Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades
Mangiferin (MF), a xanthone that extensively exists in many herbal medicines, processes significant activities of anti-inflammation and immunomodulation. The potential regulatory effect and mechanism of mangiferin on cell pyroptosis remain unclear. In this study, mouse bone-marrow-derived macrophage...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/17/10124 |
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| author | Min Feng Shaoqiang Wei Shidong Zhang Ying Yang |
| author_facet | Min Feng Shaoqiang Wei Shidong Zhang Ying Yang |
| author_sort | Min Feng |
| collection | DOAJ |
| description | Mangiferin (MF), a xanthone that extensively exists in many herbal medicines, processes significant activities of anti-inflammation and immunomodulation. The potential regulatory effect and mechanism of mangiferin on cell pyroptosis remain unclear. In this study, mouse bone-marrow-derived macrophages (BMDMs) were stimulated with 1 μg/mL LPS to induce cell pyroptosis and were treated with 10, 50, or 100 μg/mL MF for regulating pyroptosis. The cell supernatants TNF-α, IL-1β, IL-6, and IL-18 were detected by enzyme-linked immunosorbent assay (ELISA); gene expression of <i>TNF-α</i>, <i>IL-1β</i>, <i>IL-6</i>, <i>IL-18</i>, <i>Caspase-1</i>, <i>Caspase-11</i>, and <i>gasdermin D</i> (<i>GSDMD</i>) was tested by real-time polymerase chain reaction (RT-PCR), and protein expression levels of apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), nod-like receptor protein-3 (NLRP3), caspase-1, caspase-11, GSDMD, and NF-κB were detected by Western blot. The results showed that MF significantly inhibited the secretion and gene expression of TNF-α, IL-6, IL-1β, and IL-18 that were elevated by LPS. Moreover, MF significantly suppressed the gene expression of <i>Caspase-1</i>, <i>Caspase-11</i>, and <i>GSDMD</i>, and decreased the protein levels of NLRP3, caspase-1, caspase-11, full-length GSDMD (GSDMD-FL), GSDMD N-terminal (GSDMD-N), and NF-κB. In conclusion, mangiferin has a multi-target regulating effect on inflammation and pyroptosis by inhibiting the NF-κB pathway, suppressing inflammatory caspase-mediated pyroptosis cascades, and reducing GSDMD cleavage in LPS-induced BMDMs. |
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| spelling | doaj.art-1262c245d3c44fc18df6c3849c2d57df2023-11-23T13:23:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123171012410.3390/ijms231710124Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling CascadesMin Feng0Shaoqiang Wei1Shidong Zhang2Ying Yang3College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, ChinaEngineering Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Animal Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, ChinaEngineering Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Animal Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, ChinaCollege of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, ChinaMangiferin (MF), a xanthone that extensively exists in many herbal medicines, processes significant activities of anti-inflammation and immunomodulation. The potential regulatory effect and mechanism of mangiferin on cell pyroptosis remain unclear. In this study, mouse bone-marrow-derived macrophages (BMDMs) were stimulated with 1 μg/mL LPS to induce cell pyroptosis and were treated with 10, 50, or 100 μg/mL MF for regulating pyroptosis. The cell supernatants TNF-α, IL-1β, IL-6, and IL-18 were detected by enzyme-linked immunosorbent assay (ELISA); gene expression of <i>TNF-α</i>, <i>IL-1β</i>, <i>IL-6</i>, <i>IL-18</i>, <i>Caspase-1</i>, <i>Caspase-11</i>, and <i>gasdermin D</i> (<i>GSDMD</i>) was tested by real-time polymerase chain reaction (RT-PCR), and protein expression levels of apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), nod-like receptor protein-3 (NLRP3), caspase-1, caspase-11, GSDMD, and NF-κB were detected by Western blot. The results showed that MF significantly inhibited the secretion and gene expression of TNF-α, IL-6, IL-1β, and IL-18 that were elevated by LPS. Moreover, MF significantly suppressed the gene expression of <i>Caspase-1</i>, <i>Caspase-11</i>, and <i>GSDMD</i>, and decreased the protein levels of NLRP3, caspase-1, caspase-11, full-length GSDMD (GSDMD-FL), GSDMD N-terminal (GSDMD-N), and NF-κB. In conclusion, mangiferin has a multi-target regulating effect on inflammation and pyroptosis by inhibiting the NF-κB pathway, suppressing inflammatory caspase-mediated pyroptosis cascades, and reducing GSDMD cleavage in LPS-induced BMDMs.https://www.mdpi.com/1422-0067/23/17/10124mangiferinLPSpyroptosisinflammatory caspasesGSDMD |
| spellingShingle | Min Feng Shaoqiang Wei Shidong Zhang Ying Yang Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades International Journal of Molecular Sciences mangiferin LPS pyroptosis inflammatory caspases GSDMD |
| title | Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades |
| title_full | Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades |
| title_fullStr | Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades |
| title_full_unstemmed | Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades |
| title_short | Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades |
| title_sort | anti inflammation and anti pyroptosis activities of mangiferin via suppressing nf κb nlrp3 gsdmd signaling cascades |
| topic | mangiferin LPS pyroptosis inflammatory caspases GSDMD |
| url | https://www.mdpi.com/1422-0067/23/17/10124 |
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