Molecular Mechanism of Senecio scandens Buch.-Ham. in Regulating Hepatic Carcinoma Based on Bioinformatics and Network Pharmacology
Keywords:
Hepatic carcinoma, Senecio scandens Buch.-Ham., Bioinformatics, Network pharmacology, Molecular mechanismAbstract
Objective: To investigate the molecular mechanism of Senecio scandens Buch.-Ham. in regulating hepatocellular carcinoma through bioinformatics and network pharmacology techniques and methodologies. Methods: The active components and targets of Senecio scandens Buch.-Ham. were identified using the systematic pharmacology database and analysis platform for traditional Chinese medicine, the traditional Chinese medicine database of Taiwan region, and the bioinformatics database for molecular mechanisms of traditional Chinese medicine. Datasets GSE57957, GSE60502, and GSE84402 were downloaded from public gene expression databases, and differentially expressed genes (DEGs) were analyzed using the GEO2R online tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed using the DAVID database. Protein interactions and the “active component-target-disease” network were constructed using the STRING database and Cytoscape 3.7 software to identify key genes. Expression differences and prognosis were analyzed using the GEPIA database. AutoDock 4.6 software was utilized for the docking verification of candidate targets. Results: A total of eight active components, including 2-furancarboxylic acid, 6-hydroxy-2-(2-phenylethyl)chromone, chrysanthemaxanthin, chrysanthemic acid, flavoxanthin, hydroquinone, p-hydroxyacetophenone, and seneciphylline, were identified with 321 targets. The three datasets (GSE57957, GSE60502, and GSE84402) revealed 245 common DEGs. In the “active component-target-disease” network, six components were involved in regulating hepatic carcinoma, with 17 common targets. GO biological processes involved ethanol oxidation, redox reactions, the cyclooxygenase P450 pathway, and fatty acid long-chain metabolism. KEGG pathways involved the fatty acid degradation pathway, chemical carcinogenesis pathway, metabolic pathway, retinol pathway, and cytochrome P450 metabolism pathway. Key targets in the protein-protein interaction network were CYP1A1, PTGS2, ESR1, and NQO1. ESR1 and NQO1 showed significant differences and were associated with poor prognosis. Molecular docking verification indicated a close binding of NQO1 to the active ingredient. Conclusion: Senecio scandens Buch.-Ham. may exert an auxiliary anti-hepatocellular carcinoma effect by regulating metabolic pathways in hepatocellular carcinoma cells.
References
Siegel RL, Miller KD, Fuchs HE, et al., 2021, Cancer Statistics, 2021. CA Cancer J Clin, 71(1): 7–33.
Guo Y, Wu Y, Zhang Z, et al., 2021, Exploring the Medication Rules of Primary Liver Cancer Based on Literature Mining. World Science and Technology - Modernization of Traditional Chinese Medicine, 23(4): 1165–1170.
Xu D, Zhou X, Gao H, et al., 2014, Research Progress on Chemical Constituents and Pharmacological Effects of Senecio scandens. Chinese Pharmacist, 17(9): 1562–1565.
Ali SI, Gopalakrishnan B, Venkatesalu V, 2018, Evaluation of Larvicidal Activity of Senecio laetus Edgew. Against the Malaria Vector, Anopheles stephensi, Dengue Vector, Aedes aegypti, and Bancroftian filariasis Vector, Culex quinquefasciatus. S Afr J Bot, (114): 117–125.
Yao G, Liang TQ, Zhang H, et al., 2020, The Influence of Ethanol Extraction of Senecio scandens Collected in Guizhou on the Viscera Quality and Organ Coefficient. J Guizhou Univ Tradit Chin Med, (42): 29–33.
Jiang KY, Ye XL, Xiong F, et al., 2021, The Protective Effects and Mechanism of Alismatis Rhizoma Extracts Against Senecionine-Induced Acute Liver Injury in Mice. Acta Pharm Sin, (2): 1–13.
Zhou X, 2011, Study on the Relationship Between Metabolic Enzyme Gene Polymorphism, External Exposure Factors, and Their Interaction and Liver Cancer Susceptibility, dissertation, Guangxi Medical University.
Zheng Z, 2008, Study on the Correlation Between CYP1A1 Gene Polymorphism and the Occurrence of Primary Liver Cancer, dissertation, Guangxi Medical University.
Zheng Y, Comaills V, Burr R, et al., 2019, COX-2 Mediates Tumor Stromal Protein Signaling to Initiate Tumorigenesis. Proc Natl Acad Sci USA, 116(12): 5223–5232.
Enomoto A, Itoh K, Nagayoshi E, et al., 2001, High Sensitivity of Nrf2 Knockout Mice to Acetaminophen Hepatotoxicity Associated with Decreased Expression of ARE-Regulated Drug Metabolizing Enzymes and Antioxidant Genes. Toxicol Sci, 1(1): 169–177.