【摘要】 目的：基于网络药理学和分子动力学分析四妙散治疗痛风的有效成分及作用机制。方法：通过生物信息学数据库获取四妙散的有效成分及靶基因信息并通过GeneCards、DrugBank及OMIM数据库获取痛风相关的潜在靶点信息，借助在线Venny网站、微生信平台、STRING数据库、Cytoscape软件等筛选出药物关键成分和关键靶点。随后进行“中药-复方成分-作用靶点”网络及蛋白质-蛋白质互相作用(Protein-Protein Interaction, PPI)网络分析，根据度值筛选出核心靶点，并对其进行基因本体论(GO)功能注释与京都基因与基因组百科全书(KEGG)通路富集分析，最后通过分子对接和分子动力学评估核心成分和靶点的结合情况。结果：筛选口服生物利用度(Oral bioavailability, OB≥30%)与类药性(Drug-likeness, DL≥0.18)，查重并剔除最终获得69个药物有效成分、735个基因靶点和5个核心靶点，即肿瘤坏死因子(TNF)、过氧化物酶体增殖物激活受体γ(PPARG)、转化生长因子beta 1蛋白(TGFβ1)等。GO分析结果包括肽基酪氨酸磷酸化等生物过程，KEGG分析主要富集在磷脂酰肌醇3激酶-蛋白激酶B信号通路等。分子对接结果提示TNF、PPARG等能与黄芩素自发结合，TGFB1和槲皮素形成的复合物与其他四种相比则更为稳定。分子动力学验证了PPARG和黄芩素具有稳定的结合能。结论：四妙散可能通过黄芩素、山奈酚、槲皮素等成分与TNF、PPARG、TGFβ1等核心靶点结合，调控炎症相关通路和生物学过程，发挥治疗痛风的作用，而分子动力学结果表明黄芩素可能具有调控PPARG的潜力，可为PPARG抑制剂的发现提供参考，本研究为四妙散的临床运用与成分优化提供了理论依据。更多还原

【Abstract】 Objective: Based on network pharmacology and molecular dynamics, an analysis was performed the active ingredients and mechanism of action of Si Miao Powder in the treatment of gout. Methods: The bioinformatics database was used to obtain information on the active ingredients and target genes of Si Miao Powder, and the GeneCards, DrugBank and OMIM databases were used to obtain information on the potential targets related to gout. The key components and targets were screened with the help of online Venny website, Wei Sheng Xin website, STRING database and Cytoscape software. Subsequently, we analyzed the network of "Traditional Chinese medicine-compound components-targets" and the network of "Protein-Protein Interaction(PPI)".The core targets were screened according to the degree value and analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Finally, molecular docking and molecular dynamics were utilized to assess the binding of core components and targets. Results:Screening for oral bioavailability(OB≥30 %) and drug-like properties(DL≥0.18), checking and elimination finally yielded 69 drug active ingredients, 735 gene targets and 5 core targets, namely, tumor necrosis factor(TNF),peroxisome proliferator-activated receptor gamma(PPARG), transforming growth factor beta 1 protein(TGFβ1),etc. The results of GO analysis included biological processes such as peptidyl tyrosine phosphorylation, and KEGG analysis was mainly enriched in phosphatidylinositol 3-kinase-protein kinase B signaling pathway and others. The molecular docking results suggested that TNF and PPARG could spontaneously bind to baicalein, while the complex formed by TGFB1 and quercetin was more stable compared with the other four. Molecular dynamics verified that PPARG and baicalein had stable binding energy. Conclusion: Si Miao Powder may play a role in the treatment of gout by binding components such as baicalein, kaempferol, and quercetin to core targets such as TNF, PPARG, and TGFβ1 to modulate inflammation-related pathways and biological processes. Molecular dynamics results indicate that baicalein may have the potential to modulate PPARG, which may provide a reference for the discovery of PPARG inhibitors. This study provides a theoretical basis for the clinical application and formulation optimization of Si Miao Powder.更多还原