Rutin alleviates lupus nephritis by inhibiting T cell oxidative stress through PPARγ.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by complex clinical symptoms and multi-organ damage. One of the most prevalent complications of SLE is lupus nephritis (LN). Rutin, a natural flavonoid compound found in various plants used in traditional Chinese medicine, has shown promising anti-inflammatory, antioxidant, and renal protective effects. In our study, we treated MRL/lpr mice, a model known for spontaneously developing LN, with Rutin. Our findings reveal that Rutin markedly reduced serum cytokine and autoantibody levels and decreased inflammatory cell infiltration in renal tissues, thereby ameliorating kidney pathology. In vitro experiments indicated that Rutin's therapeutic effect on LN is linked to its significant reduction of oxidative stress in T cells. Further investigations suggest that Rutin enhances oxidative stress management through the modulation of Peroxisome proliferator-activated receptor gamma (PPARγ). We observed that Rutin modulates PPARγ activity, leading to reduced transcriptional activity of NF-κB and STAT3, which in turn inhibits the secretion of inflammatory cytokines such as IL-6, TNF-α, and IL-17. In summary, Rutin can exert an antioxidant effect by regulating PPARγ and shows therapeutic action against LN.

Luteolin attenuates lupus nephritis by regulating macrophage oxidative stress via HIF-1α pathway.

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) and a leading cause of mortality. Luteolin (LUT), a compound found in many vegetables, fruits, and Chinese herbal medicine, has been shown to possess anti-inflammatory, antioxidant, and immunosuppressive properties. However, the mechanisms underlying LUT's potential therapeutic effects on LN remain unclear. In this study, we investigated LUT's antagonistic effects on inflammation and oxidative stress using MRL/lpr mice and H2O2-treated macrophages (Raw264.7). Our results indicate that LUT can ameliorate pathological abnormalities and improve renal function in MRL/lpr mice by reducing renal oxidative stress and urinary protein levels. Furthermore, we found that the Hypoxia-inducible factor 1α (HIF-1α) pathway is involved in the process of LUT improving renal injury in lupus mice. Analysis of GEO data confirmed that HIF-1α expression is significantly elevated in the kidneys of LN patients, and our experiments conducted in vitro and in vivo indicate that infiltrating macrophages contribute to the elevated levels of HIF-1α expression in the kidney. By inhibiting HIF-1α expression and oxidative stress in macrophages, LUT can mitigate renal damage caused by infiltrating macrophages. In conclusion, our findings suggest that LUT may serve as a potential therapeutic option for the prevention and treatment of LN by suppressing HIF-1α expression in macrophages.