coumestrol and Lupus-Erythematosus--Systemic

Previous study showed that soy isoflavone supplement alleviates disease severity in autoimmune-prone mice. As the ethyl acetate extract of alfalfa sprout (AS) has selective oestrogenic and anti-inflammatory activity, this study evaluated the effects of alfalfa sprout ethyl acetate extract (ASEA) on disease severity of systemic lupus erythematosus, using autoimmune-prone female MRL-lpr/lpr mice. In Experiment 1, five groups of 12-week-old female mice were per oral treated with vehicle (control), lyophilized AS (550 mg wt/kg BW), ASEA (ASEA, 25 mg/kg BW), coumestrol (CUM, 0.075 mg/kg BW) and tamoxifen (TAM, 0.375 mg/kg BW) as the positive control. The onset of proteinuria was delayed, and the life span was significantly longer in the ASEA and TAM groups but neither in the AS nor in the CUM groups, compared to the control. To examine the changes in the immunological parameters related to disease process, three more groups of MRL-lpr/lpr female mice (control, ASEA and TAM) were fed in a similar manner for 6 weeks in the Experiment 2. Flow cytometric analysis of splenocytes showed a significantly lower percentage of activated T cells in the ASEA and TAM groups. The ex-vivo interferon-gamma and interleukin (IL)-4 production from splenocytes and tumour necrosis factor-alpha and IL-1beta production from peritoneal exudate cells were also significantly lower in the ASEA group compared with the control. The ASEA group also had less severe glomerulonephritis. Thus, ASEA attenuated cytokine and inflammatory responses of self-reactive lymphocytes, decreased the disease severity, increased survival and life span of the autoimmune-prone MRL-lpr/lpr mice, suggesting a potential of ASEA in the treatment of autoimmune diseases.

Topics: Acetates; Animals; Autoantibodies; Biomarkers; Coumestrol; Cytokines; Female; Humans; Lupus Erythematosus, Systemic; Male; Medicago sativa; Mice; Mice, Inbred MRL lpr; Phytoestrogens; Plant Extracts; Receptors, Estrogen; Spleen; Survival Rate; Transcriptional Activation

Coumestrol is a naturally occurring plant estrogen. As estrogen influences cellular and humoral immunity, and has known effects on murine models of lupus, we investigated the effect of coumestrol on disease expression in the NZB/W F1 mouse. Female NZB/W F1 mice were fed a "standard" rodent diet including soy proteins, a non-soy diet, or a non-soy diet with 0.01% coumestrol. Outcome measures included survival, autoantibody expression, immunoglobulin levels, proteinuria, renal histology and B cell immunohistochemistry, and renal mRNA expression. At 24 weeks, the treatment group had decreased prevalence of autoantibodies detected by immunofluorescence and less splenomegaly. At 39 weeks, the prevalence of autoantibodies was similar but the treatment group had less proteinuria. Overall, there was little effect of treatment on renal mRNA levels as assessed by gene array analysis, but functional ontology mapping revealed that genes encoding proteins involved in the immune response were most often affected. These results suggest that treatment with coumestrol may ameliorate some aspects of disease progression in this model of systemic autoimmunity.

Topics: Animals; Antibody Formation; Autoantibodies; Autoimmunity; Chromatin; Coumestrol; Disease Models, Animal; Female; Gene Expression; Immunoglobulins; Kidney; Lupus Erythematosus, Systemic; Mice; Mice, Inbred NZB; Oligonucleotide Array Sequence Analysis; Phytoestrogens; RNA, Messenger