Farnesol alleviates inflammatory responses and oxidative stress in Freund's complete adjuvant induced arthritic rat model and associated risk factors of atherosclerosis.

Abstract

This preclinical study aims to evaluate the antiarthritic and therapeutic efficacy of farnesol in a model of Freund's complete adjuvant (FCA)-induced arthritis. Farnesol was administered orally once daily for 15 days at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg in 5% DMSO. Methotrexate (MTX) at 0.75 mg/kg was used as a standard treatment, both alone and in combination with 200 mg/kg farnesol. Hematological tests, paw thickness, body weight, and antioxidative status were measured to assess the protective effects of farnesol. Farnesol significantly increased the enzymatic activity of catalase (CAT) and superoxide dismutase (SOD), as well as the non-enzymatic activity of glutathione (GSH). In addition, farnesol reduced tissue lipid peroxidation and nitric oxide (NO) synthetase activity, which was evident by the reduced levels of oxidative stress markers malondialdehyde (MDA), asymmetric dimethylarginine (ADMA), and nitrite. Farnesol downregulated inflammatory markers, including dimethylarginine dimethylaminohydrolase 1 (DDAH 1), cortistatin (CST), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor (TNF-α), in a dose-dependent manner. These findings suggest that oral administration of farnesol, particularly in combination with MTX, effectively suppresses FCA-induced arthritis by ameliorating oxidative stress and inflammatory markers.