Abstract

Gynostemma pentaphyllum is commonly used to treat various tumors in China. The aim of the study is to explore the pharmacological mechanism of Gynostemma pentaphyllum in gastric cancer using joint network pharmacology, molecular docking and in vitro experimental verification. First, the active constituents and potential targets of Gynostemma pentaphyllum were screened from a public database and screening of core targets anti-gastric cancer using protein-protein interaction networks. The Cancer Genome Atlas and Human Protein Atlas databases were used to evaluate the messenger ribonucleic acid and protein expression of core target genes in normal gastric epithelium and gastric cancer tissues and their relationship with overall survival in gastric cancer. Functional and pathway enrichment analyses of the potential targets were performed using gene ontology and Kyoto encyclopedia of genes and genomes. Fifteen active components and all related targets of Gynostemma pentaphyllum were retrieved from the Traditional Chinese Medicine Systems Pharmacology database and 127 potential targets were identified by intersection with colorectal cancer-related targets. Protein-protein interaction network analysis showed that six target genes, AKT serine/threonine kinase 1, Jun proto-oncogene and B-cell lymphoma 2 proteins were key genes. Gene ontology enrichment analysis involved 1892 BP, 37 CC and 142 MF. Kyoto encyclopedia of genes and genomes enrichment analysis showed that the anti-cancer effects of Gynostemma pentaphyllum were mediated by advanced glycation end products-receptor for advanced glycation end products, interleukin-17, hypoxia inducible factor 1 and transforming growth factor signalling pathways. Molecular docking revealed that the three core target proteins stably bound to quercetin and rhamnazin. The results of the in vitro experiments showed that both quercetin and rhamnazin inhibited the activity of gastric cancer cells, up-regulated the messenger ribonucleic acid and protein AKT serine/threonine kinase 1 and down-regulated Jun proto-oncogene and B-cell lymphoma 2 protein activities at the specified concentrations. This study revealed the potential role of Gynostemma pentaphyllum in the treatment of gastric using network pharmacology, molecular docking and in vitro experiments.