Rhein, An Anthraquinone Drug, Suppresses the NLRP3 Inflammasome and Macrophage Activation in Urate Crystal-Induced Gouty Inflammation

Rhein, an anthraquinone drug, is a widely used traditional Chinese medicine. Rhein is a major bioactive metabolite of diacerein which has been approved for treating osteoarthritis with a good safety profile in humans. Gouty arthritis is an inflammatory disease characterized by urate crystal-induced NLRP3 inflammasome activation with up-regulated caspase-1 protease and IL-1β in macrophages. Inhibition of the NLRP3 inflammasome formation has been considered as a potential therapeutic avenue for treating or preventing many inflammatory diseases. This study aimed to evaluate the anti-inflammatory effects of rhein on gouty arthritis. Rhein within the physiological levels of humans showed no toxicity on the cell viability and differentiation, but significantly decreased the production of IL-1β, TNF-α and caspase-1 protease in urate crystal-activated macrophages. Compared to medium controls, rhein at the therapeutic concentration (2.5μg/mL) effectively inhibited IL-1β production by 47% (P=0.002). Rhein did not a...