Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades

Area of Science:

• Immunology
• Molecular Biology
• Pharmacology

Background:

• Mangiferin (MF), a xanthone found in herbal medicines, exhibits anti-inflammatory and immunomodulatory properties.
• The precise regulatory effects and mechanisms of mangiferin on cellular pyroptosis are not fully understood.
• Pyroptosis is a highly inflammatory form of programmed cell death implicated in various diseases.

Purpose of the Study:

• To investigate the regulatory effect of mangiferin on lipopolysaccharide (LPS)-induced pyroptosis in mouse bone-marrow-derived macrophages (BMDMs).
• To elucidate the underlying molecular mechanisms by which mangiferin modulates pyroptosis.

Main Methods:

• BMDMs were stimulated with LPS to induce pyroptosis and subsequently treated with varying concentrations of mangiferin (10, 50, 100 μg/mL).
• Cytokine levels (TNF-α, IL-1β, IL-6, IL-18) in cell supernatants were measured using ELISA.
• Gene expression of pyroptosis-related genes (TNF-α, IL-1β, IL-6, IL-18, Caspase-1, Caspase-11, GSDMD) was analyzed by RT-PCR.
• Protein expression of key pyroptosis markers (ASC, NLRP3, caspase-1, caspase-11, GSDMD, NF-κB) was assessed by Western blot.

Main Results:

• Mangiferin significantly inhibited the LPS-induced elevation of secreted and gene expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-18).
• Mangiferin suppressed the gene expression of Caspase-1, Caspase-11, and Gasdermin D (GSDMD).
• Mangiferin decreased the protein levels of NLRP3, caspase-1, caspase-11, full-length GSDMD (GSDMD-FL), cleaved GSDMD (GSDMD-N), and NF-κB.

Conclusions:

• Mangiferin exerts multi-target regulatory effects on inflammation and pyroptosis.
• It inhibits the NF-κB pathway, thereby suppressing inflammatory caspase-mediated pyroptosis.
• Mangiferin reduces GSDMD cleavage, offering a potential therapeutic strategy for inflammatory conditions.