Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC50 determination. The IC50 values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results.

Cocoa is a food rich in polyphenols, mainly the flavonoid procyanidins and flavan-3-ols. The improvement of the cardiovascular function in humans upon cocoa consumption has been specifically linked to the presence of flavan-3-ol derived metabolites in plasma, especially epicatechin glucuronide. In this context, a flavonoid-enriched cocoa-derived product could potentially exert stronger health benefits. The aim of the present study was to obtain a cocoa powder with a higher flavonoid content (mainly enriched in monomer compounds) and assess its flavonoid bioavailability in humans. For this purpose, an unfermented, nonroasted, and blanch-treated cocoa powder (A) was obtained. The powder contained four times more procyanidins than a conventional (B) cocoa powder. Powder A contained eight times more epicatechin and procyanidin B2 than powder B. Cocoa milk drinks were prepared with powder A (MDA) and B (MDB). The bioavailability of flavonoids in both drinks was assessed in a crossover intervention with healthy volunteers. The content of epicatechin glucuronide, the main metabolite detected in plasma, was five-fold higher upon consumption of MDA as compared with MDB. The urinary excretion of metabolites, mainly methyl epicatechin sulfate, was higher upon MDA consumption as compared with MDB, ranging from two-to 12-fold higher depending on the metabolite. These results, together with previous reports regarding the cardiovascular benefits linked to the presence of procyanidin metabolites in plasma, suggest that further clinical trials to validate the health benefits of a flavonoid-enriched cocoa powder are warranted.

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