Olive-derived bioactive combinations: synergistic angiotensin-I-converting enzyme (ACE) inhibition and distinct mechanisms of triterpenic acids and phenolics.

BACKGROUND: Cardiovascular diseases, largely driven by hypertension, remain the leading cause of mortality worldwide. Angiotensin-I-converting enzyme (ACE) inhibition is a well-established therapeutic approach; however, synthetic inhibitors are frequently associated with adverse effects. Natural bioactive compounds, particularly those derived from olives, have been proposed as potential alternatives or complementary agents.

RESULTS: This study evaluated the ACE-inhibitory potential of olive-derived triterpenic acids (oleanolic acid (OA) and maslinic acid (MA)) and phenolic compounds (hydroxytyrosol (HT), 3,4-dihydroxyphenylglycol (DHPG), verbascoside (VER), luteolin (LUT), and comselogoside (COM)). Among the individual compounds, OA (half-maximal inhibitory concentration (IC50) = 18.43 μmol L-1) and MA (IC50 = 25.66 μmol L-1) exhibited the strongest ACE inhibition, acting through different mechanisms: OA as a competitive, MA as an uncompetitive, and COM as a non-competitive inhibitor. Notably, certain binary combinations revealed notable interactions, particularly HT:COM, which displayed strong synergistic inhibition at concentrations where individual components were inactive. In contrast, combinations such as COM:MA and COM:LUT demonstrated additive or antagonistic effects depending on molar ratios and concentration.

CONCLUSIONS: These findings highlight the potential of individual olive-derived compounds, especially OA and MA, as natural ACE inhibitors with distinct mechanisms of action. Moreover, specific synergistic interactions, such as HT:COM, represent promising candidates for the development of safer and more effective dietary interventions in hypertension management. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.