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Global Translational Medicine Impact of flavonoids on vascular health

thrombi formation and cytoskeletal reorganization. Other a crucial role in BP control by influencing factors such
mechanisms involve inhibiting pathways like thrombocyte as blood volume, electrolyte balance, and vasodilation.
secretion, protein C breakdown, platelet activation factor, Kaempferol and quercetin interact with various components
and phospholipase C. Antiplatelet activity is also achieved of the RAAS to exert their antihypertensive actions.
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by blocking TXA formation and increasing intracellular The renin-mediated conversion of angiotensinogen to
cAMP and cGMP levels. Flavonoids inhibit enzymes like Ang I and the subsequent ACE-mediated conversion
phospholipase A and certain tyrosine kinases. 74 of Ang I to Ang II constitute the RAAS pathway. Ang
Glycoprotein (GP) Ib/IIa inhibitors, another facet of II, a potent vasoconstrictor, also stimulates aldosterone
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flavonoid action, bind to platelet receptors, preventing secretion, leading to sodium and water retention.
fibrinogen and vWF binding crucial for platelet aggregation. Studies indicate that kaempferol and quercetin can
Flavonoids like quercetin or catechin elevate NO levels, inhibit ACE activity, thereby reducing Ang II production
decreasing the expression of the GP Ib/IIa complex and and preventing excessive vasoconstriction, promoting
thereby blocking platelet aggregation in vitro. 75 vasodilation, and contributing to an overall reduction in
BP. In addition, these flavonols may influence aldosterone
4.2. Hypertension production, assisting in maintaining electrolyte balance

Hypertension is a clinical condition characterized by and preventing fluid retention. The ability of kaempferol
persistently elevated diastolic and/or systolic BP within and quercetin to modulate key components of the RAAS
the blood vessels. It is a leading cause of illness and underscores their potential as natural compounds for
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mortality. Contributing factors include obesity, a sedentary hypertension management. By targeting crucial elements
lifestyle, smoking, stress, and aging. NO, synthesized by of this regulatory system, these flavonols provide a holistic
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the endothelium, plays a pivotal role in vascular health . approach to BP control, addressing both vascular tone
Functioning as a vasodilator, NO regulates vascular tone by and fluid balance. It is important to note that the specific
inducing relaxation in blood vessels, thereby influencing mechanisms through which flavonols interact with the
BP (Table 1). On release into the bloodstream by the RAAS may vary, and ongoing research aims to explore
endothelium, NO either binds to hemoglobin or diffuses these pathways in detail.
into smooth muscles. 78 An important independent risk factor for cardiovascular
Within smooth muscles, NO binds and activates events, such as coronary heart disease and stroke, is high
guanylyl cyclase, initiating the cGMP-protein kinase G BP. Many different pathways influence hypertension, a
cascade pathway. This cascade involves a series of chemical complex illness that is frequently necessary but has no
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reactions within the effector cell, culminating in smooth clear etiology. Despite the availability of numerous
muscle relaxation. Activation of the cGMP-protein kinase antihypertensive drugs, many patients still struggle
G cascade leads to several mechanisms that enhance with suboptimal BP control, posing a heightened risk
smooth muscle relaxation through elevated levels of of cardiovascular complications. Consequently, efforts
cGMP, including the inhibition of Ca uptake within cells, to reduce hypertension prevalence have focused on
2+
+
activation of K channels resulting in hyperpolarization, non-pharmacologic approaches, with dietary measures
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and subsequent vasodilation. Another mechanism emerging as effective strategies. Increasing fruit and
involves the phosphorylation of myosin light chains by vegetable intake, aligned with guidelines for modulating
activated cGMP-dependent kinase, further reducing hypertension, is particularly noteworthy. Apart from
vasoconstriction in vascular smooth muscles. 87 popular dietary strategies such as the Mediterranean diet
and the dietary approaches to stop hypertension diet,
Vasodilation, achieved through these mechanisms, widens flavonoids and dietary sources containing flavonoids have
the blood vessel lumen, facilitating increased blood flow and garnered interest due to their potential to decrease BP. 92
reducing hypertension. Flavones exhibit antihypertensive
activity by targeting the cGMP protein kinase G cascade. Evidence from observational studies, clinical trials, and
They activate the cGMP protein kinase A cascade, leading meta-analyses supports the positive impact of flavonoid-
to excessive synthesis and secretion of endothelial NO. This, rich foods on hypertension. Diets rich in vegetables and
in turn, induces vasodilation by modulating Ca and K fruits, fruit juices, berries, green, and black tea, as well
+
2+
ion levels, promoting hyperpolarization of smooth muscles as cocoa and dark chocolate, have been associated with
adjacent to the endothelium. 55 reduced BP. Notably, cocoa may exhibit superiority
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Flavonols, such as kaempferol and quercetin, among flavonoid sources in effectively lowering BP. 94
demonstrate their antihypertensive effects through the Research suggests that increased NO bioavailability,
modulation of the RAAS. This regulatory system plays in conjunction with antioxidant and anti-inflammatory

Volume 3 Issue 2 (2024) 7 doi: 10.36922/gtm.2458