Hesperetin, a flavonoid abundant in citrus fruits and various vegetables, has emerged as a promising phytochemical for the treatment of rheumatoid arthritis (RA). With its strong anti-inflammatory and antioxidant properties, hesperidin offers a multifaceted approach to reducing the symptoms and progression of rheumatoid arthritis. The pathogenesis of RA involves a complex interplay between inflammatory cytokines, immune dysregulation, and oxidative stress. Hesperidin exerts its therapeutic effects by modulating these pathways. This drug prevents the production of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β, thus reducing inflammation and joint damage. Hesperidin shows immunomodulatory effects by modulating the function of immune cells. It inhibits the activity of inflammatory cells such as macrophages and neutrophils, which play an important role in the development of rheumatoid arthritis. In addition, hesperetin inhibits the activation of nuclear factor κB, an important transcription factor involved in the expression of inflammatory genes, and exhibits broad anti-inflammatory effects. Hesperetin supplementation improves clinical symptoms and inflammatory markers in patients with rheumatoid arthritis. Hesperetin is a natural compound obtained from food sources and has fewer side effects than traditional rheumatoid arthritis drugs, making it an attractive alternative or complementary treatment. Hespertin is a promising approach for the treatment of rheumatoid arthritis. Its pleiotropic mechanisms of action, including anti-inflammatory, antioxidant and immunomodulatory effects, have great therapeutic potential to reduce the symptoms of rheumatoid arthritis, stop the progression of the disease and improve the quality of life of patients. This review article highlights the clinical trials needed to fully elucidate the therapeutic benefits of hesperetin and determine its role in the conventional treatment of rheumatoid arthritis.
