Mechanistic Evaluation of Antiarthritic Effects of Eupatilin in CFA-Induced Arthritic Rats: An in Vivo and in Silico Study

In the present study, we explored the antiarthritic potential of Eupatilin on complete Freund's adjuvant (CFA)-induced arthritis rats. In order to induce arthritis in the Sprague-Dawley rats, CFA vaccination was used, and Eupatilin was given to the rats at dose of 5, 10, and 20 mg/kg. Various biochemical and other parameters were studied to define the pharmacological benefit of Eupatilin. The study's findings revealed that Eupatilin increases rats’ body weight and significantly reduces hind paw volume. It also improves the antioxidant status of CFA rats by lowering malondialdehyde levels and increasing the concentration of endogenous antioxidants superoxide dismutase and GPx. Eupatilin also improved hematological markers, which were demonstrated to be altered in CFA rats as compared to the control. In the Eupatilin-treated group, the level of pro-inflammatory cytokines was found to be reduced as compared to CFA rats. In a molecular docking analysis, it showed favorable interaction with the active site of cyclooxygenase-2 (COX-2) by the formation of numerous nonbonded interactions by interacting with Cys32, Leu138, Pro 139, Val141, Ala142, and Cys145. It also showed a Vina score of −9.4 and interacts with the cavity volume of 4435 Å3. Eupatilin showed favorable antiarthritic benefits in the CFA-induced arthritis model, as evidenced by reductions in paw volume, significant weight loss prevention, and maintenance of the healthy hematological and biochemical profile may be through inhibiting COX-2.