title: Soyasaponins can blunt inflammation by inhibiting the reactive oxygen species-mediated activation of PI3K/Akt/NF-kB pathway.
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 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.
authors.affiliation: Department 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.
authors.forename: Longying
authors.initials: L
authors.lastname: Zha
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Jiading
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Chu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department 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.
authors.forename: Junwei
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Endocrinology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, United States of America.
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department 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.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Cao
mesh_terms: D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013025:Glycine max / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D002867:Chromones; D008070:Lipopolysaccharides; D009025:Morpholines; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species; C498144:Rela protein, mouse; D012503:Saponins; D013450:Sulfones; D051996:Transcription Factor RelA; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D008315:Malondialdehyde; C056684:soyasaponin I; D009828:Oleanolic Acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; D015232:Dinoprostone