Bioactive extract and component from fruit spikes of Prunella vulgaris L. induce apoptosis in non-small cell lung cancer: An integrative network pharmacology, molecular docking, and experimental validation approach

Given the growing burden of lung cancer and the need for safer, mechanism-based interventions, functional natural products with radical-scavenging and apoptosis-modulating capacities have attracted increasing attention. Prunella vulgaris L., used in traditional Chinese medicine (TCM) as functional material, has been recognized for the health‑promoting properties. This study aimed to investigate the radical‑scavenging potential and apoptosis‑modulating effects of fruit spikes of P. vulgaris through an integrated network pharmacology, molecular docking, and experimental validation framework. Different solvent extracts and isolated compounds were prepared and screened for cytotoxicity against A549 cells and safety in HaCaT keratinocytes. The most active ethyl acetate extract (EtOAc) was further subjected to compounds isolation. Western blotting assessed apoptosis-related proteins, and molecular docking examined interactions. The results indicated the EtOAc extract possessed the highest total flavonoid content (TFC) and selective cytotoxicity toward A549 cells with minimal toxicity to HaCaT cells. Among the isolated compounds, quercetin (4), luteolin (5), rhein (6), and ursolic acid (7) exhibited notable cytotoxicity toward A549 cells, with quercetin (4) presenting the highest margin of safety (MOS). Western blot analysis revealed that the EtOAc extract and quercetin (4) modulated mitochondrial apoptosis by regulating B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), Caspase‑3, and protein kinase B (AKT). These findings provide mechanistic support for suggesting the fruit spikes of P. vulgaris may serve as a source of functional extracts and apoptosis‑inducing agents and worth further investigation for development of anticancer candidates.