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

Zeng,Xiao-Yan; Yuan,Wei; Zhou,Lin; Wang,Shi-Xiu; Xie,Yong; Fu,Ying-Jun

doi:10.3892/ijmm.2017.2990

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

Authors:
- Xiao-Yan Zeng
- Wei Yuan
- Lin Zhou
- Shi-Xiu Wang
- Yong Xie
- Ying-Jun Fu
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Affiliations: Department of Pharmaceutical Sciences, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Pharmacy, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China, Department of Pharmacy, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330003, P.R. China, Department of Pharmacy, The 260th Hospital of Chinese People's Liberation Army, Shijiazhuang, Hebei 050041, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: May 15, 2017 https://doi.org/10.3892/ijmm.2017.2990
Pages: 243-250

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Abstract

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-κB signaling pathway, downregulating Foxp3, IL-10 and TGF-β1, 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.

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