Flaccidoside II ameliorates collagen-induced arthritis in mice

Eur J Pharmacol. 2020 Aug 5:880:173155. doi: 10.1016/j.ejphar.2020.173155. Epub 2020 Apr 30.

Abstract

Flaccidoside II (FLA II), the primary active constituent from Anemone flaccida rhizome, was proven to exert therapeutic effect against collagen-induced arthritis (CIA). In this study, a research based on the CIA mouse model was carried out in order to elucidate its therapeutic mechanisms preliminarily. The mice were immunized with porcine type-II collagen to induce CIA and administrated intragastrically with FLA II daily from day 7-42 of the first collagen immunization. The arthritis scores as reflected by the severity of paw swelling and erythema were significantly reduced in FLA II (32 mg/kg) from day 33 onwards. On day 42, the joints of FLA II-treated mice exhibited obvious reductions of inflammatory cells infiltration, synovial hyperplasia and bone destruction. When the concentration of FLA II was no less than 40 nmol/ml, the treatment notably inhibited T and B lymphocyte proliferative responses. As compared to the model group, in FLA II groups, the serum levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were significantly decreased while those of Th2 type cytokines (IL-4 and IL-10) were clearly enhanced. In addition, FLA II treatment showed little regulatory effect on the levels of Th1 type cytokines (IFN-γ and IL-2). The severity of mice CIA was improved by FLA II, further confirming its potential value for the safe treatment of rheumatoid arthritis. The main mechanisms likely involve the inhibition of lymphocyte proliferation and pro-inflammatory cytokine secretion, and the modulation of Th1/Th2-related cytokine balance in CIA.

Keywords: Collagen-induced arthritis; Cytokine; Flaccidoside II; Th1/Th2.

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Experimental / blood
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Cell Proliferation / drug effects
  • Cytokines / blood
  • Joints / drug effects
  • Joints / pathology
  • Male
  • Mice
  • Saponins / pharmacology
  • Saponins / therapeutic use*
  • Spleen / cytology

Substances

  • 3-O-rhamnopyranosyl-1-2-xylopyranosyl oleanolic acid 28-O-rhamnopyranosyl-1-4-glucopyranosyl-1-6-glucopyranosyl ester
  • Antirheumatic Agents
  • Cytokines
  • Saponins