Details

Autor(en) / Beteiligte

• Lv, Xiao-fen
• Chen, Si-han
• Li, Jie
• Fang, Jian-ping
• Guo, Yue-wei
• Ding, Kan

Titel

Lobolide, a diterpene, blockades the NF-κB pathway and p38 and ERK MAPK activity in macrophages in vitro

Ist Teil von

• Acta pharmacologica Sinica, 2012-10, Vol.33 (10), p.1293-1300

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Aim： Recent studies have shown that constitutive activation of the nuclear factor κB （NF-κB） plays a key role in chronic inflammation and cancers. The aim of this study was to characterize lobolide, a cembrane diterpene, as a drug candidate targeting the NF-κB signaling pathway. Methods： A HEK 293/NF-κB-luc stable cell line was constructed to evaluate the effect of lobolide on NF-κB activation. THP-1 human monocytes and peripheral blood mononuclear cells （PBMCs） from healthy volunteers were tested. Lipopolysaccharide （LPS）-induced TNFα and IL-1β production and activation of the TAK1-IKK-NF-κB pathway were studied using ELISA and Western blot analysis.Results： In HEK 293/NF-κB-luc stable cells, lobolide （0.19–50 μmol/L） inhibited NF-κB activation in a concentration-dependent manner with an IC50 value of 4.2±0.3 μmol/L. Treatment with lobolide （2.5–10 μmol/L） significantly suppressed LPS-induced production of TNFα and IL-1β in both THP-1 cells and PBMCs. In THP-1 cells, the suppression was partially caused by blockade of the translocation of NF-κB from the cytoplasm to the nucleus via affecting the TAK1-IKK-NF-κB pathway and p38 and ERK MAPK activity.Conclusion： Lobolide is a potential inhibitor of the NF-κB pathway, which blocks the translocation of NF-κB from the cytoplasm to the nucleus. Lobolide inhibits LPS-stimulated TNFα and IL-1β release, suggesting that the compound might be an anti-inflammatory compound.