From plant to potential therapy: antioxidant and anticancer potential of Medicago lupulina and Trifolium arvense

BACKGROUND: Natural products with strong antioxidant properties and selective cytotoxic effects are increasingly recognized as promising candidates for cancer-related applications. In this context, Medicago lupulina and Trifolium arvense have garnered interest due to their diverse phytochemical profiles. This study aimed to compare the antioxidant potential and cytotoxic activity of methanolic and ethyl acetate extracts obtained from the aerial parts of both species. RESULTS: The methanolic extract of T. arvense exhibited the highest total phenolic and flavonoid contents, with values of 47.46 mg GAEs g−1 and 42.28 mg REs g−1, respectively. It demonstrated excellent antioxidant activity, with strong radical scavenging capacities (DPPH and ABTS values of 47.37 mg TEs g−1 and 95.18 mg TEs g−1). Meanwhile, M. lupulina extracts, especially the ethyl acetate one, showed significant metal chelating activity at 17.89 mg EDTAs g−1. In cytotoxicity tests, T. arvense's methanolic extract had a strong antiproliferative effect on HeLa cancer cells, with half-maximal inhibitory concentration (IC50) values of 0.492, 0.954, and 0.515 mg mL−1 at 24, 48, and 72 h, respectively, and lower toxicity towards L929 fibroblast cells. All results were statistically significant (P < 0.05). CONCLUSION: The methanolic extract of T. arvense has been identified as a powerful source of natural antioxidants that exhibit selective anticancer properties. This highlights its potential importance for future pharmaceutical and nutraceutical applications. These findings establish a strong scientific foundation for further in vivo and mechanistic studies. © 2026 Society of Chemical Industry.