Abstract:
Background: Wuwei Xiaodu Drink (WWXDD), a classical decoction of traditional Chinese medicine, has been clinically used for the treatment of gout in China for many years. This study aimed to demonstrate the efficacy of WWXDD in treating gout flares and elucidate its underlying therapeutic mechanism. Methods: A randomized control trial was conducted to compare the effectiveness of WWXDD with low-dose colchicine in gout arthritis. The primary outcome was the clinical response rate on the 7th day, and joint syndrome score and serological tests were secondary outcome measures and were compared in the two groups on the 1st and 7th day. Then we used a network pharmacology approach to investigate the possible mechanism of WWXDD in treating gout, and the effects of WWXDD on the MSU-induced rat model were observed. Results: In the clinical trial, a total of 78 participants completed the study, and the results demonstrated comparable clinical complete response rates, joint symptom scores, and serological test outcomes between the two groups on the 7th day. Network pharmacology analysis identified 51 core genes that target gout and WWXDD interactions. Notably, strong significant correlations were observed with inflammation cytokine genes and metabolism-related genes. Furthermore, it was found that WWXDD reduced gene expression levels of inflammation cytokines including IL-1β, TNF, and IL-18 in an MSU-induced rat model while increasing IL-10 expression. Additionally, WWXDD decreased insulin gene expression in this model. Moreover, WWXDD exhibited a reduction in both gene and protein expressions associated with the NLRP3-mediated inflammatory pathway in inflamed joints of rats. Conclusion: The results of the present study suggested the anti-inflammatory effects of WWXDD in the treatment of gouty arthritis, partially through inhibiting NLRP3 inflammasome activation. Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2100047807.
摘要:
背景:武威小都饮料(WWXDD),中药的经典汤剂,在中国已经在临床上用于治疗痛风多年。本研究旨在证明WWXDD治疗痛风发作的疗效,并阐明其潜在的治疗机制。方法:采用随机对照试验,比较WWXDD与小剂量秋水仙碱治疗痛风性关节炎的疗效。主要结果是第7天的临床反应率,关节综合征评分和血清学检查是次要结局指标,并在第1天和第7天比较两组。然后我们使用网络药理学方法来研究WWXDD治疗痛风的可能机制。观察WWXDD对MSU诱导大鼠模型的影响。结果:在临床试验中,共有78名参与者完成了这项研究,结果表明,临床完全缓解率相当,关节症状评分,和第7天两组之间的血清学测试结果。网络药理学分析确定了51个靶向痛风和WWXDD相互作用的核心基因。值得注意的是,观察到与炎症细胞因子基因和代谢相关基因的显著相关性。此外,研究发现,WWXDD降低了炎症细胞因子包括IL-1β的基因表达水平,TNF,和IL-18在MSU诱导的大鼠模型中,同时增加IL-10的表达。此外,WWXDD降低了该模型中的胰岛素基因表达。此外,WWXDD在大鼠发炎的关节中表现出与NLRP3介导的炎症途径相关的基因和蛋白质表达的降低。结论:本研究结果提示WWXDD治疗痛风性关节炎具有抗炎作用,部分通过抑制NLRP3炎性体激活。临床试验注册:ClinicalTrials.gov,标识符ChiCTR2100047807。