Combined cyclosporine A and urolithin A therapy ameliorates murine lupus nephritis

Monotherapies for lupus nephritis (LN) often fail to fully control the disease's hallmark, renal inflammation and immune complex deposition. This study investigates a novel combination therapeutic strategy using urolithin A (UA), a multifaceted anti-inflammatory and antioxidant agent, with cyclosporine A (CsA), an established immunosuppressant. The combination therapy's superior efficacy is evidenced by a robust reduction in immunoglobulin G (IgG) anti-dsDNA levels, with markedly improved renal function. The treatment also effectively mitigated immune complex deposition and multiple inflammatory chemokines, including I309, IL-16, and MIP-3. This alleviated kidney damage and suppressed lymphocyte infiltration. We found that CsA alone was ineffective across the analyzed markers, while UA alone produced only a modest effect, highlighting the complementary action of their combination. These findings underscore the potent anti-inflammatory and antioxidant properties of UA and suggest that combining it with CsA offers a more robust strategy for controlling inflammation and preserving renal integrity in LN. Given the FDA-approved status of CsA and UA's "generally recognized as safe" (GRAS) classification, this combination therapy presents a promising and practical clinical pathway for the treatment of lupus nephritis.