Decrease of Functional Activated T and B Cells and Treatment of Glomerulonephitis in Lupus-Prone Mice Using a Natural...

Area of Science:

• Immunology
• Pharmacology
• Natural Products

Background:

• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease requiring long-term immunosuppressive therapy with adverse effects.
• Novel therapeutic strategies are crucial for managing SLE and improving patient outcomes.

Purpose of the Study:

• To investigate the therapeutic potential of the natural flavonoid astilbin in a mouse model of SLE.
• To evaluate astilbin's efficacy in mitigating disease progression and its underlying mechanisms.

Main Methods:

• Female MRL/lpr mice, a model for SLE, were orally administered astilbin at different disease stages (early and late treatment).
• Evaluated parameters included splenomegaly, lymphomegaly, autoantibody levels, lupus nephritis, serum cytokines (IFN-γ, IL-17A, IL-1β, TNF-α, IL-6), T cell activation, plasma cell populations, mitochondrial membrane potential, and B cell co-stimulatory molecule expression.

Main Results:

• Astilbin treatment significantly reduced splenomegaly, lymphomegaly, autoantibody production, and lupus nephritis in early-treated mice.
• Key pro-inflammatory cytokines (IFN-γ, IL-17A, IL-1β, TNF-α, IL-6) were decreased, alongside reduced activated T cells and plasma cells.
• Astilbin also decreased mitochondrial membrane potential in activated T cells and downregulated CD80/CD86 expression on B cells, with notable effects even in late-stage treatment.

Conclusions:

• The natural flavonoid astilbin demonstrates significant therapeutic potential in mitigating SLE development and progression in MRL/lpr mice.
• Astilbin exerts its effects by reducing inflammation, autoantibody production, and the populations of activated T and B cells.
• Astilbin represents a promising natural product-based therapeutic candidate for systemic lupus erythematosus.