Wang Yu-Ling, Gao Ju-Mei, Xing Li-Zhi
Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi 276003, Shandong, China.
Department of Rheumatology and Immunology, Yishui Central Hospital, Linyi 276400, Shandong, China.
Int Immunopharmacol. 2016 Nov;40:294-299. doi: 10.1016/j.intimp.2016.09.006. Epub 2016 Sep 16.
Excessive inflammation contributes greatly to the pathogenesis and development of rheumatoid arthritis (RA). Oroxylin A (OA) is a natural anti-inflammatory flavonoid compound. In this study, we investigated the effects of OA on collagen-induced arthritis (CIA) and human RA fibroblast-like synoviocytes (FLS). CIA was induced in DBA/1 mice and mice were intraperitoneally treated with OA (10mg/kg) for 10days. Arthritis severity was evaluated every day and the histopathologic examination of joints was done. Serum levels of anti-collagen II antibodies (anti-CII Abs) and cytokines were determined by ELISA. Frequency of regulatory T cells (Tregs) and Th17 cells in draining inguinal lymph nodes (ILN) was quantified by flow cytometry. FLS from patients with active RA were treated with varying doses of oroxylin A, followed by stimulation with tumor necrosis factor (TNF)-α (10ng/mL). The production of cytokines was measured by ELISA. Signal transduction proteins were examined by western blot. OA significantly diminished the arthritis and histological damage. Serum anti-CII Abs, IL-1β, IL-6, TNFα, and IL-17 were significantly diminished by OA treatment. Analysis of CD4+T cell populations in OA-treated mice showed an increase in Tregs and reduction in Th17 cells in the ILN. In vitro, OA decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RA FLS in a dose-dependent manner. TNFα-induced p38 MAPK, ERK1/2 and NF-κB signaling pathways were suppressed by OA. Our results indicate that OA exerts an anti-inflammatory activity and may have therapeutic potential for human RA.
过度炎症在类风湿关节炎（RA）的发病机制和发展过程中起很大作用。木犀草素A（OA）是一种天然的抗炎类黄酮化合物。在本研究中，我们调查了OA对胶原诱导的关节炎（CIA）和人RA成纤维样滑膜细胞（FLS）的影响。在DBA/1小鼠中诱导CIA，并对小鼠腹腔注射OA（10mg/kg），持续10天。每天评估关节炎严重程度并对关节进行组织病理学检查。通过酶联免疫吸附测定（ELISA）测定血清中抗Ⅱ型胶原抗体（抗-CII Abs）和细胞因子水平。通过流式细胞术定量引流腹股沟淋巴结（ILN）中调节性T细胞（Tregs）和Th17细胞的频率。用不同剂量的木犀草素A处理活动性RA患者的FLS，然后用肿瘤坏死因子（TNF）-α（10ng/mL）刺激。通过ELISA测量细胞因子的产生。通过蛋白质免疫印迹法检测信号转导蛋白。OA显著减轻了关节炎和组织学损伤。OA处理显著降低了血清抗-CII Abs、IL-1β、IL-6、TNFα和IL-17水平。对OA处理小鼠的CD4+T细胞群体分析显示，ILN中Tregs增加而Th17细胞减少。在体外，OA以剂量依赖性方式降低TNFα刺激的RA FLS中IL-1β和IL-6的分泌。OA抑制了TNFα诱导的p38丝裂原活化蛋白激酶（MAPK）、细胞外信号调节激酶1/2（ERK1/2）和核因子κB（NF-κB）信号通路。我们的结果表明，OA具有抗炎活性，可能对人类RA具有治疗潜力。
