This study aimed to evaluate the inhibitory potential of phenolic-rich extracts from selected medicinal plants belonging to the Lamiaceae and Asteraceae families against the furin protease enzyme, a key target in viral and oncogenic pathways. Extracts of Origanum vulgare, Thymus vulgaris, Mentha piperita, Mentha spicata, Salvia officinalis, and Silybum marianum were prepared using hexane, chloroform, and ethyl acetate. Phenolic compounds were quantified using High-Performance Liquid Chromatography (HPLC). Furin inhibition was assessed spectrophotometrically and analyzed statistically with multivariate approaches. The chloroform extract of Origanum vulgare exhibited 97.44 ± 0.12% inhibition, while the ethyl acetate extract of Mentha spicata showed 97.44 ± 0.08% inhibition. Epicatechin and rutin displayed significant synergistic effects, while naringenin negatively affected inhibition (p < 0.05). Solvent polarity significantly influenced phenolic diversity and biological activity, with ternary combinations showing 33% higher inhibition than single compounds. These findings highlight phenolic blends as promising natural furin inhibitors, with chloroform being optimal for broad-spectrum extraction.
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