Preventive Supplementation with Taif Black Mulberry (Morus nigra) Attenuates Systemic Inflammation, Hepatic Oxidative Stress and Liver Alterations in Rats with Collagen-Induced Rheumatoid Arthritis

Rheumatoid arthritis involves systemic inflammation, immune dysregulation, and oxidative stress, which may contribute to hepatic injury. This study investigated the effects of preventive oral supplementation with Taif black mulberry (Morus nigra) fruit powder on systemic inflammatory, serological, oxidative, and hepatic alterations in rats immunized with type II collagen (collagen-induced arthritis, CIA, model). Thirty-two male Wistar rats were randomly assigned to four groups (n = 8 per group): healthy controls, untreated collagen-induced arthritis (CIA) controls, and two CIA groups receiving freeze-dried Morus nigra fruit powder at doses of 100 and 200 mg/kg/day, respectively. Treatment was initiated on the day of the first immunization (day 0) and continued for eight weeks as part of a preventive experimental design. Immunization was induced with bovine type II collagen emulsified in incomplete Freund’s adjuvant. Serum cytokines, anti-cyclic citrullinated peptide (anti-CCP) antibodies, and liver enzymes were assessed. Hepatic malondialdehyde and antioxidant enzyme activities were measured, and liver histopathology was examined using hematoxylin and eosin and Masson’s trichrome staining. Compared with the healthy controls, the CIA model rats showed higher TNF-α, IL-1β, IL-6, IL-17, anti-CCP, lower IL-10, increased hepatic MDA and serum ALT, AST, and ALP, reduced hepatic superoxide dismutase, catalase, and glutathione peroxidase (GPx) activities, and hepatic histological alterations. Both doses of Morus nigra lowered TNF-α, IL-1β, IL-6, IL-17, anti-CCp, ALT, and ALP and increased antioxidant enzyme activities relative to the untreated CIA rats, whereas significant reductions in hepatic MDA and serum AST were observed only with a higher dose. The higher dose also lowered IL-2, whereas neither dose restored IL-10. Anti-CCP and GPx responses were greater at 200 mg/kg/day than at 100 mg/kg/day. Preventive Morus nigra supplementation attenuated systemic inflammatory, autoimmune, oxidative, and hepatic alterations in the CIA rats. These preclinical findings support the protective effect on systemic and hepatic outcomes. However, further mechanistic investigations and clinical studies are required to establish its efficacy and underlying mechanisms of action.