Prediction of the mechanisms of Xiaoai Jiedu Recipe in the treatment of breast cancer: A comprehensive approach study with experimental validation. (24th April 2020)

• Record Type: Journal Article
• Authors: Li, Yuyun; Li, Rang; Zeng, Zhanwei; Li, Siyan; Luo, Shiying; Wu, Jiahuan; Zhou, Chenhui; Xu, Daohua
• Is Part Of: Journal of ethnopharmacology. Volume 252(2020)
• Publication Date: 2020-04-24
• Subjects: Traditional Chinese medicine -- Xiaoai Jiedu Recipe -- Network pharmacology -- Bioinformatics -- Quercetin -- Ursolic acid; BC breast cancer -- CCK-8 Cell Counting Kit-8 -- GO Gene Ontology -- KEGG Kyoto Encyclopedia of Genes and Genome -- MMP mitochondrial membrane potential -- OD optical density -- TCM traditional Chinese medicine -- XJR Xiaoai Jiedu Recipe; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.112603
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: 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. Aim of the study: This study aims to elucidate the active compounds of XJR and its molecular mechanisms for the treatment of BC. Materials and methods: 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. Results: 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. Conclusions: 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. Graphical abstract: Image 1