Valorization of Tomato Leaves: Optimization of Eco-Friendly Phenolic Extraction and Assessment of Biological Activities

Tomato leaves, typically discarded during harvest, are a rich yet underutilized source of bioactive compounds. This study aimed to valorize tomato leaves by optimizing the extraction of their phenolic compounds using a water-based method and response surface methodology. The optimal conditions, notably heating a mixture of 1:50 solid-to-liquid ratio at 71 °C for 29 min, yielded the most total phenolic content and antioxidant activity. The biological activities of the lyophilized tomato leaf extract (TLE) were then assessed. TLE showed dose-dependent antimicrobial activity against Escherichia coli and Candida albicans, but neither against Pseudomonas aeruginosa nor Staphylococcus aureus. In addition, it demonstrated moderate cytotoxicity against MCF-7 breast cancer cells with an IC50 value of 114.5 µg/mL. Interestingly, the extract significantly reduced intracellular reactive oxygen species levels in RAW 264.7 macrophages, supporting its anti-inflammatory potential. LC-MS analysis identified rutin (45.21%), 4-hydroxycoumarin (13.60%), and α-tomatine (12.37%) as the major chemical constituents in TLE, suggesting contributing effects behind the observed bioactivities. These results support the potential of tomato leaf extract as an eco-friendly source for functional ingredients, transforming agricultural waste through green extraction into valuable applications for nutraceuticals and sustainable product development.