Isorhamnetin attenuates collagen-induced arthritis via modulating cytokines and oxidative stress in mice
1Department of Orthopaedics, Affiliated Hospital of Weifang Medical College Weifang 261053, Shandong, P. R. China.
Abstract:
Inflammation and oxidative stress were involved in the development and progression of rheumatoid arthritis (RA). Isorhamnetin has anti-inflammatory and anti-oxidative activities, but its effects on RA have not been investigated. In order to observe the possible therapeutic effects of isorhamnetin on RA, we established a collagen-induced arthritis mouse model and treated the animal with isorhamnetin for 3 weeks. Besides, fibroblast-like synoviocytes (FLS) were treated with lipopolysaccharide (LPS) and isorhamnetin. The severity of arthritis was assessed by arthritis score, joint destruction score and inflammation score. Levels of cytokines TNF-α, IL-1β, IL-6, IL-17A, IL-17F, IL-10 and IL-35 in the joint tissue homogenate and cell culture medium as well as anti-type II collagen antibody in serum were measured using ELISA. Contents of H2O2 and malondialdehyde (MDA) in joint tissue homogenate were measured using assay kits. We found collagen immunization induced significant arthritis in mice and isorhamnetin at the dose of 10 and 20 mg/kg/day could significantly attenuate the collagen-induced arthritis. Isorhamnetin also modulated the production of cytokines and suppressed the oxidative stress in the mice with collagen-induced arthritis at the dose of 10 and 20 mg/kg/day. These data suggested that isorhamnetin might be a potential agent for the management of RA.
Insights
Isorhamnetin shows potential for rheumatoid arthritis (RA) management. This study found isorhamnetin significantly reduced arthritis severity and suppressed inflammation and oxidative stress in a collagen-induced arthritis mouse model.
Area of Science:
- Immunology
- Pharmacology
- Biochemistry
Background:
- Rheumatoid arthritis (RA) pathogenesis involves inflammation and oxidative stress.
- Isorhamnetin possesses known anti-inflammatory and anti-oxidative properties.
- The therapeutic potential of isorhamnetin in RA remains unexplored.
Purpose of the Study:
- To investigate the therapeutic effects of isorhamnetin on collagen-induced arthritis (CIA) in a mouse model.
- To evaluate the impact of isorhamnetin on inflammatory markers and oxidative stress in RA.
Main Methods:
- A collagen-induced arthritis mouse model was established and treated with isorhamnetin (10 and 20 mg/kg/day) for 3 weeks.
- Fibroblast-like synoviocytes (FLS) were treated with lipopolysaccharide (LPS) and isorhamnetin.
- Arthritis severity, cytokine levels (TNF-α, IL-1β, IL-6, IL-17A, IL-17F, IL-10, IL-35), anti-type II collagen antibodies, H2O2, and MDA were assessed.
Main Results:
- Collagen immunization successfully induced significant arthritis in mice.
- Isorhamnetin treatment (10 and 20 mg/kg/day) significantly attenuated arthritis severity, joint destruction, and inflammation.
- Isorhamnetin modulated pro-inflammatory cytokine production and suppressed oxidative stress markers (H2O2, MDA) in CIA mice.
Conclusions:
- Isorhamnetin demonstrates significant therapeutic potential in mitigating collagen-induced arthritis.
- Isorhamnetin's anti-arthritic effects are associated with its ability to modulate cytokine profiles and reduce oxidative stress.
- Isorhamnetin may serve as a promising agent for the clinical management of rheumatoid arthritis.
