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    基于网络药理学和实验验证的大承气汤改善功能性便秘的作用机制研究

    Mechanisms of Dachengqi Decoction in improving functional constipation based on network pharmacology and experimental validation

    • 摘要: 目的 探讨大承气汤治疗功能性便秘的物质基础及潜在分子机制。方法 运用网络药理学方法,利用TCMSP数据库筛选大承气汤中活性成分及其对应靶点基因。通过GeneCards等数据库检索功能性便秘相关靶点,构建"药物-疾病"相互作用网络,筛选核心靶点,并进行GO 功能富集和KEGG 通路富集分析。进一步构建"药物-有效成分-靶点-通路"网络,并对关键活性成分与潜在核心靶点进行分子对接。通过体外酶活性实验和动物实验验证大承气汤对关键靶点和相关通路分子表达的调控作用。结果 大承气汤治疗功能性便秘的核心成分包括芹菜素、木犀草素等,主要靶点包括环氧化酶(COX)-1、COX-2等。动物实验结果表明,大承气汤可显著降低功能性便秘模型大鼠血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β含量,并抑制IL-17信号通路中炎症因子mRNA的表达水平。结论 大承气汤可能通过多成分、多靶点、多通路协同作用,发挥抗炎效应,从而缓解功能性便秘症状。其作用机制可能与抑制IL-17信号通路、减轻肠道局部炎症密切相关。

       

      Abstract: Objective To explore the material basis and potential molecular mechanisms of Dachengqi Decoction in the treatment of functional constipation. Methods Using network pharmacology, the active ingredients of Dachengqi Decoction and their corresponding target genes were screened from the TCMSP database. Functional constipation-related targets were retrieved from databases such as GeneCards to construct a "drug-disease" interaction network, identify core targets, and perform Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Additionally, a "drug-effective component-target-pathway" network was constructed, and molecular docking was performed on key active ingredients and potential core targets. The regulation of key targets and signaling molecules in relevant pathways was further validated by in vitro enzyme activity assays and animal experiments. Results The core components of Dachengqi Decoction for treating functional constipation include luteolin and apigenin, with major targets including COX-1 and COX-2. Animal experiments demonstrated that Dachenqi Decoction significantly reduced the levels of TNF-α and IL-1β in the serum of functional constipation model rats, and inhibited the mRNA expression of inflammatory factors in the IL-17 signaling pathway. Conclusions Dachengqi Decoction may exert its anti-inflammatory effects through a multi-component, multi-target, and multi-pathway collaborative action, thereby alleviating the symptoms of functional constipation. Its mechanisms are likely related to the inhibition of the IL-17 signaling pathway and the reduction of local intestinal inflammation.

       

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