Deciphering the mechanism and substance basis of Dingxiang Shidi Decoction for the treatment of chemotherapy-induced nausea and vomiting by integrating mass spectrometry, network pharmacology and molecular docking.

Abstract

BackgroundChemotherapy-induced nausea and vomiting (CINV) remains a prevalent and debilitating side effect of cancer treatment with limited therapeutic options. Dingxiang Shidi Decoction (DXSD), a classical Chinese herbal formula, has demonstrated clinical efficacy in CINV management. However, its active components and mechanism of action require systematic investigation.ObjectiveThis study aims to elucidate the pharmacologically active constituents of DXSD and their anti-CINV mechanisms.MethodsWe employed advanced analytical techniques including UPLC-MS/MS and GC-MS to analyze the chemical components of DXSD. Network pharmacology techniques were applied to explore its pharmacological mechanisms. And molecular docking simulation was conducted to further refine the drug-target interaction.ResultsA total of 292 chemical compounds were identified in DXSD, comprising 165 water-soluble components, 56 volatile components, and 84 network database entries. By integrating 564 drug targets with 888 CINV disease targets, we identified 143 potential therapeutic targets. Further protein-protein interaction (PPI) network analysis revealed 12 key active ingredients and 13 key therapeutic targets. Enrichment analysis suggested that DXSD may reduce inflammation, modulate neurotransmitter stimulation in the gastrointestinal tract, and regulate cellular proliferation and differentiation. Notably, key active ingredients, predominantly aromatic compounds such as sabinene, (-)-α-cubebene, α-copaene, β-caryophyllene, aromandendrene, γ-muurolene, (-)-α-muurolene, α-phellandrene, α-terpinene, γ-terpinene, (+)-δ-cadinene, and Gomisin B, demonstrated significant binding affinity with multiple targets, particularly AKT1, BCL2, EGFR, MTOR, and STAT3.ConclusionsThis study reveals the active components and therapeutic mechanisms of DXSD against CINV, supporting its clinical application and demonstrating the potential of aromatherapy as an effective treatment strategy.