PMID- 36077522 OWN - NLM STAT- MEDLINE DCOM- 20220912 LR - 20220913 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 17 DP - 2022 Sep 4 TI - Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-kappaB/NLRP3/GSDMD Signaling Cascades. LID - 10.3390/ijms231710124 [doi] LID - 10124 AB - 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 mug/mL LPS to induce cell pyroptosis and were treated with 10, 50, or 100 mug/mL MF for regulating pyroptosis. The cell supernatants TNF-alpha, IL-1beta, IL-6, and IL-18 were detected by enzyme-linked immunosorbent assay (ELISA); gene expression of TNF-alpha, IL-1beta, IL-6, IL-18, Caspase-1, Caspase-11, and gasdermin D (GSDMD) 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-kappaB were detected by Western blot. The results showed that MF significantly inhibited the secretion and gene expression of TNF-alpha, IL-6, IL-1beta, and IL-18 that were elevated by LPS. Moreover, MF significantly suppressed the gene expression of Caspase-1, Caspase-11, and GSDMD, and decreased the protein levels of NLRP3, caspase-1, caspase-11, full-length GSDMD (GSDMD-FL), GSDMD N-terminal (GSDMD-N), and NF-kappaB. In conclusion, mangiferin has a multi-target regulating effect on inflammation and pyroptosis by inhibiting the NF-kappaB pathway, suppressing inflammatory caspase-mediated pyroptosis cascades, and reducing GSDMD cleavage in LPS-induced BMDMs. FAU - Feng, Min AU - Feng M AD - College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China. AD - Engineering 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, China. FAU - Wei, Shaoqiang AU - Wei S AD - Engineering 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, China. FAU - Zhang, Shidong AU - Zhang S AUID- ORCID: 0000-0002-3045-9010 AD - Engineering 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, China. FAU - Yang, Ying AU - Yang Y AD - College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China. LA - eng PT - Journal Article DEP - 20220904 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Inflammasomes) RN - 0 (Interleukin-18) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLR Proteins) RN - 0 (Nlrp3 protein, mouse) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Xanthones) RN - 1M84LD0UMD (mangiferin) RN - EC 3.4.22.- (Caspases) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Caspase 1/metabolism MH - Caspases MH - Inflammasomes/metabolism MH - Interleukin-18 MH - Interleukin-6 MH - Lipopolysaccharides/pharmacology MH - Mice MH - NF-kappa B/metabolism MH - *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - NLR Proteins MH - Tumor Necrosis Factor-alpha MH - *Xanthones/pharmacology PMC - PMC9456045 OTO - NOTNLM OT - GSDMD OT - LPS OT - inflammatory caspases OT - mangiferin OT - pyroptosis COIS- The authors declare no conflict of interest. EDAT- 2022/09/10 06:00 MHDA- 2022/09/14 06:00 PMCR- 2022/09/04 CRDT- 2022/09/09 01:09 PHST- 2022/08/15 00:00 [received] PHST- 2022/08/30 00:00 [revised] PHST- 2022/09/01 00:00 [accepted] PHST- 2022/09/09 01:09 [entrez] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/09/04 00:00 [pmc-release] AID - ijms231710124 [pii] AID - ijms-23-10124 [pii] AID - 10.3390/ijms231710124 [doi] PST - epublish SO - Int J Mol Sci. 2022 Sep 4;23(17):10124. doi: 10.3390/ijms231710124.