Isolation of an angiotensin converting enzyme (ACE) inhibitor from Olea europaea and Olea lancea

The aqueous extract of the leaves of Olea europaea and Olea lancea both inhibited Angiotensin Converting Enzyme (ACE) in vitro. A bioassay-directed fractionation resulted in the isolation of a strong ACE-inhibitor namely the secoiridoid 2-(3,4-dihydroxyphenyl)ethyl 4-formyl-3-(2-oxoethyl)-4E -hexenoate (oleacein) (IC50 = 26 mu M). Five secoiridoid glycosides (oleuropein, ligstroside, excelcioside, oleoside 11-methyl ester, oleoside) isolated from Oleaceous plants showed no significant ACE-inhibition whereas, after enzymatic hydrolysis, the ACE-inhibition at 0.33 mg/ml was between 64% to 95%. Secoiridoids have not been described previously in the literature as inhibitors of ACE. Oleacein showed a low toxicity in the brine shrimp (Artemia salina)lethality test (LC(50) (24 h) = 969 ppm).