Citrus limon and Paradisi Fruit Peel Hydroethanolic Extracts Prevent the Progress of Complete Freund’s Adjuvant-Induced Arthritis in Male Wistar Rats

This study was designed to assess the preventive effect of Citrus limon (C. lemon) and Citrus paradisi (C. paradisi) fruit peel hydroethanolic extracts on the progress of complete Freund’s Adjuvant (CFA)-induced arthritis in male Wistar rats. Rheumatoid arthritis rat model was established by subcutaneous injection of 0.2 ml CFA into the right hind paw of each rat at two successive days. Arthritic rats were administered C.limon and C. paradisi fruit peel hydroethanolic extracts by oral gavage of 100 mg/kg body weight /day for 9 and 18 days. Administration of C. limon and C. paradisi fruit peel hydroethanolic extracts for 9 and 18 days, significantly reduced the CFA-induced paw swelling and edema in arthritic rats as manifested by a significant decrease in right hind paw circumference, volume and thickness. The increased mRNA expression of right ankle joint pro-inflammatory and inflammatory mediators including cyclooxygenase-1 (COX-1), interleukin-1β (IL-1β) and interleukin-6(IL-6) and the decreased mRNA expression of anti-inflammatory cytokine(IL-4) were significantly improved in arthritic rats by oral administration of C. limon and C. paradisi fruit peel hydroethanolic extracts. In association, the deleterious histological alterations represented by articular joint inflammatory cells infiltration, fibroblasts proliferation, edema, synovial hyperplasia, pannus formation and cartilage necrosis as well as spleen haemorrhage and lymphocytic necrosis and thymus lymphoblasts proliferation were noticeably alleviated by oral supplementation of arthritic rats with C. limon and C. paradisi fruit peel hydroethanolic extracts for 9 and 18 days. The study suggested that C. limon and C. paradisi fruit peel hydroethanolic extracts have anti-arthritic potentials which may be mediated via their anti-inflammatory activities.