Sanggenon C and O inhibit NO production, iNOS expression and NF-κB activation in LPS-induced RAW264.7 cells

Sanggenon C and O inhibit NO production, iNOS expression and NF-κB activation in LPS-induced RAW264.7 cells
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DOI:
10.3109/08923973.2011.580755
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发表时间:
2012-02-01
影响因子:
3.3
通讯作者:
Chau Van Minh
Chau Van Minh
中科院分区:
医学4区
文献类型:
--
作者:
Nguyen Tien Dat;Phung Thi Xuan Binh;Chau Van Minh

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目的:已知通过核因子(NF-κ B)的活化诱导iNOS产生的NO参与各种炎症状况。方法:采用SEAP报告基因分析法,观察桑根酮C和O对LPS刺激的RAW264.7细胞NO生成、iNOS表达和NF-κ B活性的影响。结果:两种化合物均呈剂量依赖性地抑制NO的生成和NF-κ B的活化。通过化合物(10和1 μ M)的处理也抑制了iNOS蛋白的表达。桑根酮O的抑制作用强于非对映体桑根酮C。这两种化合物阻止I κ B α蛋白的磷酸化和降解。结论:我们证明,sanggenon C和O通过抑制NF-κ B活性和I κ B α激活来抑制NO的产生和iNOS的表达。
Objective: The NO production through the iNOS induction by activation of nuclear factor (NF-kappa B) is known to involve in various inflammatory conditions. Sanggenon C and O, two Diels-Alder type adducts isolated from Morus alba, a plant has been used for the anti-inflammatory purpose in the Oriental medicine, were investigated for their effect on the NO production, iNOS expression and NF-kappa B activity.Methods: The inhibitory effects of sanggenon C and O on the NF-kappa B activity were investigated in LPS-stimulated RAW264.7 cells by SEAP reporter assay. The regulation of the iNOS expression and I kappa B alpha activation by two compounds was also evaluated by Western blot.Results: Both compounds strongly inhibited NO production and NF-kappa B activation in a dose-dependent manner. The expression of the iNOS protein was also suppressed by treatment of the compounds (10 and 1 mu M). Sanggenon O showed stronger inhibition than the diastereomer sanggenon C. Both compounds prevented the phosphorylation and degradation of I kappa B alpha protein.Conclusion: We demonstrated that sanggenon C and O inhibited NO production and iNOS expression by suppressing NF-kappa B activity and I kappa B alpha activation.