Mahmoud Ahmed Mostafa, Alfadl Esam Mohamed Abu, Ahmed Ahmed R H, Abouelella Azza M A, Alshazly Omar, Mohamed Mamdouh F A, Allaf Hasan El, Allam Rasha M
Department of Physiology, Faculty of Medicine, Sohag University, Sohag, Egypt.
Department of Basic Medical Sciences, Aqaba Medical Sciences University, Aqaba, Jordan.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 29. doi: 10.1007/s00210-025-03823-7.
Rheumatoid arthritis (RA) is one of the most common systemic autoimmune inflammatory diseases, with a progressive etiology that results in serious complications and a higher chance of early death. Visfatin, an adipokine, is correlated with disease pathologic features and becomes a key biomarker and therapeutic target for RA. This study aimed to evaluate the anti-arthritic activity of metformin (an antidiabetic drug with anti-inflammatory activities) and methotrexate (the first choice for disease-modifying antirheumatic drugs in RA, with diverse adverse effects) in complete Freund's adjuvant (CFA)-induced arthritis in female rats. Treatment outcomes were assessed using arthritis severity, serum levels of inflammatory markers, and pro-inflammatory adipokine (visfatin). In addition to radiological and histopathological examination, and docking analysis. Results showed that Met, MTX, and Met/MTX significantly (p ≤ 0.05) lowered paw swelling and arthritic score, as well as attenuated serum levels of rheumatoid factor (RF), C-reactive protein (CRP), and visfatin. The combined treatment gives the best results. The previously mentioned findings were further confirmed through radiological and histopathological examinations. In conclusion, the co-administration of metformin could potentiate the anti-arthritic activity of methotrexate, providing a medical strategy for arthritis management.
类风湿性关节炎（RA）是最常见的全身性自身免疫性炎症性疾病之一，其病因呈进行性发展，会导致严重并发症和较高的早期死亡几率。内脂素作为一种脂肪因子，与疾病病理特征相关，成为类风湿性关节炎的关键生物标志物和治疗靶点。本研究旨在评估二甲双胍（一种具有抗炎活性的抗糖尿病药物）和甲氨蝶呤（类风湿性关节炎中改善病情抗风湿药物的首选，有多种不良反应）对完全弗氏佐剂（CFA）诱导的雌性大鼠关节炎的抗关节炎活性。使用关节炎严重程度、炎症标志物血清水平和促炎脂肪因子（内脂素）来评估治疗效果。此外，还进行了放射学和组织病理学检查以及对接分析。结果表明，二甲双胍、甲氨蝶呤以及二者联合用药均显著（p≤0.05）降低了 paw 肿胀和关节炎评分，并降低了类风湿因子（RF）、C 反应蛋白（CRP）和内脂素的血清水平。联合治疗效果最佳。上述结果通过放射学和组织病理学检查得到进一步证实。总之，二甲双胍与甲氨蝶呤联合使用可增强甲氨蝶呤的抗关节炎活性，为关节炎治疗提供了一种医学策略。 （注：原文中“paw swelling”中的“paw”可能是“足爪”之意，但放在这里感觉表述不太准确，不过按要求未做修改直接翻译了）
