Safety and Efficacy of Curcumin Analogues in Targeting CFA-induced Arthritis

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation that leads to progressive damage. This condition is marked by immune cell-mediated attacks on the synovial membrane, which leads to the swelling and tenderness of small joints. If unmanaged, these inflammatory processes can lead to cartilage and ligament damage, bone erosion, and a decline in the functionality of affected joints. Objective: The present study aimed to evaluate the acute oral toxicity and anti-rheumatic effects of curcumin analogues in female Wistar rats. Methods: The acute toxicity was assessed using OCED 423 guidelines, and rheumatoid arthritis was induced by injecting 0.1ml of Complete Freund's Adjuvant (CFA) having 1g/ml Mycobacterium tuberculosis. After confirmation of the disease model, treatment was started and continued for 21 days once daily. The anti-rheumatic activity was assessed by measuring paw volume using a digital plethysmometer. Body weight and haematological parameters, such as haemoglobin levels, erythrocyte sedimentation rate, platelet counts, mean corpuscular haemoglobin, red blood cells count, and Creactive protein, were measured. The interleukin-6 levels were also determined. Histopathological studies were performed to validate the changes in the joint tissue. Results: After completion of the study, curcumin analogues did not show any toxic effect after oral administration at a dose of 2000 mg/kg. Treatment with synthesized analogues of curcumin in CFAinduced animals showed a reduction in paw volume. There was a significant improvement in body weight as well as biological markers, such as ESR, CRP, RBC, Hb, MCH, PC, and IL-6. Histopathological observations also supported the macroscopic findings, showing improvements in joint tissues. Conclusion: Hence, it is concluded that curcumin analogues were found to be safe and exhibited anti-rheumatic potential in experimental rats, suggesting their therapeutic role in managing rheumatoid arthritis.