Therapeutic Potential of BM-MSCs Exosomes and Rutin Nanoparticles in Regulating Apoptosis and Inflammation in CFA-induced Arthritis

INTRODUCTION: The toxicity, high cost, and negative side effects of conventional treatments of Rheumatoid Arthritis (RA) highlight the necessity for more effective and safer therapeutic options. METHODS: Rutin-loaded Chitosan/Pectin Nanoparticles (RT-CPN) were synthesized via a modified ionic gelation technique and characterized by various physicochemical methods. Exosomes (EXO) were isolated from mesenchymal stem cells-conditioned media and characterized. Six groups (n = 10) were used to evaluate the treatment's effectiveness in a CFA-induced rat arthritis model. Normal control, arthritic control, and arthritic groups treated with Rutin (RT) (20 mg/kg), EXO (100 μg protein/ rat, weekly i.v.), RT-CPN (20 mg/kg), and RT-CPN+EXO. Treatment lasted 28 days, after which, ankle circumference was recorded, serum and joint tissues were collected for molecular and histopathological analysis. RESULTS: Treatment with RT, EXO, RT-CPN, and EXO+RT-CPN significantly reduced ankle swelling, serum RF, PGE2, ROS, and TNF-α, while increasing IL-4. They also downregulated NF-κB p50, IκBα, TNFR, P53, and caspase-3 expression. Gross morphologically, leg swelling and redness declined, and ankle joint histological investigation showed reduced pannus formation, inflammation, synovial hyperplasia, and cartilage degradation. DISCUSSION: Both EXO and RT-CPN demonstrated potent anti-arthritic effects by regulating inflammation, oxidative stress, and apoptosis (both extrinsic and intrinsic). They worked best together, probably because of their synergy. CONCLUSION: The EXO+RT-CPN combination showed the most potent anti-arthritic effect, mediated by suppressing oxidative stress and by anti-inflammatory and anti-apoptotic mechanisms. This suggests the therapeutic potential of combination therapies in arthritis treatment.