Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China.
Mol Med Rep. 2018 Oct;18(4):3619-3624. doi: 10.3892/mmr.2018.9422. Epub 2018 Aug 22.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly affects patient quality of life. Galangin is an extract with multiple health benefits, including anti‑oxidative, anti‑proliferative, immunoprotective and cardioprotective effects. However, to the best of the authors' knowledge, no detailed studies have investigated its regulatory effects on the nuclear factor (NF)‑κB/NLR family pyrin domain containing 3 (NLRP3) signaling pathway. The present study aimed to investigate the protective mechanism of galangin in RA fibroblast‑like synoviocytes with regards to the NF‑κB/NLRP3 signaling pathway. Human RA fibroblast‑like synovium cells (RAFSCs) were treated with lipopolysaccharide (LPS) to induce inflammation. The levels of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α, IL‑18, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, prostaglandin E2 (PGE2), and nitric oxide (NO) were measured by enzyme‑linked immunosorbent assay or western blotting in the absence or presence of different concentrations of galangin. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were additionally evaluated. Furthermore, factors involved in the NF‑κB/NLRP3 pathway, including NLRP3, apoptosis‑associated speck‑like protein containing A, IL‑1β, pro‑caspase‑1, caspase‑1, phosphorylated (p)‑NF‑κB inhibitor α and p‑NF‑κB, were assessed by western blotting. The results revealed that LPS significantly stimulated IL‑1β, TNF‑α, IL‑18, PGE2, NO, iNOS, COX‑2 and NF‑κB/NLRP3 factor expression, compared with the control. SOD activity was reduced. Pre‑treatment with galangin significantly attenuated the effects of LPS, and galangin was demonstrated to have effective anti‑oxidative properties. In conclusion, galangin protected RAFSCs through downregulation of the NF‑κB/NLRP3 signaling pathway. These findings suggested that galangin may provide a novel direction for the development of RA therapies in the future.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，严重影响患者的生活质量。高良姜素是一种具有多种健康益处的提取物，具有抗氧化、抗增殖、免疫保护和心脏保护作用。然而，据作者所知，尚无详细研究调查其对核因子（NF）-κB/NLR 家族富含吡啶结构域的 3（NLRP3）信号通路的调节作用。本研究旨在探讨高良姜素对 NF-κB/NLRP3 信号通路的类风湿关节炎成纤维样滑膜细胞（RAFS）的保护机制。用人脂多糖（LPS）诱导 RA 成纤维样滑膜细胞（RAFS）炎症。通过酶联免疫吸附试验或 Western blot 法在有无不同浓度高良姜素的情况下，检测白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α、IL-18、诱导型一氧化氮合酶（iNOS）、环氧化酶（COX）-2、前列腺素 E2（PGE2）和一氧化氮（NO）的水平。此外，还评估了超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。还通过 Western blot 法检测 NF-κB/NLRP3 通路相关因子，包括 NLRP3、凋亡相关斑点样蛋白包含 A、IL-1β、前胱天蛋白酶-1、胱天蛋白酶-1、磷酸化（p）-NF-κB 抑制剂 α 和 p-NF-κB。结果表明，与对照组相比，LPS 显著刺激了 IL-1β、TNF-α、IL-18、PGE2、NO、iNOS、COX-2 和 NF-κB/NLRP3 因子的表达，SOD 活性降低。高良姜素预处理显著减弱了 LPS 的作用，且高良姜素具有有效的抗氧化作用。结论：高良姜素通过下调 NF-κB/NLRP3 信号通路保护 RAFS。这些发现表明，高良姜素可能为未来 RA 治疗提供新的方向。
