Journal Articles

Soyasaponins Can Blunt Inflammation by Inhibiting the Reactive Oxygen Species-Mediated Activation of PI3K/Akt/NF-kB Pathway.

September 01, 2014

Soyasaponins Can Blunt Inflammation by Inhibiting the Reactive Oxygen Species-Mediated Activation of PI3K/Akt/NF-kB Pathway. PLoS One. 2014 Sep 1, Zha L1, Chen J2, Sun S2, Mao L2, Chu X2, Deng H2, Cai J3, Li X4, Liu Z5, Cao W6.

  • 1Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China; Nutrition Research Institute at Kannapolis, Department of Nutrition, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • 2Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
  • 3Department of Endocrinology, Taihe Hospital, Hubei University of Medicine, Shiyan, China; Nutrition Research Institute at Kannapolis, Department of Nutrition, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
  • 4Department of Endocrinology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
  • 5Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, United States of America.
  • 6Department of Endocrinology, Taihe Hospital, Hubei University of Medicine, Shiyan, China; Nutrition Research Institute at Kannapolis, Department of Nutrition, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Medicine (Endocrinology and Metabolism), Duke University School of Medicine, Durham, North Carolina, United States of America.

Abstract

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 oxygenspecies (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 inhibitingthe ROS-mediated activation of the PI3K/Akt/NF-kB pathway.

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