Phytochemical Profile and In Vitro Cytotoxic, Genotoxic, and Antigenotoxic Evaluation of Cistus monspeliensis L. Leaf Extract

<i>Cistus monspeliensis</i> L. (<i>C. monspeliensis</i>) is used in Italian folk medicine. This study was performed to determine genotoxic and antigenotoxic effects of <i>C. monspeliensis</i> leaf extract against mitomycin C (MMC) using an in vitro cytokinesis-block micronucleus assay (CBMN) in the Chinese Hamster Ovarian K1 (CHO-K1) cell line. The phytochemical composition of <i>C. monspeliensis</i> extract was evaluated using an untargeted metabolomic approach by employing UPLC-PDA-ESI/MS. The automated in vitro CBMN assay was carried out using image analysis systems with a widefield fluorescence microscope and the ImageStreamX imaging flow cytometer. The phytochemical profile of <i>C. monspeliensis</i> extract showed, as the most abundant metabolites, punicalagin, myricetin, gallocathechin, and a labdane-type diterpene. <i>C. monspeliensis</i>, at the tested concentrations of 50, 100, and 200 μg/mL, did not induce significant micronuclei frequency, thus indicating the absence of a genotoxic potential. When testing the <i>C. monspeliensis</i> extract for antigenotoxicity in the presence of MMC, we observed a hormetic concentration-dependent effect, where low concentrations resulted in a significant protective effect against MMC-induced micronuclei frequency, and higher concentrations resulted in no effect. In conclusion, our findings demonstrate that <i>C. monspeliensis</i> extract is not genotoxic and, at low concentration, exhibits an antigenotoxic effect. In relation to this final point, <i>C. monspeliensis</i> may act as a potential chemo-preventive against genotoxic agents.