Therapeutic potential of Artemisia Kurramense against Helicobacter pylori infection-associated gastric pathogenesis: A network pharmacology, molecular docking, and DFT study

Introduction: Artemisia Kurramense has been used for gastrointestinal and inflammatory conditions, but no attempt has been made to explore the possible computational molecular mechanism against Helicobacter pylori-associated gastric pathogenesis. This study aimed to develop a computational hypothesis of the therapeutic potential of A. Kurramense by combining the phytochemical profiling based on LC-HRMS with network pharmacology, molecular docking and density functional theory (DFT) analysis. Methods: LC-HRMS profiling of three extracts of A. Kurramense resulted in the identification of 40 phytochemicals, of which 37 were unique across all three extracts analyzed. Oral bioavailability and drug-likeness screening were carried out for the identified compounds, which were then subjected to target prediction, disease-associated target intersection, protein–protein interaction (PPI) network analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking study and density functional theory (DFT) calculation. Results: Integrated analysis identified 131 common therapeutic targets, with AKT1, PIK3CA, and EGFR as prominent hub targets. Functional enrichment identified the PI3K-Akt pathway as the top enriched pathway, followed by cancer pathways, HIF-1, FoxO, MAPK and apoptosis pathways. Key regulatory proteins in the PI3K-Akt network were AKT1, PIK3CA, EGFR, PIK3R1 and TP53. The prioritized phytochemicals showed good predicted binding affinity with AKT1, with the greatest affinity for quercetin (AK-7) (−10.047 kcal/mol). At the same time, the DFT analysis revealed favourable electronic properties and chemical reactivity of the prioritized compounds. Conclusion: The computational results support a hypothesis that A. Kurramense is a multi-target modulator of host inflammatory, survival, oxidative-stress, and apoptosis-related signaling pathways, with the PI3K-Akt signaling pathway as a potential central mechanism of action. Some prioritized phytochemicals, such as quercetin, are promising for further investigation. However, these are computational predictions and further studies to validate the anti-H. pylori activity, target engagement, pathway modulation, and gastric protective effects require appropriate in vitro and in vivo studies.