Volume 10,Issue 4
10-Deacetylbaccatin III Alleviates Inflammation by Inhibiting NF-κB in the Joints of AIA Mice
Objective: To evaluate the therapeutic potential of 10-deacetylbaccatin III (10-DAB) in rheumatoid arthritis (RA) and to determine whether its anti-inflammatory effects are mediated through inhibition of the NF-κB signaling pathway. Methods: CFA-induced AIA mice received vehicle, 10-DAB (30 or 120 mg kg⁻¹) or DEX for 28 d; paw swelling, clinical score and body weight were recorded every 48 h. Knees were stained (H&E/TRAP) for synovitis and osteoclasts; serum cytokines (TNF-α, IL-6, IL-10) were quantified by ELISA; spleen p-p65, p-IκBα, iNOS and MMP-3 by Western blot. LPS-stimulated RAW264.7 macrophages were treated with 10-DAB or DEX; viability (CCK-8) and NF-κB activation were assessed. Results: 10-DAB dose-dependently alleviated paw swelling and clinical scores, preserved cartilage and decreased TRAP-positive osteoclasts. It significantly decreased serum TNF-α/IL-6, elevated IL-10, suppressed IκBα/p65 phosphorylation, blocked p65 nuclear import and down-regulated iNOS/MMP-3 in spleen. In RAW264.7 cells, non-toxic 10-DAB inhibited LPS-induced IκBα/p65 phosphorylation and TNF-α release. Conclusion: 10-DAB ameliorates AIA by blocking the NF-κB cascade and downstream inflammatory mediator production, indicating its potential as a candidate for RA therapy.
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