School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
China Pharmaceutical University, Nanjing, 210009, China.
J Ethnopharmacol. 2021 Apr 24;270:113825. doi: 10.1016/j.jep.2021.113825. Epub 2021 Jan 15.
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.
改良四妙丸（MSW）是一种中药配方，由六种草药组成。它已被广泛用于治疗痛风性关节炎。
本研究旨在探讨 MSW 对痛风性关节炎的作用，并探讨可能的机制。
通过关节内注射尿酸单钠（MSU）晶体建立大鼠痛风性关节炎模型，然后用 MSW 治疗 5 天。以时间依赖性方式测量膝关节周长，并通过 ELISA 检测血清样本中 TNF-α、IL-1β 和 IL-6 蛋白水平。通过 Western blot 检测软骨组织和 C28/I2 细胞中 MMP-3、TIMP-3、STAT3 和 p-STAT3 的蛋白表达，通过甲苯胺蓝染色测定原代软骨细胞和软骨组织中糖胺聚糖的水平。此外，在体外使用 AG490 和 IL-6 来探讨 IL-6/STAT3 通路在 MSU 保护作用中的功能。
MSW 降低了痛风性关节炎模型中的关节肿胀率，并抑制了 MSU 诱导的血清和滑液中 IL-1β、TNF-α 和 IL-6 蛋白水平的上调。IL-1β 诱导 C28/I2 细胞中 p-STAT3 和 MMP-3 蛋白表达增加，TIMP-3 蛋白表达减少。MSW 血清抑制了体外 IL-1β诱导的蛋白表达变化。此外，抑制 STAT3 信号通路否定了 MSW 血清对 C28/I2 细胞中 p-STAT3、MMP-3 和 TIMP-3 蛋白水平的影响。MSW 还显著增加了体内和体外的糖胺聚糖含量。
我们的数据表明，MSW 保护大鼠免受 MSU 诱导的实验性痛风性关节炎，IL-1β/IL-6/STAT3 通路在 MSU 对 GA 的保护作用中起重要作用。
