Huangqin Qingre Chubi Capsule improves rheumatoid arthritis accompanied depression through the Wnt1/ß-catenin signaling pathway

Aim of the study: Research on the mechanism of Huangqin Qingre Chubi Capsules (HQC) in improving rheumatoid arthritis accompanied depression (RA-dep) model rats. Methods: We employed real -time qPCR (RT-qPCR), western blotting (WB), confocal microscopy, bioinformatics, and other methods to investigate the anti-RA-dep effects of HQC and its underlying mechanisms. Results: HQC alleviated the pathological indexes of inflammation and depression in RA-dep model rats, decreased the levels of tumor necrosis factor (TNF)-a, interleukin (IL) -1 ss and IL -6, increased the levels of norepinephrine (NE) and serotonin (5-HT), and improved the injury of hippocampus. The analysis of network pharmacology suggests that HQC may target the Wnt/ ss- catenin pathway in the treatment of RA-dep. Furthermore, molecular dynamics simulations revealed a strong affinity between HQC and the Wnt1 molecule. RT-qPCR and Western Blot (WB) experiments confirmed the critical role of the Wnt1/ ss- catenin signaling pathway in the treatment of RAdep model rats with HQC. In vitro, the HQC drug-containing serum (HQC-serum) activates the Wnt1/ ss- cat- enin signaling pathway in hippocampal cells and, in conjunction with Wnt1, ameliorates RA-dep. In summary, HQC exerts its anti-inflammatory and antidepressant effects in the treatment of RA-dep by binding to Wnt1 and regulating the Wnt1/ ss- catenin signaling pathway. Conclusions: HQC improved the inflammatory reaction and depression-like behavior of RA-dep model rats by activating Wnt1/ ss- catenin signal pathway. This study revealed a new pathogenesis of RA-dep and contributes to the clinical promotion of HQC in the treatment of RA-dep.