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Volume 28, Issue 3
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402
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Abstract

Background

Esophageal cancer (EC) is one of the deadliest malignancies worldwide. Gynostemma pentaphyllum Thunb. Makino (GpM) has been used in traditional Chinese medicine as a treatment for tumors and hyperlipidemia. Nevertheless, the active components and underlying mechanisms of anti-EC effects of GpM remain elusive.

Objective

This study aims to determine the major active ingredients of GpM in the treatment of EC and to explore their molecular mechanisms by using network pharmacology, molecular docking, and experiments.

Methods

Firstly, active ingredients and potential targets of GpM, as well as targets of EC, were screened in relevant databases to construct a compound-target network and a protein-protein interaction (PPI) network that narrowed down the pool of ingredients and targets. This was followed by gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, molecular docking, ADME and toxicity risk prediction, cell viability assays, scratch assays, Transwell cell invasion assays, and Western blotting analysis were subsequently applied to validate the results of the network analysis.

Results

The screening produced a total of 21 active ingredients and 167 ingredient-related targets for GpM, along with 2653 targets for EC. The PPI network analysis highlighted three targets of interest, namely AKT1, TP53, and VEGFA, and the compound-target network identified three possible active ingredients: quercetin, rhamnazin, and isofucosterol. GO and EKGG indicated that the mechanism of action might be related to the PI3K/AKT signaling pathway as well as the regulation of cell motility and cell migration. Molecular docking and pharmacokinetic analyses suggest that quercetin and isoprostanoid sterols may have therapeutic value and safety for EC. The experiments confirmed that GpM can inhibit EC cell proliferation, migration, and invasion and suppress PI3K and AKT phosphorylation.

Conclusion

Our findings indicate that GpM exerts its anti-tumor effect on EC by inhibiting EC cell migration and invasion downregulation of the PI3K/AKT signaling pathway. Hence, we have reason to believe that GpM could be a promising candidate for the treatment of EC.

© 2025 Bentham Science Publishers
© 2025 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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Network Pharmacology Analysis and In Vitro Validation of the Active Ingredients and Potential Mechanisms of Gynostemma Pentaphyllum Against Esophageal Cancer
Comb Chem High Throughput Screen 28, 500 (2025); https://doi.org/10.2174/0113862073280183240108113853
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/content/journals/cchts/10.2174/0113862073280183240108113853
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  • Article Type:     Research Article
Keyword(s): esophageal cancer; Gynostemma pentaphyllum; KYSE-150; molecular docking; network pharmacology; PI3K/AKT

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