Chemical Profiling, Antioxidant Activity, and Computational Exploration of Potential Cytoprotective Mechanisms of Talinum paniculatum via Metabolomics and QSAR Approaches

Talinum paniculatum exhibits significant antioxidant capacity, however the specific bioactive metabolites and molecular mechanisms underlying this capacity remain to be elucidated. In this study, ethanol extracts from the underground parts (roots, TP-ER) and aerial parts (stems and leaves, TP-ESL) of T. paniculatum were prepared to determine total phenolic and flavonoid contents, as well as to conduct in vitro antioxidant assays, and evaluate the cytoprotective effect against H2O2-induced oxidative stress in HepG2 cells. In all assays, TP-ER exhibited higher activity than TP-ESL under the tested conditions. Subsequently, widely targeted metabolomics analysis was conducted on the two extracts to annotate their metabolites. Genes associated with oxidative damage were screened computationally using the Gene Expression Omnibus (GEO) database. Three p53 pathway genes (CDKN1A, JUN, and PMAIP1) were prioritized as candidate targets for further investigation. Quantitative Structure–Activity Relationship (QSAR) models were constructed as exploratory pooled classifiers using reported activity datasets from ChEMBL to prioritize annotated metabolites with potential activity within the combined p53-related target dataset. This classifier does not assign activity to individual targets. Three annotated metabolites were predicted to be potentially active, including two steroids and one alkaloid. Molecular docking prioritized N-Caffeoyl-4-O-methyldopamine and norflickinflimiod F as candidate metabolites with favorable predicted binding to PCNA/NFAT1 and the NOXA BH3 interface, respectively. These findings provide a preliminary chemical basis for further investigation of the antioxidant and cytoprotective effects of T. paniculatum and generate testable mechanistic hypotheses that require experimental validation in future studies.