Therapeutic Potential of BM-MSCs Exosomes and Rutin Nanoparticles in Regulating Apoptosis and Inflammation in...

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.

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.

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.

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.

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.