Combination of UPLC–Q-TOF/MS and Network Pharmacology to Reveal the Mechanism of Qizhen Decoction in the Treatment of Colon Cancer

Abstract

Traditional Chinese medicine (TCM) has been utilized for the treatment of colon cancer. Qizhen decoction (QZD), a potential compound prescription of TCM, possesses multiple biological activities. It has been proven clinically effective in the treatment of colon cancer. However, the molecular mechanism of anticolon cancer activity is still not clear. This study aimed to identify the chemical composition of QZD. Furthermore, a collaborative analysis strategy of network pharmacology and cell biology was used to further explore the critical signaling pathway of QZD anticancer activity. First, ultraperformance liquid chromatography–quadrupole time-of-flight/mass spectrometry (UPLC–Q-TOF/MS) was performed to identify the chemical composition of QZD. Then, the chemical composition database of QZD was constructed based on a systematic literature search and review of chemical constituents. Moreover, the common and indirect targets of chemical components of QZD and colon cancer were searched by multiple databases. A protein–protein interaction (PPI) network was constructed using the String database (). All of the targets were analyzed by Gene Oncology (GO) bioanalysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the visual network topology diagram of “Prescription–TCM–Chemical composition–Direct target–Indirect target–Pathway” was constructed by Cytoscape software (v3.7.1). The top molecular pathway ranked by statistical significance was further verified by molecular biology methods. The results of UPLC–Q-TOF/MS showed that QZD had 111 kinds of chemical components, of which 103 were unique components and 8 were common components. Ten pivotal targets of QZD in the treatment of colon cancer were screened by the PPI network. Targets of QZD involve many biological processes, such as the signaling pathway, immune system, gene expression, and so on. QZD may interfere with biological pathways such as cell replication, oxygen-containing compounds, or organic matter by protein binding, regulation of signal receptors or enzyme binding, and affect cytoplasm and membrane-bound organelles. The main antitumor core pathways were the apoptosis metabolic pathway, the PI3K–Akt signal pathway, and so on. Expression of the PI3K–Akt signal pathway was significantly downregulated after the intervention of QZD, which was closely related to the inhibition of proliferation and migration of colon cancer cells by cell biology methods. The present work may facilitate a better understanding of the effective components, therapeutic targets, biological processes, and signaling pathways of QZD in the treatment of colon cancer and provide useful information about the utilization of QZD.

Rapid and comprehensive identification of chemical constituents in Mai-Luo-Shu-Tong pill by UHPLC-Q-Orbitrap HRMS combined with a data mining strategy

“…As a result, a total of 145 compounds (other than the known compounds in Section 3.1) including 43 flavonoids, 40 terpenes, 24 phenylpropanoids and 38 others were identified by comparison with accurate molecular formula, retention times, MS fragmentation ions, characteristic neutral losses, the cleavage regularity of standards and literature data. 15,16,21–33 Among them, 4 triterpenes were potentially new compounds, which were never found in Scifinder (Chemical Abstract Service, America). The structures of the identified compounds and their MS data are listed in Fig.…”

“…15,17 Taking glycyrrhizic acid as In addition, ten compounds including skimmetin (14), isocorypalmine (30), scopoletol (44), magnoorine (77), aucubin (132), senkyunolide (136), skimmianin (140), butylidenephthalide (157), butylphthalide (187) and ligustilide (196) were identied combining with reference standards and literature data. 15,16,[21][22][23][24][25][26][27][28] These compounds contained structures such as alkaloids, lactones, etc. and the specic characteristic fragments and identications can be referred to Table S1.…”

Multi-omics analyses of CD276 in pan-cancer reveals its clinical prognostic value in glioblastoma and other major cancer types

“…Given this background,we explored the subcellular localization of CD276 and its localization in different cancer cell lines. Furthermore, the GPS-Prot ( http://gpsprot.org/ ) [ 29 ], GeneMANIA ( http://genemania.org/ ) [ 30 ] and STRING ( https://string-db.org/ ) [ 31 ] databases were utilized to establish the protein–protein interaction network (PPI) of CD276 . Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of CD276 co-expressed genes were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) ( https://david.ncifcrf.gov/ ) [ 32 ].…”

A novel method for investigating the mechanism of the anti‐rheumatoid arthritis activity of Angelicae pubescentis radix by integrating UHPLC–QTOF/MS and network pharmacology

“…Network pharmacology, mainly based on existing data in the database to establish the “compound–target–disease” model, may help investigators analyze the impact of drugs on the entire disease network and predict the effects of pharmacodynamic components on certain key targets and their pathways. This technology has been proven to be useful in exploring the mechanisms of active compounds present in Flos Chrysanthemi Indici (Tian et al, 2020), Qizhen Decoction (Kong et al, 2021), Platycodon grandiflorum (Deng et al, 2020), Xiaoyaosan (Liu, Wei, et al, 2021), Jinzhen oral liquid (Guo et al, 2019) and Eucommia ulmoides Oliver (Huang et al, 2021).…”