The Chinese herbal medicine, Huzhen Tongfeng Formula (HZTF), derived from traditional Chinese medicine (TCM) practice, has recognized therapeutic benefits for gouty arthritis (GA). HZTF is currently in the late stage of approval process as a new anti-GA drug application. However, the underlying mechanism of HZTF as an antigout medication is unclear. In this study, we combined network pharmacology and experimental validation approaches to elucidate the mechanism of action of HZTF. First, the relative drug-disease target networks were constructed and analyzed for pathway enrichment. Potential pathways were then validated by in vitro and in vivo experiments. We found that 34 compounds from HZTF matched 181 potential drug targets. Topology analysis revealed 77 core targets of HZTF, which were highly related to gout, following screening of KEGG pathway enrichment. Further analysis demonstrated that the arachidonic acid metabolic pathway was the most relevant pathway involved in the mechanism of HZTF. Validation experiments showed that HZTF significantly inhibited the inflammatory cell infiltration into gouty joints, improved the swelling of affected joints, and increased the pain threshold. HZTF significantly reduced the transcription and production of various cytokines and inflammatory mediators in vitro. In particular, cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase were simultaneously downregulated. In conclusion, our study suggests that the antigout mechanism of HZTF is associated with the inhibition of the arachidonic acid pathway, resulting in the suppression of inflammatory cytokines and mediators. These findings extend our understanding of the pharmacological action of HZTF, rationalizing the application HZTF as an effective herbal therapy for GA.

中文翻译：

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中药护真通风方通过抑制花生四烯酸代谢和炎症介质有效减轻痛风性关节炎

源自传统中医 (TCM) 实践的中草药护真通风方 (HZTF) 已被公认为治疗痛风性关节炎 (GA) 的益处。HZTF目前作为一种新的抗GA药物申请处于批准程序的后期阶段。然而，HZTF 作为抗痛风药物的潜在机制尚不清楚。在这项研究中，我们结合网络药理学和实验验证方法来阐明 HZTF 的作用机制。首先，构建了相关的药物-疾病靶点网络并分析了通路富集。然后通过体外和体内验证潜在途径实验。我们发现来自 HZTF 的 34 种化合物匹配了 181 个潜在的药物靶点。KEGG通路富集筛选后，拓扑分析揭示了与痛风高度相关的77个HZTF核心靶点。进一步分析表明，花生四烯酸代谢途径是参与HZTF机制最相关的途径。验证实验表明，HZTF显着抑制了炎性细胞向痛风关节的浸润，改善了受累关节的肿胀，并提高了痛阈。HZTF在体外显着降低各种细胞因子和炎症介质的转录和产生. 特别是，环氧合酶 (COX)-1、COX-2 和 5-脂加氧酶同时下调。总之，我们的研究表明，HZTF 的抗痛风机制与花生四烯酸途径的抑制有关，从而抑制炎症细胞因子和介质。这些发现扩展了我们对 HZTF 药理作用的理解，使 HZTF 作为 GA 的有效草药疗法的应用合理化。