Department of Cardiovascular Disease, Hebei Province Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou, China.
Department of Cardiovascular Disease, Hebei Province Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou, China. Email:
Ann Palliat Med. 2021 Jan;10(1):16-28. doi: 10.21037/apm-20-2204. Epub 2021 Jan 18.
Cancer patients who receive anthracycline-based chemotherapy regimens often discontinue chemotherapy due to cardiotoxicity. Preventing and reducing anthracycline-induced cardiotoxicity (ACT) is a hot topic in cardio-oncology research. Network pharmacology is a new discipline that integrates pharmacology, bioinformatics, and systems biology. It can be used to analyze the mechanism of action of drugs in the body from a holistic perspective by constructing a "disease-gene-drug" network, providing a new method to explore compounding mechanisms of Chinese medicine. Based on network pharmacology, this study explored the mechanism of the reduction of cardiotoxicity of anthracyclines by Qishen Huanwu Capsule.
The active ingredients of Qishen Huanwu Capsule and their targets were screened based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Chemistry Database. The target genes of ACT were screened through the PharmGkb, GeneCards, Online Mendelian Inheritance in Man (OMIM), Genetic Association Database (GAD), and Therapeutic Target Database (TTD). The Venny2.1 online analysis tool was used to construct a Venn diagram to obtain the common targets of ACT and Qishen Huanwu Capsule. The STRING platform was used to construct the protein-protein interactions (PPI) among the common targets; ClueGO software was used to perform Gene Ontology (GO) biological process enrichment analysis for the common targets; the R language was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; and the results were visualized using Cytoscape software.
The predictions indicate that Qishen Huanwu Capsule has 35 main active ingredients capable of reducing the cardiotoxicity of anthracyclines and that there are 36 common targets of ACT and Qishen Huanwu Capsule that are enriched in 133 biological processes and 27 signaling pathways.
Qishen Huanwu Capsule regulates phosphatidylinositol 3‑kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), forkhead box class O (FoxO) and other signaling pathways by regulating targets such as RAC-alpha serine/threonine protein kinase (Akt1), mitogen-activated protein kinase 1 (MAPK1), and mitogen-activated protein kinase 8 (MAPK8) and thereby inhibits oxidative stress and regulates apoptosis and autophagy to reduce the cardiotoxicity of anthracyclines.
接受蒽环类化疗方案的癌症患者常因心脏毒性而停止化疗。预防和减少蒽环类药物引起的心脏毒性（ACT）是心脏肿瘤学研究的热点。网络药理学是一门整合药理学、生物信息学和系统生物学的新兴学科。它可以通过构建“疾病-基因-药物”网络，从整体角度分析药物在体内的作用机制，为探索中药的复方机制提供一种新方法。基于网络药理学，本研究探讨了芪参活五胶囊减轻蒽环类药物心脏毒性的作用机制。
基于中药系统药理学数据库与分析平台和化学数据库筛选芪参活五胶囊的活性成分及其靶点；通过 PharmGkb、GeneCards、在线孟德尔遗传数据库（OMIM）、遗传关联数据库（GAD）和治疗靶点数据库（TTD）筛选 ACT 的靶基因；使用 Venny2.1 在线分析工具构建 Venn 图，获得 ACT 和芪参活五胶囊的共同靶点；使用 STRING 平台构建共同靶点的蛋白质-蛋白质相互作用（PPI）网络；使用 ClueGO 软件对共同靶点进行基因本体（GO）生物过程富集分析；使用 R 语言进行京都基因与基因组百科全书（KEGG）通路富集分析；使用 Cytoscape 软件可视化结果。
预测表明，芪参活五胶囊有 35 种主要活性成分，可降低蒽环类药物的心脏毒性，ACT 和芪参活五胶囊有 36 个共同靶点，富集于 133 个生物过程和 27 个信号通路。
芪参活五胶囊通过调节 Akt1、MAPK1、MAPK8 等靶点，调节磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）、丝裂原激活蛋白激酶（MAPK）、叉头框蛋白 O（FoxO）等信号通路，抑制氧化应激，调节细胞凋亡和自噬，从而减轻蒽环类药物的心脏毒性。
