Anti-Arthritic Potential of Pyrazoline Derivative Against Complete Freund's Adjuvant Induced Arthritis in Rats.

Abstract

This research explored the potential of a synthesised pyrazoline derivative 5-ethoxy 5-hydroxy 3-methyls 4, 5-dihydro 1Hpyrazol 1 yl (pyridine 4 yl) methanone [5-E-5-H-PD], against arthritis using a Complete Freund's Adjuvant (CFA)-induced arthritis in a rat model. Sprague-Dawley rats were used to induce arthritis via subplantar injection of CFA (0.1&#x2009;mL) into their right hind paw. Animals were divided into 6 groups (n&#x2009;=&#x2009;4): normal, arthritis, standard drug (methotrexate 1&#x2009;mg/kg intraperitoneally), and 3 treatment groups receiving 5-E-5-H-PD, 10, 20 and 40&#x2009;mg/kg orally for 21&#x2009;days. Clinical signs (paw volume and arthritis score), pro-inflammatory cytokines, and histopathological alterations were evaluated. The 5-E-5-H-PD groups showed a reduction in paw edema in a dose-dependent manner. On day 21, paw volume in the 40&#x2009;mg/kg dose animals decreased significantly to 2.31&#x2009;&#xb1;&#x2009;0.12&#x2009;mm compared to 4.82&#x2009;&#xb1;&#x2009;0.14&#x2009;mm in the disease animals (p&#x2009;<&#x2009;0.001). Arthritis scores reduced from 3.8&#x2009;&#xb1;&#x2009;0.2 (control) to 1.5&#x2009;&#xb1;&#x2009;0.3 in the high-dose treatment group. Serum IL-10, TNF-&#x3b1;, and NF-&#x3ba;B levels were significantly reduced to 66.75&#x2009;&#xb1;&#x2009;3.0 pg/mL, 34.50&#x2009;&#xb1;&#x2009;1.8 pg/mL and 9.50&#x2009;&#xb1;&#x2009;0.6 pg/mL respectively, compared to the arthritis induced rats 129.8&#x2009;&#xb1;&#x2009;2.0 pg/mL, 77.75&#x2009;&#xb1;&#x2009;1.5 pg/mL and 28.50&#x2009;&#xb1;&#x2009;1.3 pg/mL respectively, compared to the arthritis induced rats (112.3&#x2009;&#xb1;&#x2009;5.5, 96.8&#x2009;&#xb1;&#x2009;4.3, 123.1&#x2009;&#xb1;&#x2009;6.2&#x2009;pg/mL, p&#x2009;<&#x2009;0.001). Histopathology analysis confirmed reduced synovial hyperplasia and inflammatory infiltration in treated joints. The pyrazoline derivative, 5-E-5-H-PD, demonstrated significant anti-arthritic effects in the CFA-induced rat model by reducing inflammation, cytokine expression and joint destruction. These findings support further investigation into pyrazoline-based compounds as promising therapeutic agents for RA.