Artemisinin inhibits inflammatory response via regulating NF-κB and MAPK signaling pathways

Immunopharmacol Immunotoxicol. 2017 Feb;39(1):28-36. doi: 10.1080/08923973.2016.1267744. Epub 2016 Dec 21.

Abstract

Artemisinin, isolated from the Chinese plant Artemisia annua, has been used for many years to treat different forms of malarial parasites. In this study, we explored the anti-inflammatory activity of artemisinin and the underlying mechanism of this action. We demonstrated that the anti-inflammatory effects of artemisinin in TPA-induced skin inflammation in mice. Then the artemisinin significantly inhibited the expression of NF-κB reporter gene induced by TNF-α in a dose-dependent manner. Artemisinin also inhibited TNF-α induced phosphorylation and degradation of IκBα, p65 nuclear translocation. Artemisinin also has an impact on upstream signaling of IKK through the inhibition of expression of adaptor proteins, TNF receptor-associated factor 2 (TRAF2) and receptor interacting protein 1 (RIP1). Furthermore, pretreatment of cells with artemisinin prevented the TNF-α-induced expression of NF-κB target genes, such as anti-apoptosis (c-IAP1, Bcl-2, and FLIP), proliferation (COX-2, cyclinD1), invasion (MMP-9), angiogenesis (VEGF), and major inflammatory cytokines (TNF-α, iNOS, and MCP1). We also proved that artemisinin potentiated TNF-α-induced apoptosis. Moreover, artemisinin significantly impaired the ROS production and phosphorylation of p38 and ERK, but did not affect the phosphorylation of JNK. Taken together, artemisinin may be a potentially useful therapeutic agent for inflammatory-related diseases.

Keywords: Artemisinin; Inflammation; IκBα; MAPK; Nuclear factor-κB (NF-κB).

MeSH terms

  • Animals
  • Artemisinins / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / immunology
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / immunology
  • Mice
  • NF-kappa B / immunology*
  • Nuclear Pore Complex Proteins / immunology
  • RNA-Binding Proteins / immunology
  • TNF Receptor-Associated Factor 1 / immunology
  • TNF Receptor-Associated Factor 2 / immunology
  • Tumor Necrosis Factor-alpha / adverse effects
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • AGFG1 protein, human
  • Artemisinins
  • NF-kappa B
  • Nuclear Pore Complex Proteins
  • RNA-Binding Proteins
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor-alpha
  • artemisinine