Therapeutic potential of fucoidan from a persian gulf alga (Sargassum tenerrimum) in rheumatoid arthritis: In vivo evaluation in a rat model.

Abstract

Fucoidan, due to its anti-inflammatory and immune-modulating effects, shows promise for the treatment of rheumatoid arthritis (RA). This study tested fucoidan from the Persian Gulf algae Sargassum tenerrimum on adjuvant-induced RA in Wistar rats. The isolated fucoidan demonstrated excellent scavenging capability (83.66 ± 0.35%) on 2,2-diphenyl-1-picrylhydrazyl radicals at a dosage of 6 mg/mL. RA was induced in rats via Freund's adjuvant injection. From days 5 to 23, rats (n = 10/group) received daily fucoidan (50, 100, 150 mg/kg) or prednisolone (10 mg/kg). Fucoidan effectively reduced inflammation and alleviated symptoms associated with adjuvant-induced RA in a dose-dependent manner. Hematoxylin and eosin staining strongly supported the previous results regarding fucoidan's effectiveness, especially at 150 mg/kg, in reducing inflammation and repairing joint structure. Safranin O staining confirmed that better joint and cartilage health was linked to higher fucoidan doses. Immunohistochemical analysis showed that fucoidan treatment significantly lowered levels of the inflammatory cytokines IL-1β and TNF-α in the joint tissue of RA rats. Moreover, fucoidan treatment led to a dose-dependent reduction in inflammatory biomarkers, including myeloperoxidase, nitric oxide, malondialdehyde, and C-reactive protein. In the joint tissue. Fucoidan reduced the activity of inflammatory genes (T-bet, RORγt), leading to decreased differentiation of Th1 and Th17 cells, while enhancing the activity of GATA3 and FOXP3, promoting Th2 and Treg cell polarization. In contrast to prednisolone, fucoidan elevated Nrf2 and HO-1 levels in the plantar joint. Fucoidan from S. tenerrimum has strong antioxidant and immunomodulatory properties, making it a promising option for managing complex inflammation, such as RA.