ラットにおける完全フロイントアジュバント誘発関節炎に対するピラゾリン誘導体の抗関節炎作用の可能性

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 mL) into their right hind paw. Animals were divided into 6 groups (n = 4): normal, arthritis, standard drug (methotrexate 1 mg/kg intraperitoneally), and 3 treatment groups receiving 5-E-5-H-PD, 10, 20 and 40 mg/kg orally for 21 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 mg/kg dose animals decreased significantly to 2.31 ± 0.12 mm compared to 4.82 ± 0.14 mm in the disease animals (p < 0.001). Arthritis scores reduced from 3.8 ± 0.2 (control) to 1.5 ± 0.3 in the high-dose treatment group. Serum IL-10, TNF-α, and NF-κB levels were significantly reduced to 66.75 ± 3.0 pg/mL, 34.50 ± 1.8 pg/mL and 9.50 ± 0.6 pg/mL respectively, compared to the arthritis induced rats 129.8 ± 2.0 pg/mL, 77.75 ± 1.5 pg/mL and 28.50 ± 1.3 pg/mL respectively, compared to the arthritis induced rats (112.3 ± 5.5, 96.8 ± 4.3, 123.1 ± 6.2 pg/mL, p < 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.