Restoration of PPD-Induced Injury in iHDPCs via the OS–Mitochondrial Apoptosis Pathway: Screening and Validation of Natural Compounds

This study aimed to investigate the protective effects of curcumin (Cur), resveratrol (Res), and astragaloside IV (AS-IV) against p-phenylenediamine (PPD)-induced injury in human immortalized dermal papilla cells (iHDPCs), with a focus on phenotypic endpoints that are suggestive of the oxidative stress–mitochondrial apoptosis pathway. Putative core targets were predicted via network pharmacology and molecular docking, and cellular responses were evaluated using CCK-8, DCFH-DA, JC-1, and Annexin V/PI assays in both PPD- and H2O2-exposed models. 1623 Collectively, these observations are consistent with the possibility that Cur, Res, and AS-IV may alleviate PPD-induced cellular damage, potentially through modulation of oxidative status and mitochondrial homeostasis. However, because the current experiments do not directly measure NRF2 nuclear translocation, downstream antioxidant enzyme expression (e.g., P-AKT HO-1, NQO1), BAX/BCL-2 ratio, cytochrome c release, or caspase activation, they cannot establish target engagement or a definitive causal link to the proposed pathway. Therefore, our findings should be interpreted as correlative and hypothesis-generating; direct mechanistic validation is required to confirm the involvement of this pathway. Nevertheless, the consistent protective phenotypes observed make these compounds, particularly AS-IV, promising candidates for the development of next-generation hair dyes.