Abstract
Background:
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, synovial hyperplasia, and systemic complications. Current treatment options have side effects and limitations, leading to a growing interest in alternative therapies.

Aim:
This study investigates the therapeutic potential of jellyfish collagen (JC) on collagen-induced arthritis (CIA) in a rat model.

Methods:
Twenty-eight male Sprague Dawley rats were randomly assigned to four groups: negative control (G1), positive control with RA but no treatment (G2), and two experimental groups treated with 200 µg/kg (G3) and 100 µg/kg (G4) of JC. Arthritis was induced using bovine type II collagen emulsified in complete Freund’s adjuvant. Paw swelling was assessed and photographed twice weekly. JC was administered orally from day 26 to day 31 post-immunization. Histopathological analyses were conducted on joints, liver, and spleen. Oxidative stress markers (MDA), glutathione peroxidase (GPx) activity, and the expression of inflammatory and apoptotic genes (Nf-κb, Il-1β, Tnfα, Cox-2, Jak1, Stat3, Tgf-β, Il-10, Bcl-2, Caspase-3) were assessed using molecular techniques.

Results:
JC treatment significantly reduced arthritis scores, with the lower dose (100 µg/kg) having the most significant effect. Histological analysis showed reduced tissue damage in the joints, liver, and spleen. JC treatment exhibited antioxidant properties, as shown by the reduction in oxidative stress markers (MDA) and the increase in glutathione peroxidase (GPx) activity in the liver and kidney. Additionally, JC exhibited anti-inflammatory effects, as confirmed by reduced Nf-κb levels in the ankle joint and the transcription levels of inflammation-related genes in the spleen, including Nf-κb, Il-1β, Tnfα, Cox-2, Jak1, and Stat3, were down-regulated, while the transcription levels of anti-inflammatory related genes, such as and Tgf-β and Il-10, were up-regulated. Moreover, JC showed an anti-apoptotic effect, as indicated by increased transcription level of Bcl-2 gene and decreased Caspase-3 (Cas3) gene transcription level in the spleen

Conclusion:
Our research suggests that JC might be a useful therapeutic treatment for RA because of its anti-inflammatory, antioxidant, and anti-apoptotic properties, particularly at the lower dose of 100 µg/kg.

Key words: Rheumatoid arthritis; Jellyfish collagen; Oxidative stress; Inflammation; Apoptosis.