期刊
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
卷 48, 期 5, 页码 383-392出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/03009742.2019.1600716
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资金
- National Natural Science Foundation of China [31870895, 31171135]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP)
- Australian National Health and Medical Research Council (NHMRC), University of Western Australia Research Collaboration Awards [1107828, 1027932]
Objectives: 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 Ilex rotunda 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. Method: 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-2MODIFIER LETTER PRIME-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. Results: 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-1 beta (IL-1 beta), IL-6, IL-8, and tumour necrosis factor-alpha (TNF-alpha). Western blot results suggested that PE suppressed TNF-alpha-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. Conclusion: 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.
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