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Inhibitory activity of gintonin on inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and collagen-induced arthritis in mice

  • Kim, Mijin (Department of Molecular Medicine, School of Medicine, Ewha Womans University) ;
  • Sur, Bongjun (Department of Molecular Medicine, School of Medicine, Ewha Womans University) ;
  • Villa, Thea (Department of Molecular Medicine, School of Medicine, Ewha Womans University) ;
  • Nah, Seung Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Oh, Seikwan (Department of Molecular Medicine, School of Medicine, Ewha Womans University)
  • Received : 2020.04.22
  • Accepted : 2020.12.01
  • Published : 2021.07.01

Abstract

Background: Gintonin is a newly derived glycolipoprotein from the roots of ginseng. The purpose of this study is to investigate the anti-arthritic efficacy of Gintonin on various proteases and inflammatory mediators that have an important role in arthritis. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β 1 hour later. The antioxidant effect of Gintonin was measured using MitoSOX and H2DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators using RT-PCR, western blot, and ELISA. The phosphorylation of mitogen-activated protein kinase (MAPK) pathways and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus were also analyzed using western blot, ELISA, and immunocytochemistry. Collagen-induced arthritis (CIA) mice model was used. Mice were orally administered with Gintonin (25, 50, and 100 mg/kg) every 2 days for 45 days. The body weight, arthritis score, squeaking score, and paw volume were measured as the behavioral parameters. After sacrifice, H&E and safranin-O staining were performed for histological analysis. Results: Gintonin significantly inhibited the expression of inflammatory intermediates. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. Moreover, Gintonin suppressed the symptoms of arthritis in the CIA mice model. Conclusion: As a result, the antioxidant and anti-inflammatory effects of Gintonin were demonstrated, and ultimately the anti-arthritic effect was proved. Collectively, Gintonin has a great potential as a therapeutic agent for arthritis treatment.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning (MRC, 2010-0029355).

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