Objective: Intra-renal T cells and macrophages play a key pathogenic role in the development and progression of glomerular crescents. We aimed to establish (S)-armepavine [(S)-ARM], a major bioactive compound of a Chinese medicinal plant, Nelumbo nucifera, as a potential therapeutic agent in the treatment of autoimmune crescentic glomerulonephritis (ACGN).
Methods: A mouse ACGN model associated with T-cell dysregulation, was used to evaluate the therapeutic effects of (S)-ARM on the rapidly progressive glomerular disorder.
Results: The results showed that (S)-ARM administered in the established phase of ACGN is capable of dramatically decreasing glomerular crescents in the kidney and improving proteinuria and renal dysfunction. These effects were associated with greatly inhibited infiltration of T cells/macrophages and suppressed nuclear factor (NF)-κB activation in the kidney, lowered serum levels of autoantibodies and both serum and intra-renal levels of pro-inflammatory cytokines, suppressed T/B-cell activation and T-cell proliferation of the spleen, reduced glomerular immune deposits and apoptosis in both the spleen and kidney in (S)-ARM-treated ACGN mice, compared with the vehicle-treated (disease control) group of ACGN mice.
Conclusion: We demonstrated therapeutic effects of (S)-ARM on ACGN as a result of: (i) early systemic negative modulation of T/B cells; (ii) intra-renal regulation of combined NF-κB activation and mononuclear leucocytic infiltration, thereby preventing glomerular crescent formation; and (iii) protection from apoptosis in both the spleen and kidney.