Ferula sinkiangensis against gastric cancer: a network pharmacology, molecular docking and cell experiment study

Abstract

Background Ferula sinkiangensis ( F. sinkiangensis ) is a traditional Chinese medicine that has been used for thousands of years to treat stomach ailments. To identify the main active compounds and explore the mechanisms underlying the therapeutic effect of F. sinkiangensis against gastric cancer (GC) by network pharmacology, molecular docking analysis and cell experiment. Methods Based on a review of the literature and previous experiments conducted by our research group, the active compounds of F. sinkiangensis were obtained. Active compounds and their target genes were screened from SwissADME, Pubchem, and Pharmmapper databases. GC-related target genes were obtained from GeneCards. The drug-compound-target-disease (D-C-T-D) network and protein-protein interaction (PPI) network were constructed by Cytoscape 3.7.2 and STRING database, and the core target genes and core active compounds were identified. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using the R package clusterProfiler. The core genes with high expression in GC were screened, which correlated with a poor prognosis using the GEPIA, UALCAN, HPA, and KMplotter databases. KEGG signaling pathway analysis was further conducted to predict the mechanism of F. sinkiangensis during the process of GC inhibition. The AutoDock vina 1.1.2 program was used to verify the molecular docking of the core active compounds and core target genes. MTT, Transwell, and Wound healing assay were used to detect the effects of ethyl acetate extract of F. sinkiangensis on the proliferation, invasion, and apoptosis of GC cells. Results Final results indicated that the active compounds include Farnesiferol C, Assafoetidin, Lehmannolone, Badrakemone, etc. The identified core target genes were GPI , TKT , GLYCTK , ERBB2 , GAPDH , etc. The Glycolysis/Gluconeogenesis pathway and the Pentose Phosphate pathway might play important roles in the treatment of GC with F. sinkiangensis . The data from the study showed that F. sinkiangensis was able to inhibit the proliferation of GC cells. Meanwhile, F. sinkiangensis remarkedly repressed the invasion and migration of GC cells in in vitro experiment. Conclusions This study revealed that F. sinkiangensis has an antitumor effect in in vitro experiment, and that the mechanism of F. sinkiangensis in GC treatment shows characteristics of multi-components, multi-targets, and multi-pathways, which provides a theoretical basis for its...

Unraveling the Therapeutic Mechanism of Saussurea involucrata against Rheumatoid Arthritis: A Network Pharmacology and Molecular Modeling-Based Investigation

“…These selected components, along with the components obtained from literature searches, were used to query the PubChem database (pubchem.ncbi.nlm.nih.gov, accessed on 12 April 2023) using the pubchempy Python toolkit, acquiring the Simplified Molecular Input Line Entry System (SMILES) notations. These notations were then imported into the SwissADME database (www.swissadme.ch, accessed on 16 April 2023) and subjected to screening based on criteria such as a gastrointestinal absorption (GI) rating of "High" and drug-likeness having two or more items marked as "Yes" [29]. Subsequently, the screened components were combined with the components directly obtained from the TCMSP database and underwent a further screening within TCMSP according to the standards of an oral bioavailability (OB) threshold of ≥30%, a drug-likeness (DL) threshold of ≥0.18, and a Caco-2 permeability threshold of ≥−0.4 [30,31].…”