Wu Bin, Dong Qinyan, Zhang Qin, Jin Fangqin, Weng Jiangping
Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314000, Zhejiang, China.
Clin Rheumatol. 2025 Mar;44(3):1041-1056. doi: 10.1007/s10067-024-07261-3. Epub 2025 Feb 5.
BACKGROUND/RATIONALE: Rheumatoid Arthritis (RA) is a prolonged autoimmune condition marked by persistent inflammation, causing joint damage and bone erosion. Catalpol (CAT), an iridoid glycoside, offers anti-inflammatory benefits, warranting its study in RA models.
To investigate the anti-inflammatory effects of CAT in RA by evaluating its impact on cellular and animal RA models.
In vitro biological actions of CAT were investigated by the methods of cell viability, proliferation, migration, invasion, apoptosis, ROS generation, double luciferase reporter assay for NF-κB-p65 activity, Nitrite release detection, and RT-qPCR for gene expression in Tumor Necrosis Factor-alpha (TNF-α)-induced Human Fibroblast-Like Synoviocytes from RA patients (HFLS-RA) (cellular RA model). Arthritis severity, joint cellular structure, gene expression, inflammatory factors, and joint inflammation studies were investigated in mice with collagen-induced arthritis (CIA) (animal RA model).
CAT treatment groups showed significant improvements (P < 0.001) in cell viability, migration, invasion, and apoptosis compared to the TNF-α-induced group. ROS generation and the activity of NF-κB-p65 were significantly reduced (P < 0.001). Nitrite release was decreased (P < 0.01, P < 0.001) in CAT-treatment groups. Pro-inflammatory and bone-metabolizing cytokine gene expression was markedly downregulated (P < 0.05, P < 0.001) in the cellular RA model. CIA mice treated with CAT exhibited significantly reduced arthritis severity, paw edema, and arthritis index (P < 0.05, P < 0.01). Joint pathology scores showed improvement (P < 0.001) in CAT-treatment groups. In the animal RA model, bone-metabolizing and inflammatory cytokine gene expression was significantly reduced in CAT-treatment groups (P < 0.01, P < 0.001).
CAT effectively reduces RA's inflammation and bone metabolism issues, suggesting its potential as a therapeutic agent for RA treatments. Key Points • Plant-derived Catalpol compound is an effective choice for rheumatoid arthritis treatment due to its anti-inflammatory potential. • CAT's effects were tested on TNF-α-induced HFLS-RA cells and in CIA mice, assessing cell viability, apoptosis, ROS generation, arthritis severity, inflammatory factors, and joint inflammation studies. • The administration of CAT could greatly enhance cell health and reduce inflammation markers and arthritis symptoms. • Observed significant reduction of RA inflammation and bone issues, confirming CAT as a therapeutic agent in RA treatment.
背景/原理：类风湿关节炎（RA）是一种慢性自身免疫性疾病，其特征为持续炎症，可导致关节损伤和骨质侵蚀。梓醇（CAT）是一种环烯醚萜苷，具有抗炎作用，因此值得在RA模型中进行研究。
通过评估梓醇对细胞和动物RA模型的影响，研究其在RA中的抗炎作用。
采用细胞活力、增殖、迁移、侵袭、凋亡、活性氧生成、双荧光素酶报告基因检测NF-κB-p65活性、亚硝酸盐释放检测以及逆转录定量聚合酶链反应（RT-qPCR）检测肿瘤坏死因子-α（TNF-α）诱导的类风湿关节炎患者来源的人成纤维样滑膜细胞（HFLS-RA）中的基因表达等方法，研究梓醇的体外生物学作用（细胞RA模型）。在胶原诱导性关节炎（CIA）小鼠中研究关节炎严重程度、关节细胞结构、基因表达、炎症因子和关节炎症（动物RA模型）。
与TNF-α诱导组相比，梓醇治疗组在细胞活力、迁移、侵袭和凋亡方面有显著改善（P < 0.001）。活性氧生成和NF-κB-p65活性显著降低（P < 0.001）。梓醇治疗组亚硝酸盐释放减少（P < 0.01，P < 0.001）。在细胞RA模型中，促炎和骨代谢细胞因子基因表达明显下调（P < 0.05，P < 0.001）。用梓醇治疗的CIA小鼠关节炎严重程度、爪肿胀和关节炎指数显著降低（P < 0.05，P < 0.01）。梓醇治疗组关节病理评分有所改善（P < 0.001）。在动物RA模型中，梓醇治疗组骨代谢和炎症细胞因子基因表达显著降低（P < 0.01，P < 0.001）。
梓醇可有效减轻RA的炎症和骨代谢问题，表明其作为RA治疗药物的潜力。要点：• 植物来源的梓醇化合物因其抗炎潜力是类风湿关节炎治疗的有效选择。• 在TNF-α诱导的HFLS-RA细胞和CIA小鼠中测试了梓醇的作用，评估了细胞活力、凋亡、活性氧生成、关节炎严重程度、炎症因子和关节炎症。• 梓醇的给药可显著改善细胞健康状况，降低炎症标志物和关节炎症状。• 观察到RA炎症和骨问题显著减轻，证实梓醇为RA治疗的药物。
