The effective compounds and mechanisms of Guiqi-Qizao-Gao in anti-aging based on UPLC/Q-TOF-MS/MS, network pharmacology, molecular docking, molecular dynamics simulation

Guiqi-Qizao-Gao (GQG), a clinically used formulation derived from the classical prescription Danggui Buxue Tang and categorized as a " food-medicine homologous ", has demonstrated efficacy in improving anemia, fatigue, and immune function. However, its anti-aging mechanisms remain unclear. This study aims to elucidate the anti-aging components of GQG and their underlying mechanisms of action. The chemical constituents of GQG were analyzed using UPLC/Q-TOF-MS/MS. Potential targets of the identified compounds were predicted through the Swiss Target Prediction database. Aging-related targets were retrieved from DisGeNET, GeneCards, DrugBank, OMIM, and TTD databases. Compound-target and protein-protein interaction (PPI) networks were constructed to identify key therapeutic targets. To elucidate the underlying mechanisms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed. A "compound-target-pathway" network was established to screen high-scoring bioactive compounds. Finally, molecular docking and molecular dynamics (MD) simulations were conducted to validate the binding interactions between the active compounds and their respective targets. UPLC/Q-TOF-MS/MS analysis identified 41 chemical constituents in GQG, including flavonoids, organic acids, and triterpenoids. The constructed "component-target-disease" network revealed that 5-demethylnobiletin, scrophulein, mosloflavone, and tangeretin were the top-ranked potential active constituents in GQG. Protein-protein interaction (PPI) network analysis identified SRC, AKT1, HSP90AA1, STAT3, and ESR1 as core targets, with the largest cluster in the network highlighting SRC, EGFR, and PTK2 as the top three hub genes. Functional enrichment analysis demonstrated that GQG exerts its effects primarily by modulating the positive regulation of protein phosphorylation, insulin-like growth factor receptor signaling pathway, insulin receptor signaling pathway, and PI3K-Akt and Rap1 signaling pathways. Molecular docking and molecular dynamics simulations confirmed strong binding capabilities between the active compounds and tested targets.This study identifies the active compounds in GQG and proposes a potential mechanism for its anti-aging activity. These results suggest future directions for the prevention and treatment of age-related diseases. In summary, these findings provide a scientific basis for the development of GQG-based interventions in aging and related disorders.