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Global Translational Medicine Impact of flavonoids on vascular health

carriers of the apo epsilon3/epsilon3 genotype, but not in number of polyphenolic extracts with a high flavanol
epsilon4 allele carriers. Lee et al. investigated the effect content, including cocoa extract, black or green tea, and
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of quercetin on cardiometabolic risks in healthy male red wine polyphenols, have demonstrated the ability to
smokers and observed notable drops in both systolic lower BP. 14,94
and diastolic BP in the quercetin-rich supplementation Studies on animals indicate that effective doses of
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group. Similarly, Larson et al. reported a decrease in BP pure epicatechin for antihypertensive effects range
in men with Stage 1 hypertension using acute quercetin from 10 to 350 mg/kg/day. It is noteworthy that doses
aglycone in a double-blind, placebo-controlled crossover below 5 mg/kg/day showed no signs of lowering BP.
design. However, this reduction did not coincide with In adult DOCA-salt rats, Gómez-Guzmán et al.
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changes in ACE activity, ET1 levels, or NO bioavailability, found that epicatechin significantly lowered BP and
and there were no alterations in vascular reactivity. These enhanced endothelium-dependent vasorelaxation.
findings are noteworthy as these mechanisms are typically Other hypertension models, including fructose-induced
considered principal contributors to BP reduction. hypertension, L-NAME-induced hypertension, and SHR,
Furthermore, quercetin intake exhibited a capacity to have also shown the BP-lowering benefits of epicatechin. 109
reduce systolic BP in women with Type 2 diabetes.
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However, inconsistent results have been observed, with Various studies have delved into the mechanisms
some studies reporting no significant BP reduction in underlying epicatechin’s antihypertensive effects. In
hypertensive subjects. 103,104 L-NAME-induced hypertension models, epicatechin
prevented BP increases, reduced oxidative stress, and
A recent meta-analysis combining the results of restored NO bioavailability. 109,110 However, Gómez-
seven randomized, placebo-controlled clinical trials Guzmán et al. highlighted that the antihypertensive
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demonstrated a substantial drop in BP with quercetin effects of epicatechin are dependent on the duration, dose,
supplementation. This effect may have been stronger at and specific disease conditions, showing antioxidative and
dosages over 500 mg/day, which are higher than those anti-inflammatory benefits but no significant effect on the
typically used. In fact, Vogiatzoglou et al. showed that development of hypertension with chronic epicatechin
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the typical European intake of flavonoids is lower than the administration. Additional effects of epicatechin include
dosages linked to notable health impacts. Pérez et al. lowering plasma levels of COX-2 and ET-1, inhibiting
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discovered that quercetin had a vasodilator effect on the ACE activity, improving the redox condition of cardiac
arteries of young, healthy humans; however, this increase tissue, improving vascular NO bioavailability to improve
in diameter in a major conduit artery did not result in endothelial function, and modulating cell signaling
changes in BP. This finding is crucial for the prevention of pathways. These multifaceted effects contribute to
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hypertension in normotensive individuals, as no reduction epicatechin’s antihypertensive properties.
in BP was observed in normal controls in pre-clinical and
clinical studies. Therefore, it appears that a certain degree There is a dearth of research on pure epicatechin
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of elevated BP may be a prerequisite for quercetin to exert in human trials, despite strong data supporting the
its BP-lowering effect. 30 cardiovascular benefits of products enriched with or
containing epicatechin in human investigations. While
The positive effects of quercetin on BP have been some clinical research has examined its potential benefits,
attributed to various mechanisms. These mechanisms more studies are necessary to draw firm conclusions
include ameliorating endothelial dysfunction through regarding epicatechin’s potential as an antihypertensive
the activation of eNOS, increasing NO bioavailability, agent. 112,113
direct vasodilatory action, and exhibiting antioxidant Dietary flavonoids, a diverse group of polyphenolic
and anti-inflammatory properties. 55,57,102 In addition, compounds, exhibit varied mechanisms for mediating
quercetin’s BP-lowering effect may involve direct renal BP-lowering effects. Unlike quercetin, which has no
protection. However, it remains unclear whether the effect on ACE activity, epicatechin appears to depend on
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in vivo antihypertensive effects are attributed to quercetin the suppression of ACE activity for its antihypertensive
itself or its metabolites. Despite these insights, the exact effects. The structural diversity of flavonoid subgroups
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mechanisms responsible for quercetin’s BP-lowering effect makes it challenging to pinpoint a singular mechanism.
remain partially unknown, with some studies presenting Overall, flavonoids are proposed to interact chemically
conflicting results. 107
with ROS and induce changes in various enzymes, ion
Apples, grapes, tea, and chocolate contain significant channels, and transcription factors. Potential mechanisms
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levels of epicatechin, which is a well-known bioactive contributing to the BP-lowering effects of flavonoids
flavanol. In experimental hypertension rat models, a include the improvement of endothelial function,

Volume 3 Issue 2 (2024) 10 doi: 10.36922/gtm.2458