Assessment of Antioxidant Activity and Dose-Dependent Effect on Genotoxicity/Antigenotoxicity of Pulmonaria officinalis Ethanolic Extract

<b>Background/Objectives:</b><i>Pulmonaria officinalis</i> L., commonly known as lungwort, is a medicinal plant traditionally used for respiratory ailments, but its biological activities have not yet been sufficiently researched. The aim of this study was to investigate the antioxidant and dose-dependent genotoxic/antigenotoxic properties of a 70% ethanolic extract. <b>Methods:</b> Quantification of polyphenols and GC-MS analysis were performed in order to chemically characterize the extract. Antioxidant activity was evaluated through DPPH, PFRAP, total antioxidant capacity (TAC), and ferrous ion chelating assay (FIC). MTT and alkaline comet assay were used for investigation of cytotoxicity and geno/antigenotoxicity on normal fetal fibroblast cells (MRC-5). <b>Results:</b> The chemical analysis of the extract showed that the extract is rich in polyphenolics and that phytol is the most abundant compound, accompanied by terpenoids, fatty acids, alcohols, polyketides, and alkaloids. In addition, notable antioxidant capacity was detected in all tests applied. The extract reduced cell viability only at the highest concentration tested (33.7%). Furthermore, a dual dose-dependent effect was recorded since the genotoxic effect of the tested extract was observed at higher concentrations, while non-genotoxic concentrations showed protective effects against oxidative damage of DNA. Namely, pretreatment with lungwort extract reduced the DNA damage induced by H₂O₂, with the highest protective effect at the lowest tested concentration, indicating a hormetic mode of action. <b>Conclusions:</b> These results provide a solid foundation for future research into this medicinal plant, with the aim of its potential therapeutic use in the prevention of diseases associated with oxidative stress.