Modified Simiaowan prevents articular cartilage injury in experimental gouty arthritis by negative regulation of STAT3 pathway

Modified Simiaowan (MSW) is a traditional Chinese medicine formula that is composed of six herbs. It has been widely used in the treatment of gouty arthritis. This study was designed to investigate the effect of MSW on gouty arthritis and explore the possible mechanisms. The rat gouty arthritis model was established by intra-articular injection of Monosodium Urate (MSU) crystal, and then treated with MSW for 5 days. The perimeter of the knee joints was measured in a time-dependent manner and serum samples were collected for the detection of TNF-α, IL-1β, and IL-6 protein levels by ELISA. The protein expressions of MMP-3, TIMP-3, STAT3, and p-STAT3 in cartilage tissues and C28/I2 cells were detected by Western blot, and the levels of proteoglycan in primary chondrocytes and cartilage tissues were determined by toluidine blue staining. In addition, AG490 and IL-6 were used in vitro to explore the function of IL-6/STAT3 pathway in the protective effect of MSU. MSW reduced the joint swelling rate in gouty arthritis model and inhibited MSU induced up-regulation of IL-1β, TNF-α, and IL-6 protein levels in serum and synovial fluid. IL-1β induced an increase in p-STAT3 and MMP-3 protein expression in C28/I2 cells, as well as a decrease in TIMP-3. MSW serum inhibited the protein expression changes induced by IL-1β in vitro. Furthermore, inhibition of STAT3 signaling negated the effect of MSW serum on p-STAT3, MMP-3, and TIMP-3 protein levels in C28/I2 cells. MSW also increased the content of proteoglycan significantly both in vivo and in vitro. Our data indicated that MSW protected rats from MSU-induced experimental gouty arthritis and IL-1β/IL-6/STAT3 pathway played an essential role in the protective effect of MSU against GA.