Fisetin inhibits pristine-induced systemic lupus erythematosus in a murine model through CXCLs regulation.

Systemic lupus erythematosus (SLE) is associated with an increased risk of vascular complications. Lupus nephritis is a major manifestation of SLE in the clinic. Lupus nephritis is elevated by T helper type 17 (Th17) cells, the major pro‑inflammatory T‑cell subset, leading to autoimmunity modulation. Therapeutic treatments targeting leukocyte recruitment may be useful in attenuating vascular complications linked to SLE progression. 3,7,3',4'‑Tetrahydroxyflavone (fisetin) is a flavonol and a member of the flavonoid polyphenols. It is present in various fruits and vegetables, including persimmons, apples, kiwis, grapes, onions, strawberries and cucumbers. In the present study, the effects of fisetin against SLE induced by pristane (PRI) were evaluated in mice. Fisetin was indicated to reduce PRI‑induced anti‑double stranded DNA, anti‑ small nuclear ribonucleoprotein and the ratio of albumin to creatinine in urine. In addition, the chemokine (C‑X‑C motif) ligand (CXCL) signaling pathway was activated for PRI treatment, which was reversed by fisetin administration by reducing CXCL‑1 and 2, chemokine (C‑C motif) ligand 3, as well as CXC receptor 2 expression. In addition, the induction of inflammatory cytokines, including interleukin (IL)‑6, tumor necrosis factor‑α, IL‑1β, as well as the chemokine interferon‑γ, by PRI were downregulated by fisetin treatment in mice. Furthermore, Th17 cells and their associated cytokines were highly induced by PRI treatment, which was inhibited by fisetin administration. The present results indicated that fisetin may be an effective management for SLE by targeting the CXCL signaling pathway and regulating Th17 differentiation during lupus nephritis development.