Abstract
Naringenin is flavonoid mainly found in citrus fruits which has shown several biological properties. In this work, we evaluated the therapeutic potential of the flavonoid Naringenin. Five-month-old B6.MRL-Faslpr/J lupus-prone mice were administered daily orally with Naringenin for seven months. We showed that Naringenin treatment at 50 or 100 mg/kg inhibited the splenomegaly and decreased the levels of anti-nuclear and anti-dsDNA autoantibodies. Furthermore, a reduction in serum concentration of TNF-α, IFN-γ and IL-6 was observed in the mice provided with Naringenin. Interestingly, serum levels of IL-10 increased. Naringenin decreased the frequency and absolute numbers of splenic effector memory T cells. Additionally, in order to be able to evaluate whether Naringenin prevented kidney damage, twelve-week-old MRL/MpJ-Faslpr/J mice, an accelerated lupus model, were orally administered with Naringenin at 100 mg/kg for six weeks. Surprisingly, Naringenin treatment prevented kidney damage and reduced the development of fibrosis similar to cyclophosphamide group. Moreover, Naringenin treatment increased the percentage of regulatory T cells in this aggressive model of lupus. Together, these results suggest a potential ability of Naringenin to reduce the autoimmunity in lupus-prone mice by modulation of T-cell subsets and cytokines profile that mitigate the development of important lupus clinical manifestations.
Highlights
Systemic Lupus Erythematosus (SLE) is a chronic disease that is known to predominantly affect women (~9:1 with respect to men)
Naringenin treatment ameliorated the splenomegaly in B6.MRL-Faslpr/J mice
To evaluate the therapeutic potential of Naringenin on SLE, five-month-old B6.MRL-Faslpr/ J mice were orally administered by gavage with 50 or 100 mg/kg daily for seven months and compared with vehicle and cyclophosphamide groups
Summary
Systemic Lupus Erythematosus (SLE) is a chronic disease that is known to predominantly affect women (~9:1 with respect to men). A spontaneous activation of T cells occurs which leads to the expansion of CD4+CD44+CD62L- T effector memory cells [6,7,8]. T cells increase their production of proinflammatory cytokines such TNF-α, IFN-γ and IL-6 [9,10,11]. Regulatory T cells (Tregs) are important in suppression of immune response and prevent autoimmune disorders through different mechanisms including the production of anti-inflammatory cytokines (IL-10, TGF-β) or cell-cell contact [12,13]. Other authors have reported unaltered or increased proportions of Tregs. Other important fact is that effector cells have a reduced sensitivity to suppression by Tregs [17]. B-cell hyperactivity is enhanced by T cells, leading to the constant production of autoantibodies, B cells take up autoantigens and acting as antigen-presenting cells to T cells [18,19]
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