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Global Translational Medicine Impact of flavonoids on vascular health

available substituting groups, with prevalent occurrences A growing body of research relates diets high in flavonoids
in the peels of diverse berries and currants. Beyond their to improved vascular health, influencing endothelium-
aesthetic contribution, anthocyanins positively influence dependent vasorelaxation and NO bioavailability in both
the cardiovascular system by inducing endothelium- physiological and pathological settings. Nevertheless, little
dependent vasodilation. Moreover, they exhibit the is known about the specific processes by which flavonoids
capacity to lower BP in individuals with hypertension. 43 enhance endothelium functions. Numerous molecular
pathways, including endothelium- and NO-dependent
2.6. Isoflavones relaxations, as well as antioxidant, anti-inflammatory, and

Abundant in leguminous plants, particularly soybeans, antiproliferative qualities, have been postulated by research
lentils, peas, and even certain microbes, isoflavones constitute conducted in both human and animal models. 52,53
a significant class of flavonoids. Notably, soy isoflavones In isolated arteries, flavonoids exhibit different
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share structural similarities with mammalian estrogens, vasodilator actions, varying in strength. Different
rendering them estrogen receptor agonists. Among the mechanisms underlie these relaxing actions, particularly
well-studied examples in this category are daidzein and with regard to the function of NO and endothelium.
genistein. Enhanced consumption of isoflavones leads Certain flavonoids, such as myricetin and epigallocatechin
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to the conversion of endogenous estrogens into their gallate (EGCG), increase the vasoconstrictor prostanoids
protective derivatives. Genistein, for instance, demonstrates generated from cyclooxygenase (COX), which might
an antihypertensive effect, while daidzein plays a role in induce an endothelium-dependent contractile response. 54
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reducing oxidative stress-induced damage and low-density
lipoprotein (LDL) oxidation, concurrently promoting the Certain flavonoids, such as quercetin and kaempferol,
production of prostaglandins (PGIs) and NO. 47 promote an endothelium-independent vasodilation
mechanism in isolated arteries, contributing to a reduction
3. Flavonoids and vascular function in arterial pressure in experimental models. Interestingly,
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Numerous vasoactive compounds are released by compared to conductance vessels, the effects of these
endothelial cells, and these molecules are essential for direct vasodilators are more noticeable in coronary and
2+
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controlling vascular shape and function in both healthy resistance arteries. The suppression of intracellular Ca
and pathological settings. A broad class of compounds release from the endoplasmic reticulum (ER), decrease in
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2+
known as flavonoids interacts with a variety of targets and Ca influx into VSMCs, and activation of ATP-sensitive
has a range of biological effects, suggesting that they may potassium (KATP) channels are responsible for the
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be used to treat a wide range of illnesses. Although the endothelium-independent relaxant responses.
antioxidant effect was thought to be the main mechanism Flavonoids contribute to improving endothelial
of action for flavonoids and polyphenols in the 1980s dysfunction associated with cardiovascular diseases
and 90s, new research has provided a deeper insight. It is (CVDs) through increased endothelium- and
now known that direct interactions with protein targets— NO-dependent relaxations. By heightening endothelium-
particularly kinases—can modify signaling cascades. derived relaxing factors, such as increased NO and H O
2
2
Moreover, a plausible reason for flavonoids’ beneficial release, they induce acute endothelium-dependent
effects on human health is their pro-oxidant activity, vasodilation. Reactive oxygen species (ROS) released by
which activates antioxidant defense systems such as the endothelial cells drive this prooxidant process, which can
expression of antioxidant enzymes or the upregulation of be blocked by superoxide dismutase (SOD) and catalase
endogenous antioxidant pathways. 49 (CAT). 58

Despite their interactions with multiple targets, The availability of NO is the main mechanism
flavonoids are notably safe, possibly due to their underpinning the endothelium-dependent vasodilation
longstanding presence in the mammalian diet, suggesting caused by flavonoids. By upregulating the expression and
evolved mechanisms to mitigate toxicity. NO is essential activity of endothelial NO synthase (eNOS) and reducing
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for preserving vascular homeostasis due to its integral roles NO degradation, flavonoids regulate the generation of
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in platelet aggregation, blood flow, vascular tone, and the NO. Flavonoids like red wine polyphenols and delphinidin
regulation of VSMC proliferation. Endothelial dysfunction, enhance eNOS mRNA expression in endothelial cells.
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which is characterized by decreased NO bioavailability, They modulate eNOS activity through a Ca /calmodulin-
2+
elevated oxidative stress, impaired endothelium-dependent dependent pathway, elevating intracellular Ca levels,
2+
vasodilation, and a prothrombotic, pro-inflammatory or through a Ca -independent mechanism through
2+
state of the vascular wall, is significantly influenced by phosphatidylinositol 3-kinase (PI3-K)/protein kinase B
disruptions in NO signaling pathways. 51 (Akt)-dependent eNOS phosphorylation at the activation
Volume 3 Issue 2 (2024) 4 doi: 10.36922/gtm.2458