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.

Shi L ，Yuan Z ，Liu J ，Cai R ，Hasnat M ，Yu H ，Feng J ，Wang Z ，Zhao Q ，Wu M ，Huang X ，Shen F ，Yin L ，Yu Y ，Liang T ... -  《-》

Suppressive effect of modified Simiaowan on experimental gouty arthritis: an in vivo and in vitro study.

Shi L ，Xu L ，Yang Y ，Song H ，Pan H ，Yin L ... -  《-》

Traditional Chinese Medicine Formula "Xiaofeng granules" suppressed gouty arthritis animal models and inhibited the proteoglycan degradation on chondrocytes induced by monosodium urate.

Xiaofeng Granules (XF) is a kind of granules prepared by the famous traditional Chinese medicine formula for its efficiency in treating gouty diseases. We investigated the relevance between XF that made from Modified simiaowan (MSW) as the anti-gouty arthritis drugs and protective mechanisms for cartilage matrix in order to provide the evidence for new drug application. In the present study, we evaluated the anti-gouty arthritis activity of XF in rats and rabbits models induced by MSU together with chondrocytes focusing on the link to proteoglycan degradation in vitro studies. The results demonstrated that XF significantly reduced the swelling rate and attenuated the pathological changes in joints. The XF-containing serum were used medicated serum in cellular experiments. The in vitro data were in accordance with the in vivo results, showing that the constituents in XF-containing serum had obvious inhibitory effects on the activation of pro-inflammatory mediators in chondrocytes. Moreover, XF-containing serum substantially inhibited MSU-induced expression of glycosaminoglycans(GAG) and hydroxyproline(Hyp), and up regulated proteoglycan, which might be associated with the regulation of the balance of MMP-3/TIMP-1and ADAMTS-4/TIMP-3 inchondrocytes. In conclusion, XF that made from MSW showed obvious effects on acute gouty arthritis, which also provided an effective protection on cartilage matrix degradation.

Shi L ，Zhao F ，Zhu F ，Liang Y ，Yang F ，Zhang G ，Xu L ，Yin L ... -  《-》

Matrix Metalloproteinase-3 induces proteoglycan degradation in gouty arthritis model.

Gout is an inflammatory arthritis resulting from precipitation of monosodium urate (MSU) crystals in joints and surrounding tissues. However, the mechanism underlying high levels of uric acid inducing gouty arthritis has not been clarified. The purpose was to investigate the role of Matrix Metalloproteinase-3 (MMP-3) in the development of gouty arthritis from hyperuricemia. MSU crystal-induced gouty arthritis model and chondrocytes were used to evaluate changes of MMP-3 levels. Western blot, qPCR and ELISA were performed to detect MMP-3, Tissue Inhibitors of Metalloproteinase-1 (TIMP-1) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs-4 (ADAMTS-4) expressions in rabbit chondrocytes. Expression of proteoglycan was determined through toluidine blue staining. Concentrations of glycosaminoglycan, Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) in chondrocytes were assessed via ELISA kits. Concentration of uric acid in supernate was tested by Automatic Analyzer. MMP-3 was significantly increased in rat serum, synovial fluid, cartilages and chondrocytes treated with high-level uric acid. Increased concentration of glycosaminoglycancould be observed in chondrocytes incubated with MMP-3, as well as the remarkable downregulation of proteoglycan expression. Furthermore, high-level uric acid contributed to the degradation of proteoglycan via the activation of MMP-3. IL-6, IL-1β and TNF-α concentrations were increased significantly in 35 °C compared to 37 °C with MMP-3 and high-level uric acid. Our study showed that MMP-3 was enhanced by high levels of uric acid, which promoted proteoglycan degradation, and induced MSU crystallization in turn. A low temperature environment is an important factor in the development of gout.

Shi L ，Liang T ，Yang F ，Zhu FF ，Liu J ，Jiang JQ ，Wu XW ，Chen AS ，Yuan DP ，Liang XL ... -  《-》

Anti-inflammatory and antinociceptive effects of Chinese medicine SQ gout capsules and its modulation of pro-inflammatory cytokines focusing on gout arthritis.

Shuang-Qi gout capsule is a traditional Chinese medicine prescription, which has been used in the treatment of joint pain, inflammation and gout arthritis. This study evaluates anti-inflammatory and antinociceptive effects of Shuang-Qi gout capsule and its modulation of pro-inflammatory cytokines with special reference to gout arthritis. Anti-inflammatory effect of Shuang-Qi gout capsule was investigated bymice tail-flick response, acetic acid induced writhing response, Xylene-induced auricle inflammation and the hind paw volume of the monosodium urate (MSU) crystal induced rats with different time durations. To investigate the effects on gout arthritis, ankle joint of rats induced by MSU crystals and assessed for edema and histopathological changes. In vitro, prepared serum was incubated with urate crystal induced HUVE cells and the release of TNF-α and IL-1β determined by ELISA. Shuang-Qi gout capsule showed significant and dose dependent anti-inflammatory effect via reducing edema and pain, throughout all the models. The high dose of Shuang-Qi gout capsule and Indomethacin significantly attenuated the edema. Histopathological results showed that high and medium dose of Shuang-Qi gout capsule and Indomethacin reduced gouty joint inflammatory features, while the high dose of Shuang-Qi gout capsule showed a better therapeutic effect. High and medium dose of Shuang-Qi gout capsule significantly reduced the release of TNF-α and IL-1β (p<0.05). Shuang-Qi gout capsule can effectively inhibit the inflammation, analgesia, through the modulation of emission of pro-inflammatory cytokines and the curative effect is dose dependent. Conversely, these MSU induced in vivo and in vitro studies of Shuang-Qi gout capsule suggest that, Shuang-Qi gout capsule may be a potential agent for treatment in gouty arthritis.

Kodithuwakku ND ，Pan M ，Zhu YL ，Zhang YY ，Feng YD ，Fang WR ，Li YM ... -  《-》