Evidence to support testing of resveratrol for efficacy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of multiple joints with the potential to cause joint destruction and functional disability. While the effects can be seen in many tissues and organs, attacks are primarily against the synovial joints. Resveratrol, a phytoalexin found in grape skins and other plants, has been shown to exhibit anti-proliferative, anti-inflammatory, and anti-catabolic properties. Studies have suggested that these properties can be harnessed to reduce the effects associated with rheumatoid arthritis. This review will focus on the mechanisms involved in the development of rheumatoid arthritis, and the inhibitory effects of resveratrol. The risk factors involved in rheumatoid arthritis such as elevated cytokines: tumor necrosis factor-α (TNF-α), and Interleukin 1β (IL-1β); activation of the NF-κB signaling cascade; and enhanced cyclooxygenase-2 (COX-2) activity will be addressed. Mechanisms of resveratrol-induced inhibition of nuclear factor-κB (NF-κB) activation and IL-1β production will be discussed, as well as resveratrol's induction of COX-2 nuclear accumulation and subsequent apoptosis. Resveratrol induces nuclear accumulation of COX-2 facilitating apoptosis. Finally, the potential role of inducible COX-2-dependent apoptosis in arthritis relief will be investigated.