Objective: This study employed computational pharmacology to explore the possible therapeutic targets and molecular mechanisms of F1012-2, a novel sesquiterpene lactone from Eupatorium lindleyanum DC. (EL), against viral pneumonia. Methods: With network pharmacology, we first looked into various databases for genes and proteins related to viral pneumonia, as well as the potential targets of F1012-2. By overlapping these 2 groups of genes, we acquired the candidate targets of F1012-2 against viral pneumonia. Afterward, enrichment analysis was performed to elucidate the interactive targets in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. The protein–protein interaction (PPI) network was constructed through the STRING database, and the results were imported into Cytoscape software to search for the key genes by Network Analyzer. Finally, molecular docking analysis was used to further validate the candidate targets of F1012-2 against viral pneumonia. Results: A total of 110 target genes were found for the 3 compounds within F1012-2 (Eupalinolide G, [EG] Eupalinolide I, [EI] and Eupalinolide J [EJ]), while 4322 potential therapeutic targets were uncovered related to viral pneumonia, and the intersection of the 2 groups generated 78 target genes. Among the candidate genes, epidermal growth factor receptor (EGFR), interleukin-1beta (IL1B), tyrosine-protein kinase SRC, Caspase-3 (CASP3), and transcription factor and oncoprotein JUN have the highest degree, betweenness, and closeness, which could fit into binding with EG, EI, and EJ. The enrichment analysis indicated that the major pathways involved were sphingolipid, neurotrophin, tumor necrosis factor (TNF), and Toll-like receptor signaling pathways. Conclusion: These findings showed that by the combination of network pharmacology and molecular docking, we could speculate on the possible mechanism of F1012-2's effect on viral pneumonia, with EGFR, IL1B, SRC, and CASP3 as the promising targets.
F1012-2, a novel sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum DC, exhibits an antitumor effect. In this study, we investigated the anticancer activities of F1012-2 on ten human breast cancer lines and demonstrated significantly lower IC50 values for triple-negative breast cancer (TNBC) than for non-TNBC cell lines. The transcription factors p53 and nuclear factor-?B (NF-?B) are important regulators of tumorigenesis. F1012-2 not only depleted mutant p53, but also activated wild-type p53. F1012-2 reduced the expression of phosphorylated p65 and p105 F-?B family members and coregulated p53, NF-?B members and their dependent targets. To further clarify the key role of p53, lentivirus small hairpin RNA (shRNA) infection was used to knockdown p53 in MDAMB- 231 cells. F1012-2 significantly reduced the inhibitory effect on cell proliferation and apoptosis, while the levels of p53, NF-?B family members and their dependent genes were not significantly different. F1012-2 exhibited a significant antitumor effect and reduced the expression of p53 in MDA-MB-231 xenografts. Taken together, our results show that F1012-2 exhibited an inhibitory effect on TNBC and affected the regulation of p53/NF-?B signaling pathways.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.