College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
College of Traditional Chinese Medicine, Research and Innovation Team of Emotional Diseases and Syndrome Research, Shandong University of Traditional Chinese Medicine, Jinan, China.
Chem Biol Drug Des. 2024 Aug;104(2):e14604. doi: 10.1111/cbdd.14604.
This study aimed to investigate the mechanism of action of myrrh in breast cancer (BC) treatment and identify its effective constituents. Data on the compounds and targets of myrrh were collected from the TCMSP, PubChem, and Swiss Target Prediction databases. BC-related targets were obtained from the Genecard database. A protein-protein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted on the intersecting targets of the disease and drug. The key targets of myrrh in BC treatment were identified based on the PPI network. The active constituents of myrrh were determined through reverse-screening using the top 20 KEGG pathways. Macromolecular docking studies, molecular dynamic (MD) simulations, and cell assays were utilized to validate the active constituents and critical targets. Network pharmacology indicated that VEGFA, TP53, ESR1, EGFR, and AKT1 are key targets of myrrh. Pelargonidin chloride, Quercetin, and Naringenin were identified as the active constituents of myrrh. Macromolecular docking showed that Quercetin and Naringenin have strong docking capabilities with ESR1. The results of MD simulation experiments align with those of molecular docking experiments. Cell and western blot assays demonstrated that Quercetin and Naringenin could inhibit MCF-7 cells and significantly reduce the expression of ESR1 protein. The findings reveal the active constituents, key targets, and molecular mechanisms of myrrh in BC treatment, providing scientific evidence that supports the role of myrrh in BC therapy. Furthermore, the results suggest that network pharmacology predictions require experimental validation for reliability.
本研究旨在探讨没药在乳腺癌（BC）治疗中的作用机制，并鉴定其有效成分。从 TCMSP、PubChem 和 Swiss Target Prediction 数据库中收集了没药的化合物和靶标数据。从 Genecard 数据库中获得了与 BC 相关的靶标。对疾病和药物的交集靶标进行了蛋白质-蛋白质相互作用（PPI）分析、基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）分析。根据 PPI 网络确定了没药治疗 BC 的关键靶标。通过对前 20 个 KEGG 途径的反向筛选确定了没药的活性成分。利用大分子对接研究、分子动力学（MD）模拟和细胞实验验证了活性成分和关键靶标。网络药理学表明，VEGFA、TP53、ESR1、EGFR 和 AKT1 是没药的关键靶标。鉴定出氯化锦葵色素、槲皮素和柚皮苷为没药的活性成分。大分子对接表明，槲皮素和柚皮苷与 ESR1 具有很强的结合能力。MD 模拟实验的结果与分子对接实验的结果一致。细胞和 Western blot 实验表明，槲皮素和柚皮苷能够抑制 MCF-7 细胞，并显著降低 ESR1 蛋白的表达。研究结果揭示了没药在 BC 治疗中的活性成分、关键靶标和分子机制，为没药在 BC 治疗中的作用提供了科学依据。此外，结果表明，网络药理学预测需要实验验证以确保其可靠性。
