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BACKGROUND

The incidence of gout has been rapidly increasing in recent years with the changing of diet. At present, modern medications used in the clinical treatment of gout showed several side effects, such as gastrointestinal damage and the increased risk of cardiovascular disease. The traditional Chinese prescription Simiao Powder (SMP) has a long history in the treatment of acute gouty arthritis (AGA) and has a good curative effect. However, the mechanism and target of its therapeutic effects are still not completely understood.

METHODS

Potential active compounds (PACs) and targets of SMP were found in the TCMSP database, and the disease target genes related to AGA were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, TTD, OMIM, and PharmGKB disease databases with "acute gouty arthritis" and "Arthritis, Gouty" as keywords, respectively. The network of "Traditional Chinese medicine (TCM)-PACs-potential targets of acute gouty arthritis" was constructed with the Cytoscape 3.7.2 software, and the target genes of acute gouty arthritis were intersected with genes regulated by active compounds of SMP. The resultant common gene targets were input into Cytoscape 3.7.2 software, and the BisoGenet plug-in was used to construct a PPI network. The GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersecting target proteins were performed using R software and corresponding program packages. The molecular docking verification was carried out between the potentially active compounds of SMP and the core target at the same time.

RESULTS

40 active components and 203 targets were identified, of which 95 targets were common targets for the drugs and diseases. GO function enrichment analysis revealed that SMP regulated several biological processes, such as response to lipopolysaccharide and oxidative stress, RNA polymerase II transcription regulator complex, protein kinase complex, and other cellular and molecular processes, including DNA-binding transcription factor binding. Results of KEGG pathway analysis showed that SMP was associated with AGA-related pathways such as interleukin-17 (IL-17), tumor necrosis factor (TNF), p53, and hypoxia-inducible factor 1 (HIF-1) signaling pathways. The results of molecular docking showed that active compounds in SMP exhibited strong binding to five core protein receptors (TP53, FN1, ESR1, CDK2, and HSPA5).

CONCLUSIONS

Active components of SMP, such as quercetin, kaempferol, wogonin, baicalein, beta-sitosterol, and rutaecarpine, showed therapeutic effects on AGA. These compounds were strongly associated with core target proteins (such as TP53, FN1, ESR1, CDK2, and HSPA5). This study reveals that IL-17, TNF, p53, and HIF-1 signaling pathways mediate the therapeutic effects of SMP on AGA. These findings expand our understanding of the mechanism of SMP in the treatment of AGA.

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

背景

近年来，随着饮食结构的改变，痛风的发病率迅速上升。目前，用于痛风临床治疗的现代药物显示出多种副作用，如胃肠道损伤和心血管疾病风险增加。传统中药方剂四妙散（SMP）在治疗急性痛风性关节炎（AGA）方面历史悠久，疗效良好。然而，其治疗作用的机制和靶点仍未完全明确。

方法

在中药系统药理学数据库与分析平台（TCMSP）中查找SMP的潜在活性成分（PACs）和靶点，并分别以“急性痛风性关节炎”和“痛风性关节炎”为关键词，通过搜索CTD、DisGeNET、DrugBank、GeneCards、TTD、OMIM和PharmGKB疾病数据库获取与AGA相关的疾病靶基因。使用Cytoscape 3.7.2软件构建“中药 - PACs - 急性痛风性关节炎潜在靶点”网络，并将急性痛风性关节炎的靶基因与SMP活性成分调控的基因进行交集分析。将得到的共同基因靶点输入Cytoscape 3.7.2软件，使用BisoGenet插件构建蛋白质 - 蛋白质相互作用（PPI）网络。使用R软件及相应程序包对交集靶蛋白进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析。同时对SMP的潜在活性成分与核心靶点进行分子对接验证。

结果

鉴定出40种活性成分和203个靶点，其中95个靶点是药物与疾病的共同靶点。GO功能富集分析显示，SMP调节多种生物学过程，如对脂多糖和氧化应激的反应、RNA聚合酶II转录调节复合物、蛋白激酶复合物以及其他细胞和分子过程，包括DNA结合转录因子结合。KEGG通路分析结果表明，SMP与AGA相关通路如白细胞介素 - 17（IL - 17）、肿瘤坏死因子（TNF）、p53和缺氧诱导因子1（HIF - 1）信号通路相关。分子对接结果显示，SMP中的活性成分与五个核心蛋白受体（TP53、FN1、ESR1、CDK2和HSPA5）表现出强烈结合。

结论

SMP的活性成分，如槲皮素、山柰酚、汉黄芩素、黄芩苷、β - 谷甾醇和吴茱萸次碱，对AGA具有治疗作用。这些化合物与核心靶蛋白（如TP53、FN1、ESR1、CDK2和HSPA5）密切相关。本研究揭示IL - 17、TNF、p53和HIF - 1信号通路介导SMP对AGA的治疗作用。这些发现扩展了我们对SMP治疗AGA机制的理解。