TY - JOUR
T1 - Inhibitory activity of gintonin on inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and collagen-induced arthritis in mice
AU - Kim, Mijin
AU - Sur, Bongjun
AU - Villa, Thea
AU - Nah, Seung Yeol
AU - Oh, Seikwan
N1 - Funding Information:
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 ).
Funding Information:
To further verify the anti-arthritis effect of Gintonin, we then carried out the animal experiment using an arthritis mouse model induced by collagen. The collagen-induced arthritis (CIA) mouse model is one of the most commonly used autoimmune models of rheumatoid arthritis. Like rheumatoid arthritis, erosion of cartilage and bone is a characteristic of CIA [27]. We used the following indicators, body weight, squeaking score, arthritis index, and paw volume to determine the severity of arthritis. The results showed that the pain was slowed down and alleviated by Gintonin. To further support the results of these behavioral experiments, in addition to observing the pannus with H&E staining, changes in the thickness of cartilage were observed using safranin-O staining. The anti-arthritis effect of Gintonin in the histological analysis was consistent with the results of the behavioral experiments. The severity of pannus formation decreased and the erosion of cartilage was also reduced by Gintonin in a dose-dependent manner. Studies using the CIA model have reported that administration of IL-18 promotes the development of corrosive, inflammatory arthritis and IL-18 plays a pro-inflammatory role in rheumatoid arthritis [28]. Another interesting target, G-CSF, was also reported to be a potential treatment target for rheumatoid arthritis [29,30]. Therefore, we measured the expression of IL-6, IL-18, and G-CSF in the serum. As a result, Gintonin decreased the expression of IL-6 and G-CSF, but did not modulate IL-18 levels. Although the reduction effect of IL-18 did not appear, it fully supported the results of the CIA model's behavioral tests and histological analysis. With these, the anti-arthritis effect of Gintonin has been demonstrated in the animal experiment using CIA model.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).
Publisher Copyright:
© 2020
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
KW - arthritis
KW - collagen-induced arthritis
KW - cytokines
KW - gintonin
KW - inflammation
UR - http://www.scopus.com/inward/record.url?scp=85098644495&partnerID=8YFLogxK
U2 - 10.1016/j.jgr.2020.12.001
DO - 10.1016/j.jgr.2020.12.001
M3 - Article
AN - SCOPUS:85098644495
SN - 1226-8453
VL - 45
SP - 510
EP - 518
JO - Journal of Ginseng Research
JF - Journal of Ginseng Research
IS - 4
ER -