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- W2029602672 abstract "Background and aim: High mobility group box 1 (HMGB1) protein is a highly conserved nuclear protein with important functions in the regulation of transcription. In inflammatory conditions, HMGB1 is actively secreted from immune cells in the extracellular matrix, where it behaviors as a pro-inflammatory cytokine. Dipotassium glycyrrhizate (DPG) is a glycyrrhizin-derived compound that is known to inhibit the pro-inflammatory activity of extracellular HMGB1. We previously showed that DPG significantly reduces, without adverse side effects, the DSS induced colitis in mice. Since a known relationship exists between HMGB1 and oxidative stress as well as between the latter and inflammation, the aim of the present study is to investigate whether DPG acts on the oxidative stress mechanisms to reduce inflammation Methods: In vivo: DPG (8mg/Kg) was administered to DSS-treated C57BL/6 mice. After 7 days, mice were sacrificed and inflamed colon removed. Expression levels of iNOS and COX2, involved in oxidative stress, were analysed by RT-PCR. In vitro: RAW267.4 cells were treated with LPS, DPG, LPS+DPG, HMGB1-B-Box, HMGB1-BBox+DPG at a earlier (4-8h) or later (24-48h) time. Expression levels of iNOS and COX2 were analysed by RT-PCR and AMPK phosphorylation was analysed by western blot. Results: In vivo: mice treated with DPG+DSS showed a significant decrease of iNOS and COX2 mRNA expression, compared to DSS-treated mice. In vitro: DPG reduced iNOS and COX2 expression induced by LPS at the later time and COX2 expression at the earlier time. Besides, HMGB1-B-Box increased iNOS expression at the earlier time, but this effect was counteracted by DPG. Finally, DPG induced AMPK phosphorylation, that is known to inhibit COX2, after LPS treatment. Conclusion: Our data show that DPG affects oxidative stress reducing iNOS and COX2 expression during inflammation. It is likely that DPG reduces iNOS through a mechanism HMGB1-dependent and COX2 through a mechanism AMK phosphorylation-mediated." @default.
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- W2029602672 date "2015-04-01" @default.
- W2029602672 modified "2023-09-25" @default.
- W2029602672 title "Tu1833 Dipotassium Glycyrrhizate Affects Oxidative Stress to Reduce Inflammation" @default.
- W2029602672 doi "https://doi.org/10.1016/s0016-5085(15)33103-6" @default.
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