Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China.
Outpatient Department, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China.
Immunopharmacol Immunotoxicol. 2024 Feb;46(1):86-92. doi: 10.1080/08923973.2023.2253990. Epub 2023 Sep 4.
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and joint damage, leading to pain and reduced joint function. Icariin, a flavonoid compound, has been studied for its potential therapeutic role in RA due to its anti-inflammatory and anti-proliferative effects. Here, we aimed to investigate the action mechanism of icariin in regulating RA.
Fibroblast-like synoviocytes (FLS) were obtained from RA and trauma patients, generating RA-FLS and normal FLS. The cells were treated with varying concentrations of icariin (0, 10, 20, 40, 80 μM). We assessed the effects of icariin on cell proliferation, apoptosis, and levels of inflammatory factors using the CCK-8 assay, flow cytometry, and enzyme-linked immunosorbent assay, qRT-PCR, and western blotting.
Icariin treatment had no significant impact on the cell proliferation of normal FLS. However, it dose-dependently repressed cell proliferation, reduced TNF-α, IL-6, and IL-1β levels, and increased apoptosis in RA-FLS. The expression of GAREM1, p-p38, and p-ERK1/2 was upregulated in RA-FLS, which was reversed by icariin treatment. Overexpression of GAREM1 reversed the inhibitory effects of icariin on cell proliferation and inflammatory factor levels in RA-FLS.
Our findings suggest that icariin treatment can alleviate the development of RA by reducing cell proliferation and inflammation in RA-FLS through the regulation of the GAREM1/MAPK signaling pathway. These results support the potential of icariin as a therapeutic agent for RA treatment. As icariin is safe and well-tolerated in previous studies, further research is warranted to explore its efficacy in clinical settings.
类风湿关节炎（RA）是一种以慢性炎症和关节损伤为特征的自身免疫性疾病，导致疼痛和关节功能下降。淫羊藿苷是一种黄酮类化合物，由于其抗炎和抗增殖作用，已被研究用于 RA 的潜在治疗作用。在这里，我们旨在研究淫羊藿苷在调节 RA 中的作用机制。
从 RA 和创伤患者中获得成纤维样滑膜细胞（FLS），生成 RA-FLS 和正常 FLS。用不同浓度的淫羊藿苷（0、10、20、40、80μM）处理细胞。我们使用 CCK-8 测定法、流式细胞术、酶联免疫吸附试验、qRT-PCR 和 Western blot 评估淫羊藿苷对细胞增殖、凋亡和炎症因子水平的影响。
淫羊藿苷处理对正常 FLS 的细胞增殖没有显著影响。然而，它剂量依赖性地抑制 RA-FLS 的细胞增殖，降低 TNF-α、IL-6 和 IL-1β水平，并增加凋亡。GAREM1、p-p38 和 p-ERK1/2 在 RA-FLS 中的表达上调，淫羊藿苷处理可逆转这一现象。GAREM1 的过表达逆转了淫羊藿苷对 RA-FLS 细胞增殖和炎症因子水平的抑制作用。
我们的研究结果表明，淫羊藿苷通过调节 GAREM1/MAPK 信号通路，减少 RA-FLS 的细胞增殖和炎症，从而减轻 RA 的发展。这些结果支持淫羊藿苷作为 RA 治疗药物的潜力。由于淫羊藿苷在以前的研究中是安全且耐受良好的，因此有必要进一步研究其在临床环境中的疗效。
