Purpose: This study aimed to reveal Danggui Buxue Decoction (DBD) candidate targets and mechanisms in the treatment of metastatic colon cancer (MCC), using network pharmacology-based analyses and experimental validation.
Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database query and text mining were used to screen active compounds in DBD, and the Swiss target prediction platform was applied to predict compound-related target proteins. Targets likely associated with MCC were determined using GeneCards and OMIM databases. Targets common to DBD and MCC were obtained from the Venn platform; subsequently, Cytoscape was used to construct drug-compound-target-disease and protein-protein interaction networks. The hub gene was determined by R, while GO and KEGG enrichment analyses were performed on common targets to elucidate biological processes and signaling pathways involved in DBD against MCC. Finally, the metastatic colon cancer mouse model was used to detect the levels of expression of protein Bax, Bcl2, Caspase3, and Cleaved caspase3 by Western blot.
Results: A total of 28 active compounds and 61 common targets were predicted. The main compounds were quercetin, hederagenin, jaranol, methylnissolin, formononetin, calycosin, kaempferol, 3.9-di-O-methylnissolin, 24-propylcholesterol, and 7-O-methylisomucronulatol, present in Astragalus membranaceus (Huangqi, HQ). In addition, beta-sitosterol, ferulic acid, and stigmasterol, present in Angelica sinensis (Danggui, DG), were detected. JUN, PTSG2, EGFR, ESR1and, CASP3 genes were the top 5 hub genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vivo experiment revealed that DBD inhibited MCC by up-regulating the expression of Bax, Caspase3, and Cleaved caspase3, and by down-regulating the expression of Bcl2.
Conclusion: This study revealed candidate DBD targets and mechanisms in the treatment of MCC, using network pharmacology-based analyses and experimental validation. The present findings provide a reference for tumor treatment during the perioperative period.

Keywords: Danggui Buxue Decoction, network pharmacology, primary tumor, metastatic tumor, perioperative period


中文翻译：

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当归补血汤治疗转移性结肠癌：网络药理学分析与实验验证

目的：本研究旨在通过基于网络药理学的分析和实验验证，揭示当归补血汤（DBD）治疗转移性结肠癌（MCC）的候选靶点和机制。
方法：采用中药系统药理学（TCMSP）数据库查询和文本挖掘筛选DBD中的活性化合物，并应用瑞士靶点预测平台预测化合物相关的靶点蛋白。使用 GeneCards 和 OMIM 数据库确定可能与 MCC 相关的目标。DBD 和 MCC 共有的目标是从 Venn 平台获得的；随后，Cytoscape 被用于构建药物-化合物-靶标-疾病和蛋白质-蛋白质相互作用网络。hub基因由R确定，而GO和KEGG富集分析对共同靶点进行，以阐明DBD对MCC的生物学过程和信号通路。最后，采用转移性结肠癌小鼠模型，通过Western blot检测蛋白Bax、Bcl2、Caspase3和Cleaved caspase3的表达水平。
结果：共预测了 28 种活性化合物和 61 个常见靶标。主要化合物是槲皮素、常春藤素、茉莉酸、甲基尼索林、芒柄花素、毛蕊花素、山柰酚、3.9-二-O-甲基尼索林、24-丙基胆固醇和7-O-甲基异微核糖醇，存在于黄芪（黄芪，总部）中。此外，检测到当归（当归，DG）中存在的β-谷甾醇、阿魏酸和豆甾醇。JUN、PTSG2、EGFR、ESR1和CASP3基因是PPI网络中前5位的枢纽基因。GO和KEGG富集分析表明细胞凋亡在所涉及的生物学过程和信号通路中起主要作用。此外，体内实验表明，DBD 通过上调 Bax、Caspase3 和 Cleaved caspase3 的表达以及下调 Bcl2 的表达来抑制 MCC。
结论：本研究使用基于网络药理学的分析和实验验证，揭示了 MCC 治疗中的候选 DBD 靶点和机制。本研究结果可为围手术期肿瘤治疗提供参考。

关键词：当归补血汤 网络药理学 原发肿瘤 转移瘤 围手术期