Synergistic Phenolic Compounds in Medicinal Plant Extracts: Enhanced Furin Protease Inhibition via Solvent-Specific Extraction from Lamiaceae and Asteraceae Families

This study aimed to evaluate the inhibitory potential of phenolic-rich extracts from selected medicinal plants belonging to the <i>Lamiaceae</i> and <i>Asteraceae</i> families against the furin protease enzyme, a key target in viral and oncogenic pathways. Extracts of <i>Origanum vulgare</i>, <i>Thymus vulgaris</i>, <i>Mentha piperita</i>, <i>Mentha spicata</i>, <i>Salvia officinalis</i>, and <i>Silybum marianum</i> 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 <i>Origanum vulgare</i> exhibited 97.44 ± 0.12% inhibition, while the ethyl acetate extract of <i>Mentha spicata</i> showed 97.44 ± 0.08% inhibition. Epicatechin and rutin displayed significant synergistic effects, while naringenin negatively affected inhibition (<i>p</i> < 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.