Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou 325000, Zhejiang Province, PR China.
Department of Nephrology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, PR China.
Life Sci. 2018 Sep 1;208:26-32. doi: 10.1016/j.lfs.2018.07.009. Epub 2018 Jul 6.
Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). Both NF-κB activation and NLRP3 inflammasome activation are implicated in LN pathogenesis, suggesting they are potential targets for LN treatment. Icariin, which is isolated from Chinese medicine Horny Goat Weed (Ying Yang Huo), has been shown to have anti-inflammation activity, and inhibit activations of both NF-κB and NLRP3 inflammasome. In present study, the effects of icariin on LN were evaluated in MRL/lpr mice.
We treated MRL/lpr mice with icariin for 8 weeks and then analyzed the renal function and kidney pathology. We monitored the levels of anti-dsDNA antibody and the deposition of immune complex after icariin treatment. We also detected the macrophage infiltration, NF-κB activation, NLRP3 inflammasome activation and inflammatory cytokine TNF-α production in MRL/lpr mice after icariin treatment.
We found that MRL/lpr mice treated with icariin displayed significantly attenuated the renal disease. Icariin-treated mice showed significantly reduced serum anti-dsDNA antibody level and immune complex deposition. Icariin inhibited NF-κB activation and TNF-α production in MRL/lpr mice. Icariin inhibited CCL2 production and macrophage infiltration in MRL/lpr mice. Finally, icariin suppressed NLRP3 inflammasome activation and IL-1β production in MRL/lpr mice.
Icariin alleviated murine lupus nephritis via inhibiting NF-κB activation and NLRP3 inflammasome activation.
狼疮肾炎（LN）是一种由系统性红斑狼疮（SLE）引起的肾脏炎症性疾病。核因子-κB（NF-κB）的激活和NLRP3 炎性小体的激活都与 LN 的发病机制有关，这表明它们是 LN 治疗的潜在靶点。淫羊藿苷是从中药淫羊藿中分离出来的，具有抗炎活性，能抑制 NF-κB 和 NLRP3 炎性小体的激活。本研究评估了淫羊藿苷对 MRL/lpr 小鼠 LN 的作用。
我们用淫羊藿苷治疗 MRL/lpr 小鼠 8 周，然后分析肾功能和肾脏病理。我们监测了淫羊藿苷治疗后抗 dsDNA 抗体和免疫复合物的沉积水平。我们还检测了淫羊藿苷治疗后 MRL/lpr 小鼠的巨噬细胞浸润、NF-κB 激活、NLRP3 炎性小体激活和炎症细胞因子 TNF-α的产生。
我们发现用淫羊藿苷治疗的 MRL/lpr 小鼠肾脏疾病明显减轻。淫羊藿苷治疗组小鼠血清抗 dsDNA 抗体水平和免疫复合物沉积明显降低。淫羊藿苷抑制 MRL/lpr 小鼠 NF-κB 激活和 TNF-α的产生。淫羊藿苷抑制 MRL/lpr 小鼠 CCL2 的产生和巨噬细胞浸润。最后，淫羊藿苷抑制了 MRL/lpr 小鼠 NLRP3 炎性小体的激活和 IL-1β的产生。
淫羊藿苷通过抑制 NF-κB 激活和 NLRP3 炎性小体的激活，减轻了小鼠狼疮肾炎。
