Integrating Metabolomics Data, Network Pharmacology, and Molecular Docking to Investigate the Effect of Aging Times...

Liupao tea (LPT) undergoes significant bioactive changes during aging, while the link between these chemical shifts and the regulation of oxidative stress pathologies remains unclear. Therefore, this study integrated metabolomics, network pharmacology, and molecular docking to analyze Maosheng (MS) and Tianyu (TY) LPT samples aged 0-15 and 0-10 years, respectively, and elucidated the potential mechanisms of LPT in five oxidative stress - related diseases, including depression, obesity, Alzheimer's disease, diabetes, and hypertension. Metabolomics identified 42 and 13 core antioxidant metabolites in MS and TY samples, respectively. Among them, core metabolites in MS peaked at 5 years, while TY sustained high abundance levels from 3 to 8 years. Network pharmacology revealed synergistic regulation of all five pathologies by both LPTs, and eight key components were screened from MS, and nine from TY based on degree values. Interestingly, the highest node density was shown in depression, and Sankey connectivity confirmed its strongest modulatory effect. Besides, the core depression‑related components and targets were subjected to molecular docking simulations, and binding energies ranged from - 5.37 to -8.88 kcal/mol for MS components, as well as from - 4.11 to -8.39 kcal/mol for TY components. Importantly, oleaside A and CCRIS 7793 showed the strongest affinities for GAPDH and AKT1, respectively. In general, these results laid a practical foundation for developing an LPT product aimed at relieving oxidative stress-related health issues.