Pedunculoside attenuates pathological phenotypes of fibroblast-like synoviocytes and protects against collagen-induced arthritis.

Abstract

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-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. 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-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. 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.

• Authors: X Ma, G Chen, J Wang, J Xu, F Zhao, M Hu, Z Xu, B Yang, J Guo, S Sun, M Liu
• Journal: Scandinavian journal of rheumatology (Scand J Rheumatol) Vol. 48 Issue 5 Pg. 383-392 (Sep 2019) ISSN: 1502-7732 [Electronic] England
• PMID: 31354003 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Drugs, Chinese Herbal
• Triterpenes
• Deoxycytidine
• pedunculoside
• 5-ethyl-2'-deoxycytidine
• Glucose

Topics

• Animals
• Arthritis, Experimental (diagnosis, drug therapy, metabolism)
• Cell Proliferation
• Cells, Cultured
• Cytokines (metabolism)
• Deoxycytidine (analogs & derivatives, metabolism)
• Drugs, Chinese Herbal
• Female
• Fibroblasts (drug effects, metabolism, pathology)
• Flow Cytometry
• Glucose (analogs & derivatives, pharmacology)
• Phenotype
• Radiography
• Rats
• Rats, Wistar
• Synovial Membrane (metabolism, pathology)
• Triterpenes (pharmacology)