The Mechanism of Jieduquyuziyin Prescription in the Treatment of Systemic Lupus Erythematosus via Nek7-NLRP3 Signaling Pathway

Abstract

This study aimed to investigate the mechanism and partial material basis of Jieduquyuziyin prescription (JQZP) reduces systemic lupus erythematosus (SLE) inflammation via regulating Nek7-NLRP3 signaling pathway. The therapeutic effect of JQZP was evaluated by MRL/lpr SLE mice model in vivo and Lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammation model in vitro. The partial material basis of JQZP was analyzed by network pharmacology, molecular docking and HPLC. The effect of JQZP on inhibiting the Nek7-NLRP3 signaling pathway and the underlying molecular mechanism were investigated by ELISA, RT-qPCR and Western blot. in vivo experiments showed that JQZP could ameliorate renal histopathological changes, decrease spleen index, 24 h urine and urine creatinine (UCR) concentration, and increase urinary microalbumin (ALB) concentration and microalbumin/creatinine ratio (ACR) in MRL/lpr mice. In addition, JQZP down-regulated the levels of pro-inflammatory cytokines IL-18 and IL-1β both in vivo and in vitro. Network pharmacology and HPLC analysis showed that salidroside, luteolin and apigenin in JQZP-medicated serum were partial main active ingredients, and molecular docking showed that all three main active ingredients could bind to Nek7, NLRP3 and ASC well. Western blot further confirmed that JQZP, JQZP-medicated serum and active monomer ingredients could regulate the expression of Nek7, NLRP3, and ASC in Nek7-NLRP3 signaling pathway. JQZP has a certain effect on improving excessive inflammation of SLE, and the mechanism of action may be related to the inhibition of Nek7-NLRP3 signaling pathway. Salidroside, luteolin and apigenin may be partial material basis for exerting this effect.