Opportunities and challenges associated with rheumatoid arthritis: The role of natural polyphenol products

RA is a chronic inflammatory disease commonly found in industrialized nations, characterized by ongoing joint destruction. Its pathogenesis involves a complex interaction between the innate and adaptive immune systems, resulting in the excessive production of inflammatory mediators. These mediators contribute to various chronic diseases, including RA, which necessitates drug interventions to regulate their release. Herbal plants have historically been a rich source of bioactive compounds with therapeutic potential, many of which are now widely used as medications. Treatments for RA focus on inhibiting oxidative stress, downregulating pro-inflammatory cytokines such as IL-1, IL-6, TNF-α, and NF-κB, suppressing matrix metalloproteinases that damage cartilage, enhancing antioxidant activity, and modulating macrophage phenotypes. Flavonoids, a subclass of polyphenols, stand out for their antioxidant and anti-inflammatory properties. They help alleviate RA by inhibiting the production of inflammatory cytokines, reducing oxidative stress, suppressing the proliferation of lymphocytes and synovial cells, inducing apoptosis, and regulating energy metabolism. This review emphasizes the potential of natural polyphenols, primarily flavonoids, as promising candidates for RA treatment, providing insights into their mechanisms and the prospects for future drug development.