Guangdong Key Laboratory for Research and Development of Natural Drugs, The Public Service Platform of South China Sea for R&D Marine Biomedicine Resources, Marine Biomedical Research Institute, Department of Pharmacology, Guangdong Medical University, Zhanjiang, 524023, China; Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, 523808, China.
Institute of Medical Systems Biology, School of Public Health, Guangdong Medical University, Dongguan, 523808, China.
J Ethnopharmacol. 2020 Apr 24;252:112603. doi: 10.1016/j.jep.2020.112603. Epub 2020 Jan 22.
Traditional Chinese medicine (TCM) holds a great promise for preventing complex chronic diseases through a holistic way. Certain Chinese medicine formulae from TCM are effective for treating and preventing cancer in clinical practice. Xiaoai Jiedu Recipe (XJR) is a Chinese medicine formula that has been used to treat breast cancer (BC). However, its active ingredients and therapeutic mechanisms on tumor are unclear. Therefore, further investigation is necessary.
This study aims to elucidate the active compounds of XJR and its molecular mechanisms for the treatment of BC.
A comprehensive approach was used to clarify the pharmacodynamic basis of XJR and its pharmacological mechanism, including the acquisition of differentially expressed genes of BC, screening of active ingredients and their targets, construction of complex internetwork between drugs and diseases, and analysis of the key subnetwork. Finally, these results were validated by in vitro experiments and comparison with literature reviews.
By using bioinformatics, 5211 differentially expressed genes of BC were identified, more than half of them had been reported in previous studies. By using network analysis, 113 potential bioactive compounds in the ten component herbs of XJR and 157 BC-related targets were identified, which were significantly enriched in 85 pathways and 1321 GO terms. The in vitro studies showed that quercetin and ursolic acid, the active components of XJR, could effectively inhibit the proliferation of breast cancer cells, and the combination of the two components could significantly decrease the mitochondrial membrane potential and suppress the activation of PI3K-Akt signaling pathway, thus inducing apoptosis of cancer cells.
XJR played an important role in anti-BC through multi-component, multi-target and multi-pathway mechanisms, in which quercetin and ursolic acid may be the key active components. The anticancer effect of multi-component application was better than that of a single component. This study not only deepened our understanding of the role of TCM in the prevention and treatment of diseases, but also provided a reference for the in-depth research, development and application of the ancient medicine.
中医（TCM）通过整体方法为预防复杂的慢性疾病提供了巨大的希望。某些中药方剂在临床实践中对治疗和预防癌症有效。消癌解毒方（XJR）是一种用于治疗乳腺癌（BC）的中药方剂。然而，其对肿瘤的活性成分和治疗机制尚不清楚。因此，有必要进一步研究。
本研究旨在阐明 XJR 的活性成分及其治疗 BC 的分子机制。
采用综合方法阐明 XJR 的药效学基础及其药理机制，包括获得 BC 的差异表达基因，筛选活性成分及其靶点，构建药物与疾病之间的复杂互联网，以及分析关键子网。最后，通过体外实验和与文献综述的比较对这些结果进行了验证。
通过使用生物信息学，鉴定出 5211 个 BC 的差异表达基因，其中一半以上在以前的研究中已有报道。通过网络分析，从 XJR 的十种成分草药中鉴定出 113 种潜在的生物活性化合物和 157 个 BC 相关靶点，这些靶点在 85 条途径和 1321 个 GO 术语中显著富集。体外研究表明，XJR 的活性成分槲皮素和熊果酸可有效抑制乳腺癌细胞的增殖，两种成分的组合可显著降低线粒体膜电位并抑制 PI3K-Akt 信号通路的激活，从而诱导癌细胞凋亡。
XJR 通过多成分、多靶点和多途径机制在抗 BC 中发挥重要作用，其中槲皮素和熊果酸可能是关键的活性成分。多成分应用的抗癌效果优于单一成分。本研究不仅加深了我们对中医在疾病预防和治疗中的作用的理解，也为古代医学的深入研究、开发和应用提供了参考。
