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111 Development of artemisinin analogueanalog SM934 in the treatment of systemic lupus erythematosus
  1. J Zuo and
  2. W Tang
  1. Shanghai Institute of Materia Medica- Chinese Academy of Sciences, Immunopharmacology, Shanghai, China

Abstract

Background and aims Besides their outstanding antimalarial activity, artemisinin and its derivatives also possess immunosuppressive activities and are clinical used to treat SLE. β-aminoarteether maleate (SM934), a water soluble artemisinin derivative, got the approval documents authorised by Chinese FDA for clinical trials. This study investigated the curative effects of SM934 on lupus-prone mice and explored its underlying therapeutic mechanisms.

Methods In vivo, SM934 was given orally to female NZB/W F1 and MRL/lpr mice; renal injury, peripheral lymphoid organ disease and serological changes were evaluated. Meanwhile, correlative pathological mechanisms were studied using different aged mice. Besides, the effects of SM934 on human PBMCs were also assessed.

Results We demonstrated that SM934 treatment could significantly improve SLE syndrome in lupus-prone animal models, including delayed the progression of glomerulonephritis; ameliorated proteinuria and renal lesion severity; increased the survival rate; decreased levels of BUN and serum anti–double-stranded DNA antibodies. Furthermore, clinical improvement was accompanied with decreased Th1-related anti- dsDNA IgG2a and IgG3 Abs, serum IL-17, and increased Th2-related anti-dsDNA IgG1 Ab, serum IL-10 and IL-4. Moreover, SM934 could significantly inhibit both of Th1 and Th17 responses, elevate Treg percentage and lower the percentage of CD3+ B220+ CD4- CD8- (double negative) T cells in MRL/lpr mice. We further elucidate that SM934 treatment restored the compartment of B cells in the spleen of MRL/lpr mice by increasing quiescent B cells, maintaining germinal centre B cells, decreasing activated B cells and reducing PCs.

Conclusions This work provides new evidence and clues for research about artemisinin compounds in the field of autoimmune diseases.

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