Objective Molecular mechanism, core target, and associated pathway of the cell senescence delaying effect of epigallocatechin gallate (EGCG) were investigated by bioinformatics and a cellular experiment.

Method Bioinformatics methods, including network pharmacology and transcriptomics, were used to analyze the aging- and EGCG-related datasets for identifying the target genes and related pathways. Molecular docking was employed to decipher the mechanisms associated with the senescence-delaying function. The Aβ_25-35-induced PC12 cell model was applied to verify the mechanism using viability assays, reactive oxygen species detection, staining, and RT-qPCR.

Result A network pharmacology analysis revealed that there were 173 EGCG intersection targets related to aging. And the PPI network and cluster analysis determined the core genes to include STAT3 and AXL. The combined transcriptomics analysis further narrowed the search down to 7 key genes. Ultimately, STAT3 was the sole target gene, and EGFR the core pathway, identified by multiple analyses. The molecular docking of EGCG with STAT3 was significant (−8.6 kcal·mol⁻¹), and their hydrogen bonding and hydrophobic interaction were stable and inhibitive for abnormal activations of STAT3. The Aβ_25-35-induced PC12 cell model showed that EGCG could significantly restore nerve cell viability, reduce intracellular reactive oxygen species, and down-regulate STAT3 mRNA expression.

Conclusion EGCG exerted a cell senescence-delaying effect by directly binding to STAT3, an identified target that inhibited neuronal cell senescence and EGFR signaling pathway.