Genistein antagonizes inflammatory damage induced by β-amyloid peptide in microglia through TLR4 and NF-κB.

OBJECTIVES

Microglia activation and neuroinflammation have been associated with the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB-mediated signal pathways exert key modulating roles in the inflammatory processes. The aim of the present study was to investigate whether genistein (Gen) has a neuroprotective effect against inflammatory damage induced by β-amyloid peptide25-35 (Aβ25-35) through the TLR4 and NF-κB-mediated signal pathways.

METHODS

BV-2 microglia cells were preincubated with Gen for 2 h and then treated with 25 μM Aβ25-35 for another 24 h. The expression of inflammatory mediators, TLR4 and NF-κB and the activity of NF-κB were measured.

RESULTS

The results showed that Gen could attenuate the cytotoxicity and inflammatory damage induced by Aβ25-35. Gen also significantly reversed Aβ25-35-induced up-regulation of TLR4 and NF-κB expression and the DNA binding and transcriptional activities of NF-κB.

CONCLUSION

These results indicated that Gen could alleviate the inflammation caused by Aβ25-35 treatment, which might be associated with the regulation of the TLR4/NF-κB signal pathway.