Wang Ying, Zhao Xiangzhuo, Wang Jingxu, Zhu Xiaoli
Department of Endocrine Nephrology, The First Affiliated Hospital of Xingtai Medical College (Xingtai First Hospital), Xingtai, Hebei Province, 054001, People's Republic of China.
Department of Rheumatic Immunology, Xingtai People's Hospital, Xingtai, Hebei Province, 054000, People's Republic of China.
J Inflamm Res. 2024 Nov 15;17:8839-8852. doi: 10.2147/JIR.S476824. eCollection 2024.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent joint inflammation, pain, and tissue degradation. This study evaluates the therapeutic potential of Norisoboldine (NOR), an isoquinoline alkaloid from Lindera aggregata, in a rat model of RA.
Rats were divided into five groups: normal control (G1), RA model (G2), NOR-treated groups at 15 mg/kg (G3) and 30 mg/kg (G4), and methotrexate-treated group (G5). NOR's anti-arthritic effects were assessed by measuring clinical arthritis scores and inflammatory markers (RF, CRP, TNF-α, IL-6, IL-10). Oxidative stress markers (MDA, SOD, catalase, GPx) and pathways (NF-κB/IKKβ and Nrf2/Keap1) were also evaluated. Histopathology assessed synovial inflammation and tissue degradation.
NOR treatment significantly reduced arthritis severity, as evidenced by decreased clinical arthritis scores and inflammatory markers in RA rats. NOR also exhibited strong antioxidant effects, demonstrated by decreased MDA levels and enhanced SOD, catalase, and GPx activities. NOR further downregulated matrix metalloproteinases (Mmp-2, Mmp-3), aggrecanases (Adamts-4, Adamts-5), and PCNA expression. Histopathology confirmed marked reductions in synovial inflammation and tissue damage in NOR-treated groups.
These findings suggest that NOR's anti-inflammatory and antioxidant properties contribute to reducing both inflammation and the overall severity of RA. NOR's multifaceted actions support its potential as a novel therapeutic agent for RA.
NOR demonstrates protective effects in RA rats by reducing inflammation, oxidative stress, and extracellular matrix degradation, offering promise as a therapeutic option to manage RA pathology comprehensively.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征为持续性关节炎症、疼痛和组织退化。本研究评估了去甲异波尔定（NOR），一种来自乌药的异喹啉生物碱，在RA大鼠模型中的治疗潜力。
将大鼠分为五组：正常对照组（G1）、RA模型组（G2）、15mg/kg NOR治疗组（G3）、30mg/kg NOR治疗组（G4）和甲氨蝶呤治疗组（G5）。通过测量临床关节炎评分和炎症标志物（RF、CRP、TNF-α、IL-6、IL-10）评估NOR的抗关节炎作用。还评估了氧化应激标志物（MDA、SOD、过氧化氢酶、GPx）和信号通路（NF-κB/IKKβ和Nrf2/Keap1）。组织病理学评估滑膜炎症和组织退化情况。
NOR治疗显著降低了关节炎严重程度，RA大鼠的临床关节炎评分和炎症标志物降低证明了这一点。NOR还表现出强大的抗氧化作用，MDA水平降低以及SOD、过氧化氢酶和GPx活性增强证明了这一点。NOR进一步下调了基质金属蛋白酶（Mmp-2、Mmp-3）、聚集蛋白聚糖酶（Adamts-4、Adamts-5）和PCNA的表达。组织病理学证实NOR治疗组滑膜炎症和组织损伤明显减轻。
这些发现表明，NOR的抗炎和抗氧化特性有助于减轻RA的炎症和整体严重程度。NOR的多方面作用支持其作为RA新型治疗药物的潜力。
NOR通过减轻炎症、氧化应激和细胞外基质降解，对RA大鼠具有保护作用，有望成为全面管理RA病理的治疗选择。
