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. 2018 Aug 24;8:12784. doi: 10.1038/s41598-018-31218-7

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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NATxME anti-inflammatory and cytoprotective effects. NATxME inhibits the secretion of pro-inflammatory cytokines (A–C). RAW 264.7 macrophages were treated with NATxME 1, 3 and 10 µM for 2 h and then stimulated with LPS (50 ng/ml) for 18 h. The secretion of inflammatory cytokines MCP-1 (A), IL-6 (B) and TNF-α (C) was analyzed by ELISA in the supernatant. Values are shown as mean ± SD. Statistical analysis: one-way ANOVA Bonferroni’s multiple comparison test. (A) * = 0.0294; ** = 0.0017; **** < 0.0001. (B) ** = 0.013; **** < 0.0001. (C) * = 0.0131. vs. LPS. NATxME induces the Nrf2-Keap-1 system (D–F). Raw 264.7 macrophages were treated with NATxME 1, 3 and 10 µM for 5 h. The expression of NQO1 (D), GCLM (E) and HO-1 (F) were analyzed by quantitative RT-PCR. Values are shown as mean ± SD. Statistical analysis: one-way ANOVA Bonferroni’s multiple comparison test. (D) ** = 0.0038. (E) * = 0.0310; *** = 0.0001. (F) *** = 0.0001. vs control.