Forsythoside A exerts an anti-endotoxin effect by blocking the LPS/TLR4 signaling pathway and inhibiting Tregs in vitro

Endotoxins, also referred to as lipopolysaccharides (LPS), are powerful immunostimulators involved in a number of severe diseases. Forsythoside A (FTA), a monomer of phenethyl alcohol glycosides extracted from Forsythia suspensa, has been shown to possess anti-bacterial and immunomodulatory properties. However, it is currently not known whether FTA can counter the adverse effects of endotoxins. We investigated the effect of FTA on LPS-stimulated RAW264.7 cells and primary lymphocytes to determine its molecular mechanism of action. RAW264.7 cells and primary lymphocytes were incubated with or without LPS (100 ng/ml) in the presence or absence of FTA or polymyxin B. We found that FTA increased the viability of LPS-treated RAW264.7 cells and primary lymphocytes suggesting that FTA effectively counters the adverse effects of endotoxins. FTA decreased the percentage of regulatory T cells (Tregs) and inhibited the TLR4/MyD88/NF-B signaling pathway, downregulating Foxp3, IL-10 and TGF-1, molecules involved in the immunosuppressive function of Tregs. These findings elucidate the molecular mechanism underlying the anti-endotoxin effects of FTA and suggest its use as a new treatment for LPS-induced diseases.