Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India.
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India.
Eur J Pharmacol. 2021 May 15;899:174044. doi: 10.1016/j.ejphar.2021.174044. Epub 2021 Mar 18.
The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway has recently emerged as a novel therapeutic target in treating various diseases. Therefore, the present study aimed to assess the protective role of the Nrf2 activator, dimethyl fumarate (DMF) in the complete Freund's adjuvant (CFA)- induced arthritis model. DMF (25, 50, and 100 mg/kg) and dexamethasone (2 mg/kg) were orally administered for 14 days. Pain-related tests, paw volume, and arthritic scores were measured weekly. Serum TNF-α, IL-1β, cyclic citrullinated peptide (CCP), C-reactive protein (CRP), and rheumatoid factor (RF) levels were estimated. Nitrite, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), catalase (CAT), and myeloperoxidase (MPO) levels were also evaluated. NF-κB, Nrf2, HO-1, and COX-2 levels were estimated in the joint tissue. DMF treatment exerted anti-arthritic activity by enhancing the nociceptive threshold, improving arthritis scores, and reducing paw edema. Also, DMF suppressed changes in oxidative stress markers and inflammatory mediators and enhanced Nrf2 and HO-1 levels in CFA-injected rats. These findings indicate that the anti-arthritic activity of DMF may be mediated by the activation of the Nrf2/HO-1 pathway, which reduced oxidative damage and inflammation.
核因子红细胞 2 相关因子 (Nrf2) 信号通路最近成为治疗各种疾病的新的治疗靶点。因此，本研究旨在评估 Nrf2 激活剂富马酸二甲酯 (DMF) 在完全弗氏佐剂 (CFA) 诱导的关节炎模型中的保护作用。DMF（25、50 和 100mg/kg）和地塞米松（2mg/kg）口服给药 14 天。每周测量疼痛相关测试、爪体积和关节炎评分。估计血清 TNF-α、IL-1β、环瓜氨酸肽 (CCP)、C 反应蛋白 (CRP) 和类风湿因子 (RF) 水平。还评估了亚硝酸盐、丙二醛 (MDA)、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GPx)、谷胱甘肽 (GSH)、过氧化氢酶 (CAT) 和髓过氧化物酶 (MPO) 水平。还评估了关节组织中的 NF-κB、Nrf2、HO-1 和 COX-2 水平。DMF 治疗通过提高痛觉阈值、改善关节炎评分和减轻爪水肿来发挥抗关节炎作用。此外，DMF 抑制了氧化应激标志物和炎症介质的变化，并增强了 CFA 注射大鼠中 Nrf2 和 HO-1 的水平。这些发现表明，DMF 的抗关节炎活性可能是通过激活 Nrf2/HO-1 通路介导的，该通路减轻了氧化损伤和炎症。
