Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University , Nanjing , China.
School of Biomedical Sciences, University of Western Australia , Perth , Australia.
Scand J Rheumatol. 2019 Sep;48(5):383-392. doi: 10.1080/03009742.2019.1600716. Epub 2019 Jul 29.
: The discovery of alternative and well-tolerated anti-arthritic drugs, especially from natural products, is becoming an area of active research. Pedunculoside (PE) is a novel triterpene saponin extracted from the dried bark of Thunb. Limited published papers have reported its pharmacological properties, including anti-inflammatory, anti-myocardial ischaemia, anti-liver injury, and hypocholesterolaemic activities. However, the effect of PE on rheumatoid arthritis (RA) remains unknown. Here, we investigated the anti-arthritic effect of PE in both in vitro and in vivo models. : The inhibitory effects of PE on proliferation, migration, and production of inflammatory mediators in primary fibroblast-like synoviocytes (FLSs) were examined by a 5-ethynyl-2'-deoxyuridine incorporation assay, wound-healing assay, and real-time polymerase chain reaction, respectively. Cellular signalling mechanisms were analysed by Western blot. The in vivo studies were performed using a collagen-induced arthritis (CIA) rat model. Multiple methods, including arthritis scoring, enzyme-linked immunoassay, radiography, and histopathological assessment, were used to evaluate the therapeutic effects of PE on CIA rats. : The in vitro studies revealed that PE significantly inhibited proliferation and migration of FLSs. PE also decreased the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, and tumour necrosis factor-α (TNF-α). Western blot results suggested that PE suppressed TNF-α-stimulated activation of p38 and extracellular signal-regulated kinase. The in vivo studies showed that PE treatment significantly inhibited synovial inflammation and bone destruction in CIA rats. : These results demonstrate that PE exerts an inhibitory role in FLSs and CIA rats, and therefore may have therapeutic value for the treatment of RA.
: 从天然产物中寻找替代的、耐受性良好的抗关节炎药物，尤其是医学专业学术文献，已成为一个活跃的研究领域。 杠柳苷（PE）是从杠柳的干燥树皮中提取的一种新型三萜皂苷。已有有限的文献报道了其药理学特性，包括抗炎、抗心肌缺血、抗肝损伤和降胆固醇作用。然而，PE 对类风湿关节炎（RA）的影响尚不清楚。在这里，我们研究了 PE 在体内和体外模型中的抗关节炎作用。 : 通过 5-乙炔基-2'-脱氧尿苷掺入试验、划痕愈合试验和实时聚合酶链反应分别检测 PE 对原代成纤维样滑膜细胞（FLSs）增殖、迁移和炎症介质产生的抑制作用。通过 Western blot 分析细胞信号通路。采用胶原诱导关节炎（CIA）大鼠模型进行体内研究。采用关节炎评分、酶联免疫吸附试验、放射学和组织病理学评估等多种方法评估 PE 对 CIA 大鼠的治疗作用。 : 体外研究表明，PE 显著抑制 FLSs 的增殖和迁移。PE 还降低了促炎细胞因子的产生，包括白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）、白细胞介素 8（IL-8）和肿瘤坏死因子-α（TNF-α）。Western blot 结果表明，PE 抑制了 TNF-α 刺激的 p38 和细胞外信号调节激酶的激活。体内研究表明，PE 治疗可显著抑制 CIA 大鼠滑膜炎症和骨破坏。 : 这些结果表明，PE 在 FLSs 和 CIA 大鼠中发挥抑制作用，因此可能对治疗 RA 具有治疗价值。
