536:Down-Regulation; D005960:Glucosides / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D045786:Diterpenes, Kaurane; D005960:Glucosides; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C012043:stevioside; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases