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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/17/10124 |
| Summary: | 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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| ISSN: | 1661-6596 1422-0067 |