Open AccessSoyasaponins Can Blunt Inflammation by Inhibiting the Reactive Oxygen Species-Mediated Activation of PI3K/Akt/NF-kB Pathway
Author(s) -
Longying Zha,
Jiading Chen,
Song Sun,
Limei Mao,
Xinwei Chu,
Hong Deng,
Jianwei Cai,
Xuefeng Liu,
Zhenqi Liu,
Wenhong Cao
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0107655
Subject(s) - protein kinase b , phosphorylation , pi3k/akt/mtor pathway , chemistry , ly294002 , nf κb , reactive oxygen species , inflammation , nfkb1 , iκbα , iκb kinase , microbiology and biotechnology , signal transduction , biochemistry , biology , transcription factor , immunology , gene
We and others have recently shown that soyasaponins abundant in soybeans can decrease inflammation by suppressing the nuclear factor kappa B (NF-kB)-mediated inflammation. However, the exact molecular mechanisms by which soyasaponins inhibit the NF-kB pathway have not been established. In this study in macrophages, soyasaponins (A 1 , A 2 and I) inhibited the lipopolysaccharide (LPS)-induced release of inflammatory marker prostaglandin E 2 (PGE 2 ) to a similar extent as the NF-kB inhibitor (BAY117082). Soyasaponins (A 1 , A 2 and I) also suppressed the LPS-induced expression of cyclooxygenase 2 (COX-2), another inflammatory marker, in a dose-dependent manner by inhibiting NF-kB activation. In defining the associated mechanisms, we found that soyasaponins (A 1 , A 2 and I) blunted the LPS-induced IKKα/β phosphorylation, IkB phosphorylation and degradation, and NF-kB p65 phosphorylation and nuclear translocation. In studying the upstream targets of soyasaponins on the NF-kB pathway, we found that soyasaponins (A 1 , A 2 and I) suppressed the LPS-induced activation of PI3K/Akt similarly as the PI3K inhibitor LY294002, which alone blocked the LPS-induced activation of NF-kB. Additionally, soyasaponins (A 1 , A 2 and I) reduced the LPS-induced production of reactive oxygen species (ROS) to the same extent as the anti-oxidant N-acetyl-L-cysteine, which alone inhibited the LPS-induced phosphorylation of Akt, IKKα/β, IkBα, and p65, transactivity of NF-kB, PGE 2 production, and malondialdehyde production. Finally, our results show that soyasaponins (A 1 , A 2 and I) elevated SOD activity and the GSH/GSSG ratio. Together, these results show that soyasaponins (A 1 , A 2 and I) can blunt inflammation by inhibiting the ROS-mediated activation of the PI3K/Akt/NF-kB pathway.