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Global Translational Medicine Impact of flavonoids on vascular health

reduction in ROS, and direct renal effects. However, these obesity, smoking, advancing age, hypertension, familial
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mechanisms remain subjects of ongoing research. predisposition, endothelial dysfunction, suboptimal
In summary, research on humans and animals dietary patterns, insulin resistance, and diabetes. 116
has shown that a number of flavonoids, most notably While mortality rates attributable to ischemic heart
epicatechin and quercetin, have antihypertensive effects. disease or stroke have markedly diminished in developed
However, it is noteworthy that these benefits are primarily nations since 1990s, ischemic heart disease persists as
observed when BP is elevated. Therefore, flavonoids could the foremost cause of premature mortality among adults.
be viewed as an adjunct to antihypertensive medication. Consequently, atherosclerosis stands out as the most
Nevertheless, more investigation is needed to determine prevalent and, consequently, the most hazardous form
the precise pathways underlying the BP-lowering effects of arteriosclerosis. As mentioned earlier, the onset and
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and the therapeutic significance of each flavonoid molecule. development of atherosclerosis involve multiple processes.
5. Flavonoids and atherosclerosis Flavonoids exhibit a wide range of mechanisms of action,
including the inhibition and activation of enzymes, the
Under specific conditions, the walls of blood vessels control of gene and protein expression, and functions such
may undergo a process of filling and thickening due to as cytotoxic, anti-ulcerogenic, anti-microbial, antiviral,
the accumulation of substances carried by the blood or anti-neoplastic, hepatoprotective, antihypertensive, lipid-
produced within the vessel itself. These substances include lowering, antiplatelet, and anti-inflammatory effects.
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cholesterol, fatty acids, calcium, and fibrin, as well as various Due to these diverse actions, flavonoids can influence the
cells such as red blood cells, platelets, smooth muscle course of the disease, preventing or reducing its severity,
cells, fibroblasts, and macrophages. This process, termed whether in vitro, in vivo, or as observed in clinical trials.
arteriosclerosis, results in the hardening, stiffening, and
narrowing of the vessel at the affected site, thereby reducing Historically, doubts existed about the benefits of
the blood supply to the surrounding tissue. Factors such flavonoid intake in preventing atherosclerosis due to
contradictory results, variations in doses used in studies,
as obesity, an unhealthy diet, or lipid metabolism issues and a lack of in vivo data. While some challenges
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can contribute to the accumulation of cholesterol, fatty persist, such as the non-standardization of compounds
substances (triglycerides and LDL), fibrin, calcium, and and doses, and the need for more clinical studies with
extracellular matrix components within the vessel wall. In single flavonoids, accumulated results have rendered these
response to these accumulations, macrophages infiltrate concerns outdated. Clear evidence now exists that several
the vessel walls and phagocytize oxidized LDL (ox-LDL) flavonoids can prevent and mitigate atherosclerosis,
due to heightened levels of oxidative stress, transforming demonstrated in both in vitro cultures and in vivo animal
into “foam cells” due to the presence of fat droplets within models. As an illustration, quercetin, one of the extensively
them. This infiltration gives rise to the characteristic investigated flavonoids, has demonstrated efficacy in
fatty streaks observed in atherosclerotic vessels. The mitigating the advancement of atherosclerosis. In a recent
amalgamation of substances from the blood and vessels, investigation utilizing apolipoprotein E deficient (ApoE )
-/-
combined with infiltrated vascular cells, forms a structure mice, a common animal model for atherosclerosis research,
known as a “plaque,” which significantly alters the vessel the administration of a diet enriched with 0.1% (w/w)
wall, making it more rigid and narrower. This alteration quercetin over a duration of 20 weeks effectively suppressed
results in a specific type of arteriosclerosis known as dendritic cell activation and the inflammatory response,
atherosclerosis. 115 notably impeding the progression of atherosclerotic
Over time, atherosclerotic plaques can grow to the extent pathology observed in untreated counterparts. Moreover,
of creating a thrombus capable of obstructing the vessel this intervention yielded a notable 30% decrease in
and causing tissue ischemia. Alternatively, the plaque may atherosclerotic lesions within the aortae. In a subsequent
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become unstable, rupture, and release fragments, leading to in vitro study, the observed effects were attributed to
emboli that could cause an embolism by blocking a vessel quercetin’s ability to downregulate dendritic cell activation
anywhere in the body. Consequently, atherosclerosis is a by increasing disabled 2 (Dab2) protein expression,
chronic disease that develops silently over many years until thereby inhibiting the pivotal NF-κB inflammatory
sudden clinical manifestations appear, including ischemic pathway. Furthermore, the O-methylated flavone nobiletin
heart disease, stroke, and peripheral arterial disease. exhibited its capacity to inhibit the NF-κB inflammatory
Established risk factors implicated in the pathogenesis of pathway in human umbilical endothelial cells (HUVECs),
atherosclerosis include chronic inflammation, oxidative indicating potential antiatherogenic effects. Earlier
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stress, elevated levels of blood cholesterol and lipids, research had already indicated that quercetin surpassed

Volume 3 Issue 2 (2024) 11 doi: 10.36922/gtm.2458