Bioactive Aromatic Plant Extracts Modulate Metabolism and Inflammation in HeLa Cells

Aromatic plants are rich sources of bioactive compounds with recognized therapeutic potential. This study investigated the phytochemical composition and biological activities of ethanolic extracts from four aromatic species-Thymus vulgaris L. (thyme), Rosmarinus officinalis L. (rosemary), Aloysia citrodora (lemon verbena), and Tanacetum balsamita L. (costmary)-using HeLa human cancer cells as a model. LC-MS analysis identified 28-44 metabolites per species, with phenolic compounds and terpenoids comprising 58-67% of total metabolites. Biological assays demonstrated concentration-dependent inhibition of HeLa cell metabolism down to 150 µg/mL, with rosemary displaying the strongest effects. LDH assays confirmed membrane disruption, most notably for lemon verbena (ca. 80% of release), and cellular proliferation was significantly disrupted by all extracts, most notably for thyme (70% reduction). Under oxidative conditions, costmary, thyme, and lemon verbena reduced intracellular ROS by up to 35% and all extracts suppressed IL-6 secretion, with rosemary showing the strongest anti-inflammatory response, lowering IL-6 levels to near or below the assay's detection limit. Out of all the extracts, rosemary exhibited the most pronounced effects across cytotoxic, antioxidant, and cytokine assays, suggesting synergistic activity of its phenolic and terpenoid constituents. Multivariate analyses (correlation and PCA) linked specific metabolite classes to bioactivity patterns, providing insight into the mechanistic diversity underlying plant-specific effects. Overall, the results support the potential of these aromatic plants as sources of multifunctional bioactive compounds with anticancer and anti-inflammatory properties.