The anti-malarial artemisinin inhibits pro-inflammatory cytokines via the NF-κB canonical signaling pathway in PMA-induced THP-1 monocytes.
ABSTRACT Several kinds of sesquiterpene lactones have been proven to inhibit NF-κB 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 (TNF)-α, interleukin (IL)-1ß, 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 NF-κB specific inhibitor, Bay 11-7082, inhibited the expression of these pro-inflammatory cytokines, suggesting that the NF-κB pathway may be involved in the decreased cytokine release. At all time-points (1-6 h), artemisinin impeded the phosphorylation of IKKα/ß, the phosphorylation and degradation of IκBα and the nuclear translocation of the NF-κB p65 subunit. Additionally, artemisinin inhibited the translocation of the NF-κB p65 subunit as demonstrated by confocal laser scanning microscopic analysis and by NF-κB 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.
- SourceAvailable from: Chih-Chun WenAdvances in Botanical Research, Edited by Lie-Fen Shyur and Allan S.Y. Lau, 01/2012: pages 197-272; Academic Press.
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ABSTRACT: BACKGROUND: The activation of nuclear factor-kappa B (NF-κB) and NLRP3 inflammasome is involved in neuroinflammation, which is closely linked to Alzheimer's disease (AD). In vivo and in vitro studies have suggested that artemisinin shows antiinflammatory effects in inflammation-related diseases. However, the impacts of artemisinin on AD have not been investigated. AIMS: In this study, 5-month-old APPswe/PS1dE9 transgenic mice were treated daily with 40 mg/kg artemisinin for 30 days by intraperitoneal injection to evaluate the effects of artemisinin on AD. RESULTS: We found that artemisinin treatment (1) decreased neuritic plaque burden; (2) did not alter Aβ transport across the blood-brain barrier; (3) regulated APP processing via inhibiting β-secretase activity; (4) inhibited NF-κB activity and NALP3 inflammasome activation in APPswe/PS1dE9 double transgenic mice. CONCLUSIONS: The in vivo study clearly demonstrates that artemisinin has protective effects on AD pathology due to its effects on suppressing NF-κB activity and NALP3 inflammasome activation. Our study suggests that targeting NF-κB activity and NALP3 inflammasome activation offers a valuable intervention for AD.CNS Neuroscience & Therapeutics 02/2013; · 4.46 Impact Factor
Article: Plant derived inhibitors of NF-κB[Show abstract] [Hide abstract]
ABSTRACT: Plant secondary metabolites (natural products) have been a source for many of our medicines. Their functions in plants remain often unknown, but in recent years there are more and more new compounds isolated and identified and their medicinal potential investigated. The major classes of plant natural products and various derivatives thereof are: phenolics, terpenoids, alkaloids and lignans. The major transcription factor, nuclear factor-κB (NF-κB) is a central downstream regulator of inflammation, cell proliferation and apoptosis that controls the expression of more than 500 genes. It plays an essential role in several aspects of human health including the development of innate and adaptive immunity. The deregulation of NF-κB is associated with many ailments including cancer and chronic inflammatory diseases. In spite of a vast literature describing NF-κB inhibitors from many natural or synthetic sources, such modulators have not been fully tapped for therapeutic purposes and the search for effective and specific inhibitors for therapeutic use and minimal side effects is still relevant and ongoing. Plant-derived phytochemicals are promising lead compounds to develop potent and safe inhibitors for cancer and inflammatory disorders driven by NF-κB. We briefly review the recent knowledge on plant derived phytochemicals and their major NF-κB molecular targets.Phytochemistry Reviews 01/2014; · 2.89 Impact Factor