Emodin alleviates joint inflammation and bone erosion in rats with collagen-induced arthritis by inhibiting ferroptosis and degrading matrix metalloproteinases

Abstract

To investigate the osteoprotective mechanism of emodin in light of the ferroptosis signaling pathway in a rat model of rheumatoid arthritis. SD rat models of collagen-induced arthritis (CIA) were treated with methotrexate or low or high doses of emodin, and the changes in arthritis scores and toe volume were recorded. model of CIA rats. Malondialdehyde (MDA) content in the joint cartilage was determined, and ankle joint tissue pathologies were observed using caffein solid green staining and hematoxylin-spermine red staining. MMP3 and MMP13 expressions in the ankle joint tissues were detected using immunohistochemistry, and Western blotting was used to detect the protein expressions of ACSL4, SLC7A11, GPX4, and FTH1. Compared with the normal control rats, the CIA rats showed significantly increased arthritis score index with obvious toe swelling (P<0.05), rough cartilage surface, and loss and irregular aligment of chondrocytes. The rat models also showed significantly increased MDA and ACSL4 contents, lowered SLC7A11, GPX4, and FTH1 contents (P<0.05), and decreased expressions of MMP3 and MMP13 in the ankle joint (P<0.05). The rat models treated with either methotrexate or emodin (40 and 80 mg/kg) had significantly reduced arthritis score index and toe swelling with smooth cartilage surface and neat arrangement of the chondrocytes. The treatments with methotrexate and emodin both decreased the contents of MDA and ACSL4 and increased the contents of SLC7A11, GPX4, and FTH1 in the joint tissues (P<0.05). Emodin can effectively control joint inflammation and improve joint bone erosion in CIA rats possibly by inhibiting the ferroptosis signaling pathways and reducing the expressions of MMP3 and MMP13.