Screening of Mediterranean Plant-Derived Extracts for Antioxidant Effect in Cell-Free and Human Cell Line Models

Oxidative stress plays a critical role in the development of various chronic diseases, leading to major health problems worldwide. There has been increasing interest in using natural antioxidants as complementary agents for maintaining redox homeostasis and assuring a healthy lifestyle. This study aimed to systematically screen the antioxidant potential and cytotoxicity profiles of 19 plant-derived extracts using both a cell-free Fenton reaction-based assay and human monocytic THP-1 cells in vitro. The radical-scavenging capacity varied markedly among the extracts, with <i>Acalypha virginica</i> Linnaeus (ACALYPHA), <i>Acorus calamus</i> Linnaeus (ACORUS), <i>Actinidia deliciosa</i> (A.Chev.) C.F. Liang & A.R. Ferguson (ACTINIDIA), and <i>Heuchera sanguinea</i> Pursh (HEUCHERA) demonstrating strong activity in the chemical assay. In the cellular model, 15 extracts significantly reduced intracellular reactive oxygen species (ROS) levels without inducing cytotoxicity at effective concentrations. Notably, <i>Acalypha virginica</i> Linnaeus (ACALYPHA), <i>Actinidia deliciosa</i> (A.Chev.) C.F. Liang & A.R. Ferguson (ACTINIDIA), <i>Dianthus superbus</i> Linnaeus subsp. <i>superbus</i> (DIANTHUS), <i>Succisa pratensis</i> Moench (SUCCISA), and <i>Typha laxmannii</i> Lepech (TYPHA) exhibited consistent antioxidant efficacy across multiple doses. At higher concentrations, all extracts triggered apoptosis and/or necrosis, emphasizing the importance of defining safe ranges. These findings provide a comprehensive comparative analysis of Mediterranean plant-based natural antioxidants obtained by an in vitro approach. The selected plant extracts could be considered as promising candidates for the development of strategies targeting oxidative stress-related disorders. Further investigations considering the specific phytochemical composition of each extract and in vivo validation are needed to confirm their efficacy and safety.