The anti-malarial artemisinin inhibits pro-inflammatory cytokines via the NF-κB canonical signaling pathway in PMA-induced THP-1 monocytes

Several kinds of sesquiterpene lactones have been proven to inhibit NE-kappa B and to retard atherosclerosis by reducing lesion size and changing plaque composition. The anti-malarial artemisinin (Art) is a pure sesquiterpene lactone extracted from the Chinese herb Artemisia annua (qinghao, sweet wormwood). In the present study, we demonstrate that artemisinin inhibits the secretion and the mRNA levels of tumor necrosis factor (TNE)-alpha, interleukin (IL)-1 beta, and IL-6 in a dose-dependent manner in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 human monocytes. We also found that the NE-kappa B specific inhibitor, Bay 11-7082, inhibited the expression of these pro-inflammatory cytokines, suggesting that the NF-kappa B pathway may be involved in the decreased cytokine release. At all time-points (1-6 h), artemisinin impeded the phosphorylation of IKK alpha/beta, the phosphorylation and degradation of I kappa B alpha and the nuclear translocation of the NF-kappa B p65 subunit. Additionally, artemisinin inhibited the translocation of the NE-kappa B p65 subunit as demonstrated by confocal laser scanning microscopic analysis and by NE-kappa B binding assays. Our data indicate that artemisinin exerts an anti-inflammatory effect on PMA-induced THP-1 monocytes, suggesting the potential role of artemisinin in preventing the inflammatory progression of atherosclerosis.