Zha Longying, Chen Jiading, Sun Suxia, Mao Limei, Chu Xinwei, Deng Hong, Cai Junwei, Li Xuefeng, Liu Zhenqi, Cao Wenhong
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.
Department of Nutrition and Food Hygiene, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
PLoS One. 2014 Sep 18;9(9):e107655. doi: 10.1371/journal.pone.0107655. eCollection 2014.
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.
我们和其他研究人员最近发现，大豆中富含的大豆皂苷可通过抑制核因子κB（NF-κB）介导的炎症反应来减轻炎症。然而，大豆皂苷抑制NF-κB途径的确切分子机制尚未明确。在这项针对巨噬细胞的研究中，大豆皂苷（A1、A2和I）抑制脂多糖（LPS）诱导的炎症标志物前列腺素E2（PGE2）释放的程度与NF-κB抑制剂（BAY117082）相似。大豆皂苷（A1、A2和I）还通过抑制NF-κB激活，以剂量依赖的方式抑制LPS诱导的另一种炎症标志物环氧合酶2（COX-2）的表达。在确定相关机制时，我们发现大豆皂苷（A1、A2和I）可减弱LPS诱导的IKKα/β磷酸化、IkB磷酸化和降解以及NF-κB p65磷酸化和核转位。在研究大豆皂苷在NF-κB途径上的上游靶点时，我们发现大豆皂苷（A1、A2和I）抑制LPS诱导的PI3K/Akt激活的程度与PI3K抑制剂LY294002相似，而LY294002单独使用时可阻断LPS诱导的NF-κB激活。此外，大豆皂苷（A1、A2和I）将LPS诱导的活性氧（ROS）产生降低到与抗氧化剂N-乙酰-L-半胱氨酸相同的程度，N-乙酰-L-半胱氨酸单独使用时可抑制LPS诱导的Akt、IKKα/β、IkBα和p65磷酸化、NF-κB的转录活性、PGE2产生以及丙二醛产生。最后，我们的结果表明大豆皂苷（A1、A2和I）可提高超氧化物歧化酶（SOD）活性以及谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）比值。综上所述，这些结果表明大豆皂苷（A1、A2和I）可通过抑制ROS介导的PI3K/Akt/NF-κB途径激活来减轻炎症。
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