Dyspepsia, or indigestion, is a condition marked by discomfort in the upper gastrointestinal tract, and existing treatments for functional dyspepsia often yield limited results. This study investigates the potential of Zingiber officinale (ginger) in treating dyspepsia using network pharmacology and molecular dynamics approaches. A total of 31 bioactive compounds were identified, targeting 29 proteins associated with dyspepsia. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed 160 related pathways (p-value ≤ 0.05), including the phosphatidylinositol-3-kinase/Akt signaling pathway, gastric cancer, and nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. A compounds–targets–pathways (C-T-P) network highlighted the central roles of epidermal growth factor receptor (EGFR) and Ras-related C3 botulinum toxin substrate -alpha serine/threonine-protein kinase (AKT1) in modulating inflammatory responses and proliferation of gastrointestinal epithelial cells, with significant implications in the pathogenesis of gastrointestinal disorders, validated via molecular docking. Compounds such as 3,5-diacetoxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane (DDMHMH), alpha-tocopherol, gingerol, and shogaol showed good binding (ΔGbinding < −5.00 kcal/mol). Molecular dynamics simulations for 50 ns confirmed the stability of DDMHMH–AKT1 and DDMHMH–EGFR complexes. Binding free energy (Molecular mechanics/Poisson–Boltzmann surface area) calculations supported strong interactions, with ΔGbinding values of −8.71 kcal/mol (AKT1–DDMHMH) and −11.44 kcal/mol (EGFR–DDMHMH). These findings support Z. officinale’s potential for dyspepsia therapy.
Simatupang ST, Dermawan D, Nadia, Tan S, Tjandrawinata RR. Network pharmacology and molecular dynamics studies unveil the therapeutic mechanisms of Zingiber officinale against dyspepsia. J Appl Pharm Sci. 2025. Article in Press. http://doi.org/10.7324/JAPS.2025.240961
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