Astragalus polysaccharides ameliorates experimental colitis by regulating memory B cells metabolism

Area of Science:

• Immunology
• Pharmacology
• Gastroenterology

Background:

• Reduced Memory B cells (MBCs) are implicated in ulcerative colitis (UC) pathogenesis, presenting a therapeutic target.
• Astragalus polysaccharide (APS), from Astragalus membranaceus (AM), is a traditional medicine with known immunomodulatory effects.
• The specific mechanism of APS in regulating MBCs for colitis treatment remains unclear.

Purpose of the Study:

• To investigate the efficacy of APS in ameliorating experimental colitis.
• To determine if APS can modulate Memory B cells (MBCs) in the context of colitis.
• To elucidate the underlying molecular mechanisms, particularly mitochondrial metabolism, of APS action.

Main Methods:

• Murine model of colitis induced by dextran sulphate sodium (DSS).
• Treatment of colitis mice with APS for 7 days.
• Assessment of disease activity, colonic pathology, immune cell populations (MBCs, IgA+, Foxp3+, IgG1+, IG2a+, IgG2b+), cytokine levels (IgA, TGF-β1, IL-10, IgG, IgM, IL-6, TNF-α), and mitochondrial activity (Mitotracker red).
• Transcriptomics analysis and validation via quantitative polymerase chain reaction (qPCR) and immunohistochemistry.

Main Results:

• APS significantly reduced disease activity index (DAI) and colonic inflammation.
• APS treatment restored colonic length, elevated beneficial cytokines (IgA, TGF-β1, IL-10), and suppressed pro-inflammatory cytokines (IgG, IgM, IL-6, TNF-α).
• APS increased MBCs, IgA+MBCs, and Foxp3+MBCs while decreasing IgG1+, IG2a+, and IgG2b+MBCs, alongside enhanced mitochondrial metabolism in MBCs.
• Transcriptomics identified mitochondrial metabolism as a key mechanism, with differential expression of genes like BLNK, ALDH1A1, BCL-6, Blimp-1, PAX5, P2X7R, BAFF, BAFFR, CD40, NF-κB, and IL-6.

Conclusions:

• APS effectively ameliorates DSS-induced colitis by restoring MBCs balance.
• The therapeutic effects of APS are potentially mediated through the promotion of mitochondrial metabolism in MBCs.
• These findings highlight APS as a promising therapeutic agent for UC, targeting MBCs and mitochondrial function.