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

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-1 β , TNF- α and caspase-1 protease in urate crystal-activated macrophages. Compared to medium controls, rhein at the therapeutic concentration (2.5 μ g/mL) effectively inhibited IL-1 β production by 47% ( P=0.002 ). Rhein did not affect the mRNA levels of CASP1, NLRP3 and ASC, but suppressed the protein expression and enzyme activity of caspase-1. Immunofluorescence confocal microscopy further revealed that rhein suppressed the aggregation of ASC speck and inhibited the formation of NLRP3 inflammasome. Rhein of 5 μ g/mL significantly decreased the ASC speck to 36% ( P=0.0011 ), and reduced the NLRP3 aggregates to 37.5% ( P=0.014 ). Our data demonstrate that rhein possesses pharmacological activity to suppress caspase-1 protease activity and IL-1 β production by interfering with the formation of NLRP3 multiprotein complex. These results suggest that rhein has therapeutic potential for treating NLRP3 inflammasome-mediated diseases such as gouty arthritis.
PMID: 30612459 [PubMed - as supplied by publisher]

Source: The American Journal of Chinese Medicine - January 7, 2019 Category: Complementary Medicine Authors: Chang WC, Chu MT, Hsu CY, Wu YJ, Lee JY, Chen TJ, Chung WH, Chen DY, Hung SI Tags: Am J Chin Med Source Type: research