Daidzein attenuates lipopolysaccharide-induced acute lung injury via toll-like receptor 4/NF-kappaB pathway

• Daidzein offers a protective role against LPS-induced ALI. Daidzein may be a potential therapeutic reagent for ALI.
• The anti-inflammatory effects of daidzein may be due to its ability to inhibit toll-like receptor 4 pathway.
• The protection of daidzein against LPS-induced ALI may involve the inhibition of TLR4-MyD88-NF-κB signaling pathway.

Daidzein, a diphenolic isoflavone from many plants and herbs, has been reported to have anti-inflammatory properties. However, the effects of daidzein on lipopolysaccharide (LPS)-induced acute lung injury have not been determined. The aim of this study was to detect the effects of daidzein on LPS-induced acute lung injury and investigate the molecular mechanisms. Daidzein was intraperitoneally injected (2, 4, 8 mg/kg) 30 min after intratracheal instillation of LPS (5 mg/kg) in rats. The results showed that daidzein treatment remarkably improved the pulmonary histology and decreased the lung wet/dry weight ratios. We also found that daidzein significantly inhibited LPS-induced increases of macrophages and neutrophils infiltration of lung tissues, as well as markedly attenuated MPO activity. Moreover, daidzein effectively reduced the inflammatory cytokines release and total protein in bronchoalveolar lavage fluids (BALF). Furthermore, daidzein significantly inhibited LPS-induced toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) protein up-expressions and NF-κB activation in lung tissues. In vitro, daidzein obviously inhibited the expressions of TLR4 and MyD88 and the activation of NF-κB in LPS-stimulated A549 alveolar epithelial cells. In conclusion, these data indicate that the anti-inflammatory effects of daidzein against LPS-induced ALI may be due to its ability to inhibit TLR4-MyD88-NF-κB pathway and daidzein may be a potential therapeutic agent for LPS-induced ALI.