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Activity-Guided Discovery of (S)-Malic Acid 1′-O-β-Gentiobioside as an Angiotensin I-Converting Enzyme Inhibitor in Lettuce (Lactuca sativa)

Lagemann, Annika, Dunkel, Andreas, Hofmann, Thomas
Journal of agricultural and food chemistry 2012 v.60 no.29 pp. 7211-7217
Lactuca sativa, aldosterone, angiotensin I, angiotensin II, antihypertensive agents, blood pressure, fractionation, functional foods, glycosidases, glycosides, hydrochloric acid, hydrolysis, inhibitory concentration 50, ion exchange chromatography, lettuce, nuclear magnetic resonance spectroscopy, peptidyl-dipeptidase A, phytochemicals, renin, saliva, stomach
Angiotensin-converting enzyme (ACE), playing a crucial role in the renin angiotensin aldosterone system, is well-known to catalyze the conversion of the decapeptide angiotensin I into the physiologically active octapeptide angiotensin II, triggering blood pressure increasing mechanisms. To meet the demand for natural phytochemicals as antihypertensive agents in functional food development, extracts prepared from a series of vegetables were screened for their ACE-inhibitory activity by means of a LC-MS/MS-based in vitro assay. By far the highest ACE inhibition was found for a lettuce extract, in which the most active compound was located by means of activity-guided fractionation. LC-MS, NMR spectroscopy, and hydrolysis experiments followed by ion chromatography led to the unequivocal identification of the ACE inhibitor as the previously not reported (S)-malic acid 1′-O-β-gentiobioside. This glycoside represents a novel class of ACE-inhibiting phytochemicals with a low IC₅₀ value of 27.8 μM. First incubation experiments in saliva and aqueous hydrochloric acid demonstrated the stability of (S)-malic acid 1′-O-β-gentiobioside against salivary glycosidases and stomach acid.