Effect and Mechanism of Quercetin on Experimental Autoimmune Uveitis in Rats Based on Wnt/β-catenin Signaling Pathway / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo investigate the effects and mechanism of quercetin on experimental autoimmune uveitis （EAU） by regulating the Wnt/β-catenin signaling pathway. MethodThe regulatory relationship between quercetin and EAU was preliminarily determined by network pharmacology. The model was identified by enzyme-linked immunosorbent assay（ELISA） and clinical grading score. The important inflammatory factors， including interleukin（IL）-6 and tumor necrosis factor（TNF）-α in the signaling pathway were detected by ELISA. The binding of important targets in the pathway was verified by molecular docking. The protein and mRNA expression levels of related targets in the signaling pathway were detected by Western blot and Real-time polymerase chain reaction（Real-time PCR）， respectively. ResultAs evaluated by ELISA and the clinical grading score， the model was properly induced. The results of ELISA showed that the levels of IL-6 and TNF-α were the highest in the model group and the dimethyl sulfoxide （DMSO） group， and decreased after medium- and high-dose drug interventions， but the changing tend was the same. Molecular docking showed that the binding energies of quercetin to β-catenin and LRP6 were ideal. Western blot revealed that the expression of β-catenin and LRP6 was the highest in the model group， and decreased with drug intervention at different doses， but the changing trend was the same. Besides， there was no significant difference between the low-dose group and the high-dose group. Real-time PCR results showed that the expression of β-catenin，MYC，AXIN2， and TCF was the highest in the model group，the lowest in the high-dose group， and decreased in the low-dose group. There was no significant difference between the high-dose group and the low-dose group. ConclusionQuercetin can reduce the inflammatory expression of EAU and relieve the pain of patients by regulating the Wnt/β-catenin signaling pathway.