Soyasaponins Can Blunt Inflammation by Inhibiting the Reactive Oxygen Species-Mediated Activation of PI3K-Akt-NF-kB PathwayReport as inadecuate




Soyasaponins Can Blunt Inflammation by Inhibiting the Reactive Oxygen Species-Mediated Activation of PI3K-Akt-NF-kB Pathway - Download this document for free, or read online. Document in PDF available to download.

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 A1, A2 and I inhibited the lipopolysaccharide LPS-induced release of inflammatory marker prostaglandin E2 PGE2 to a similar extent as the NF-kB inhibitor BAY117082. Soyasaponins A1, A2 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 A1, A2 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 A1, A2 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 A1, A2 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, PGE2 production, and malondialdehyde production. Finally, our results show that soyasaponins A1, A2 and I elevated SOD activity and the GSH-GSSG ratio. Together, these results show that soyasaponins A1, A2 and I can blunt inflammation by inhibiting the ROS-mediated activation of the PI3K-Akt-NF-kB pathway.



Author: Longying Zha , Jiading Chen, Suxia Sun, Limei Mao, Xinwei Chu, Hong Deng, Junwei Cai, Xuefeng Li, Zhenqi Liu, Wenhong Cao

Source: http://plos.srce.hr/



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