Caragana sinica root bioactive fraction ameliorates experimental arthritis by inhibiting synovial inflammatory...

Rheumatoid arthritis (RA) is a chronic autoimmune disease with synovial inflammatory lesions as the initiating factor and pivotal pathogenic driver, triggering persistent inflammation and progressive joint destruction. While Caragana sinica root has long been used in folk medicine for rheumatic disorders, its specific bioactive fractions and therapeutic mechanisms in RA remain unelucidated.

This study aims to evaluate the therapeutic efficacy of the bioactive fraction from Caragana sinica root (CSRBF) against experimental arthritis and clarify its underlying mechanism by identifying core targets and exploring its regulatory effects on fibroblast-like synoviocytes (FLSs).

CSRBF was prepared via 70% ethanol reflux extraction and macroporous resin purification. Adjuvant-induced arthritis (AA) rats model and TNF-α-stimulated FLSs were used to evaluate CSRBF's efficacy. In vivo therapeutic effects were assessed via arthritis index scoring, histological staining, gait analysis, and micro-CT. In vitro, cell proliferation, migration, invasion, and pro-inflammatory cytokine expression were detected. Core targets were identified and verified using LiP-MS, LC-MS, molecular docking, molecular dynamics simulation, and CETSA.

CSRBF dose-dependently alleviated AA severity in rats, reduced synovial hyperplasia, cartilage erosion, and bone destruction, while improving motor function. In vitro, CSRBF inhibited TNF-α-induced FLSs proliferation, migration, invasion, and excessive secretion of pro-inflammatory cytokines. HSP90α was confirmed as the core target of CSRBF, with three active components (hesperetin, pinocembrin, and secoisolariciresinol) directly binding to HSP90α.

CSRBF ameliorates experimental arthritis by targeting HSP90α to inhibit FLSs-mediated synovial inflammation, highlighting it as a promising natural anti-RA candidate and HSP90α as a valuable therapeutic target.