Abstract
Microglial activation plays an important role in neuroinflammation, which contributes to neuronal damage, and inhibition of microglial activation may have therapeutic benefits that could alleviate the progression of neurodegeneration. Recent studies have indicated that the antimalarial agent artemisinin has the ability to inhibit NF-κB activation. In this study, the inhibitory effects of artemisinin on the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated primary microglia. Our results show that artemisinin significantly inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO). Artemisinin significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) and increased the protein levels of IκB-α, which forms a cytoplasmic inactive complex with the p65-p50 heterodimeric complex. Artemisinin treatment significantly inhibited basal and LPS-induced migration of BV-2 microglia. Electrophoretic mobility shift assays revealed increased NF-κB binding activity in LPS-stimulated primary microglia, and this increase could be prevented by artemisinin. The inhibitory effects of artemisinin on LPS-stimulated microglia were blocked after IκB-α was silenced with IκB-α siRNA. Our results suggest that artemisinin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The data provide direct evidence of the potential application of artemisinin for the treatment of neuroinflammatory diseases.
Highlights
Microglia, which are the resident macrophages of the central nervous system (CNS), are recognized as the primary component of the brain immune system [1]
No significant differences in cell viability were found between normal primary rat microglia and microglia treated with 10 mM artemisinin for 48 h (Fig. 1), which indicates that the inhibitory effect that we observed was not due to cytotoxicity
Artemisinin inhibits nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production in LPSstimulated primary rat microglia To investigate the effects of artemisinin on NO production in LPS-stimulated primary rat microglia, cells were treated with LPS alone or with various concentrations of artemisinin for 24 h
Summary
Microglia, which are the resident macrophages of the central nervous system (CNS), are recognized as the primary component of the brain immune system [1]. They are activated during neuropathological conditions to restore CNS homeostasis [2]. Microglia undergo morphological changes, proliferate and upregulate surface molecules [3]. Studies have demonstrated that the inhibition of pro-inflammatory mediators in microglia can attenuate the severity of Alzheimer’s disease (AD), Parkinson’s disease (PD), trauma, multiple sclerosis (MS) and cerebral ischemia [5,6,7,8,9]. Anti-inflammatory treatment via inhibition of microglial activation is regarded as a promising strategy for the prevention of neurodegenerative diseases [10]
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