Therapeutic potential of 6-BIO in modulating oxidative stress and inflammation in rheumatoid arthritis.

BACKGROUND

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, oxidative stress, and dysregulated immune responses that culminate in progressive joint destruction. Fibroblast-like synoviocytes (FLS) acquire an aggressive, invasive phenotype, while peripheral blood mononuclear cells (PBMCs) perpetuate inflammatory responses. 6-Bromoindirubin-3′-oxime (6BIO) has been shown to modulate signalling pathways associated with inflammation, oxidative stress, and immune cell activation, processes that are critically dysregulated in RA. This study evaluates the mechanistic effects of 6BIO on pathogenic FLS behaviour and PBMC-mediated immune regulation in RA. METHODS AND

RESULTS

Primary cultures of FLS were established from synovial tissues of patients with RA and controls. In addition, peripheral blood samples were collected from 14 RA patients and 10 healthy blood donors. RA-FLS and PBMCs were treated with 6BIO followed by assessment of fibroblasts migration, ROS levels, Nrf2 localization, antioxidant protein expression, MMP2/9 activity, antioxidant gene expression, T-cell subsets and cytokine levels. 6BIO significantly inhibited RA-FLS migration, reduced MMP2 and MMP-9 levels, suppressed ROS, promoted Nrf2 nuclear translocation, and upregulated antioxidant genes including HO-1 and NQO1. In PBMCs, 6BIO significantly increased CD4+ CD25+ FoxP3+ regulatory T cells, lowered IL-1/TNF-α, and elevated IL-4/IL-13 cytokines.

CONCLUSIONS

Our findings demonstrate that 6BIO modulates key pathogenic processes in RA by exerting anti-migratory, antioxidant, and immunomodulatory effects, thereby supporting its therapeutic potential for rheumatoid arthritis.