J. Pharm. Pharmacol. 1999, 51: 971±974 # 1999 J. Pharm. Pharmacol. Received January 29, 1999 Accepted March 9, 1999 On the In-vitro Antimicrobial Activity of Oleuropein and Hydroxytyrosol GIUSEPPE BISIGNANO, ANTONIO TOMAINO, ROSSELLA LO CASCIO, GIUSEPPE CRISAFI, NICOLA UCCELLA* AND ANTONELLA SAIJA { Department Farmaco-Biologico, University of Messina,*CIRASAIA, University of Calabria, and { Department of Pharmacology of Natural Substances and General Physiology, University of Rome `La Sapienza', Italy Abstract Secoiridoides (oleuropein and derivatives), one of the major classes of polyphenol contained in olives and olive oil, have recently been shown to inhibit or delay the rate of growth of a range of bacteria and microfungi but there are no data in the literature concerning the possible employment of these secoiridoides as antimicrobial agents against pathogenic bacteria in man. In this study ®ve ATCC standard bacterial strains (Haemophilus in¯uenzae ATCC 9006, Moraxella catarrhalis ATCC 8176, Salmonella typhi ATCC 6539, Vibrio parahaemo- lyticus ATCC 17802 and Staphylococcus aureus ATCC 25923) and 44 fresh clinical isolates (Haemophilus in¯uenzae, eight strains, Moraxella catarrhalis, six strains, Salmo- nella species, 15 strains, Vibrio cholerae, one strain, Vibrio alginolyticus, two strains, Vibrio parahaemolyticus, one strain, Staphylococcus aureus, ®ve penicillin-susceptible strains and six penicillin-resistant strains), causal agents of intestinal or respiratory tract infections in man, were tested for in-vitro susceptibility to two olive (Olea europaea) secoiridoides, oleuropein (the bitter principle of olives) and hydroxytyrosol (derived from oleuropein by enzymatic hydrolysis and responsible for the high stability of olive oil). The minimum inhibitory concentrations (MICs) calculated in our study are evidence of the broad antimicrobial activity of hydroxytyrosol against these bacterial strains (MIC values between 024 and 785 mg mL 1 for ATCC strains and between 097 and 3125 mg mL 1 for clinically isolated strains). Furthermore oleuropein also inhibited (although to a much lesser extent) the growth of several bacterial strains (MIC values between 625 and 500 mg mL 1 for ATCC strains and between 3125 and 250 mg mL 1 for clinical isolates); oleuropein was ineffective against Haemophilus in¯uenzae and Moraxella catarrhalis. These data indicate that in addition to the potential employment of its active principles as food additives or in integrated pest-management programs, Olea europaea can be considered a potential source of promising antimicrobial agents for treatment of intestinal or respiratory tract infections in man. Despite the wide availability of clinically useful antimicrobial drugs, several arguments (limited antimicrobial spectrum and serious side-effects of major antibiotics, increasing clinical resistance of previously sensitive microorganisms, emergence of previously uncommon infections) stimulate the development of new plant molecules with anti- bacterial activity. Because the olive (Olea europaea) leaf is known to be resistant in nature to microbial and insect attack, much research has focused on the anti- microbial activity of compounds contained in olives, olive oil and vegetation waters. Correspondence: A. Saija, Department Farmaco-Biologico, University of Messina, Contrada Annunziata, 98168 Messina, Italy.