[Cheng's Juanbi Decoction Inhibits Rheumatoid Arthritis Pathology by Blocking the WTAP-Wnt7b-Wnt/β-Catenin Signaling Axis].
摘要
Objective: Cheng's Juanbi Decoction (CSJBD) is a classic traditional Chinese medicine formula for treating rheumatoid arthritis (RA), exhibiting significant clinical efficacy, but the underlying mechanisms remain unclear. We investigated whether CSJBD inhibited RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis using a collagen-induced arthritis (CIA) mouse model and fibroblast-like synoviocytes (FLSs) derived from RA patients (RA FLSs) and examined the underlying mechanisms. Methods: #3 + Wnt7b-NC group. To study the underlying mechanism by which CSJBT affected RA FLSs, RA FLSs were divided into the RA FLSs group, the RA FLSs + CSJBDS-M group, the RA FLSs+CSJBDS-M + Wnt7b-OE group, and the RA FLSs+CSJBDS-M + NC group. We used ultra-high performance liquid chromatography (UPLC) to identify and quantify key monomer compounds from CSJBD as quality criteria for CSJBD preparation. Bioinformatics, CCK-8, RT-qPCR, Western blot, immunofluorescence, and related methods were employed to assess the therapeutic efficacy and underlying mechanisms of CSJBD in treating RA. Results: < 0.05), confirming that WTAP regulated the pathway via Wnt7b. According to experimental verification, CSJBD significantly inhibited the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs. Wnt7b overexpression reversed the inhibitory effect of CSJBD on the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs, indicating that Wnt7b is the direct target of CSJBD. Conclusion: CSJBD inhibits RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis, with Wnt7b identified as a direct therapeutic target of CSJBD.