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

ABSTRACT

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)-α, interleukin (IL)-1ß 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 RA-dep model rats with HQC. In vitro, the HQC drug-containing serum (HQC-serum) activates the Wnt1/ß-catenin 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.