Awan Sobia Khalid, Sharif Ali, Akhtar Bushra
Department of Pharmacology, Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore, 54000, Pakistan.
Department of Pharmacy, Faculty of Health and Pharmaceutical Sciences, University of Agriculture Faisalabad, Faisalabad, 38000, Pakistan.
Inflammopharmacology. 2025 Aug 13. doi: 10.1007/s10787-025-01907-7.
Rheumatoid arthritis is a persistent immune-mediated inflammatory disorder that primarily affects joint bones, impacting approximately 0.5-1.0% of the global population. People with RA are 1.5 times more likely to develop cardiovascular conditions, including atherosclerosis. This study explored the therapeutic potential of GAc in a rat model of RA induced by CFA, focusing on its impact on biomarkers associated with atherosclerosis. Molecular docking studies indicated strong binding affinities of GAc with key inflammatory cytokines, including TNF-α, IL-6, IL-1β, NF-κB and PRMT-1. The experimental model of 23 days involved the induction of arthritis by injecting 0.15 mL of CFA into the sub-plantar region of the rats' left hind paws. GAc was dissolved in distilled water and administered to rats via oral gavage. Our results revealed that the administration of GAc, particularly in combination with MtxSt (GAc 10 g/kg + MtxSt), significantly (p < 0.001) reduced arthritic scores, joint stiffness scores, paw thickness, levels of lipids (LDL, VLDL, TG, and TC), asymmetric dimethylarginine (ADMA), homocysteine, oxidative stress, and pro-inflammatory cytokines. In addition, GAc markedly (p < 0.001) improved body weight, hematological parameters (RBC, %HCT and Hb), HDL, dimethylarginine dimethylaminohydrolase-1(DDAH-1), and CST levels. Histopathological assessments showed that GAc 10 g/kg + MtxSt significantly alleviated bone and cartilage erosion (p < 0.001), pannus formation (p < 0.001), synovial hyperplasia (p < 0.01), vascular congestion (p < 0.001) and inflammatory cell infiltration (p < 0.001). The therapeutic efficacy of GAc is ascribed to its anti-inflammatory, antioxidant, and anti-atherosclerotic properties. This study suggested that combining GAc with MtxSt exerts a synergistic effect in mitigating inflammation and reducing the risk of atherosclerosis associated with RA.
类风湿性关节炎是一种持续的免疫介导的炎症性疾病，主要影响关节骨骼，全球约0.5 - 1.0%的人口受其影响。类风湿性关节炎患者患心血管疾病（包括动脉粥样硬化）的可能性高出1.5倍。本研究探讨了没食子酸（GAc）在弗氏完全佐剂（CFA）诱导的类风湿性关节炎大鼠模型中的治疗潜力，重点关注其对与动脉粥样硬化相关生物标志物的影响。分子对接研究表明，GAc与关键炎症细胞因子（包括肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β、核因子-κB和蛋白精氨酸甲基转移酶-1）具有很强的结合亲和力。为期23天的实验模型是通过向大鼠左后爪足底皮下注射0.15 mL CFA诱导关节炎。GAc溶解于蒸馏水中，通过灌胃给予大鼠。我们的结果显示，给予GAc，尤其是与甲氨蝶呤-柳氮磺胺吡啶（MtxSt）联合使用（GAc 10 g/kg + MtxSt），显著（p < 0.001）降低了关节炎评分、关节僵硬评分、爪厚度、脂质（低密度脂蛋白、极低密度脂蛋白、甘油三酯和总胆固醇）水平、不对称二甲基精氨酸（ADMA）、同型半胱氨酸、氧化应激和促炎细胞因子水平。此外，GAc显著（p < 0.001）改善了体重、血液学参数（红细胞、红细胞压积百分比和血红蛋白）、高密度脂蛋白、二甲基精氨酸二甲胺水解酶-1（DDAH-1）和胱硫醚-γ-裂解酶（CST）水平。组织病理学评估显示，GAc 10 g/kg + MtxSt显著减轻了骨和软骨侵蚀（p < 0.001）、血管翳形成（p < 0.001）、滑膜增生（p < 0.01）、血管充血（p < 0.001）和炎性细胞浸润（p < 0.001）。GAc的治疗效果归因于其抗炎、抗氧化和抗动脉粥样硬化特性。本研究表明，GAc与MtxSt联合使用在减轻炎症和降低与类风湿性关节炎相关的动脉粥样硬化风险方面发挥协同作用。
