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Global Translational Medicine Impact of flavonoids on vascular health

other flavonoids in efficacy for slowing atherosclerosis inflammatory indicators, enhances endothelial function,
progression and reducing plaque size. These findings and lowers high serum lipid levels. It also inhibits the
were associated with enhanced endothelial function, formation of macrophage-derived foam cells. 124
characterized by increased vascular endothelial eNOS When dyslipidemia was examined for its effects on
activity, and modulation of oxidative stress status, cerebral artery flow and structure, catechin was shown
evidenced by elevated heme oxygenase-1 protein levels and to shield atherosclerotic mice from alterations in the
nitrate excretion. In addition, a decrease in inflammatory compliance and structure of the arterial wall. This protective
markers was noted, including reduced levels of vascular strategy was associated with improved endothelial function,
superoxide anion (O ) and leukotriene B4, as well as normalization of pro-metalloproteinase-9 (MMP-9) activity,
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decreased aortic F2-isoprostane and plasma P-selectin and a decrease in ROS produced as a result of oxidative
concentrations. Moreover, in the same investigation, the stress. Different flavonoids show similar effects, albeit
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dimeric catechin theaflavin demonstrated the potential to with varying levels of intensity, suggesting different levels of
diminish the size of atherosclerotic lesions and improve efficacy against atherosclerosis. Supporting this idea, male
some of these parameters, albeit with lesser potency. 121 C57BL/6 mice that received a 0.6% w/w luteolin supplement
However, these results are not the sole evidence for 3 weeks showed significant reductions in TNF-α-
supporting the in vivo antiatherogenic properties of induced vascular inflammation. This supplementation
quercetin. In a similar ApoE mouse model, this time fed reduced serum levels of chemokines, such as IL-8, ICAM-1,
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a high-fat diet for 24 weeks, quercetin supplementation and the mouse homolog of human monocyte chemotactic
reduced the atherosclerotic plaque area in the aorta, protein-1 (MCP-1). Luteolin decreased VCAM-1 and
particularly by 27.7% with the high dose of quercetin, monocyte-derived macrophages in the aorta in comparison
closely aligning with the 30% reduction observed in the to untreated animals, due to its ability to impede monocyte
aforementioned study. Furthermore, this intervention adherence to the endothelium, a critical stage in the
resulted in a dose-dependent decrease in macrophage subsequent development of foam cells in atherosclerotic
infiltration within the atherosclerotic lesion, reduced plaques. Further in vitro tests revealed that luteolin exerted
accumulation of ox-LDL, diminished systemic oxidative comparable effects by inhibiting the NF-κB pathway and
stress, and suppressed expression of NADPH oxidase thus decreasing TNF-α-stimulated production of MCP-1
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subunits p47phox and p67phox in the aorta compared and adhesion molecules ICAM-1 and VCAM-1.
to untreated mice. In addition, in vitro experiments In high-fat-fed mice, naringenin, a flavonoid, showed
demonstrated that quercetin could impede the promise in suppressing macrophage infiltration into
translocation of p47phox to the cell membrane and adipose tissue during a brief 14-day treatment at a dose of
mitigate NADPH oxidase activation induced by ox-LDL in 100 mg/kg/day. This effect was linked to MCP-1 inhibition,
mouse peritoneal macrophages. Remarkably, alongside similar to luteolin. Compared to untreated high-fat-
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quercetin’s systemic antiatherogenic characteristics, its fed mice, naringenin-treated high-fat-fed mice showed
glucuronides, notably quercetin-3-glucuronide (Q3GA), improvements in body weight, blood glucose, or lipid
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the principal quercetin metabolite detected in human profile. Another flavonoid, baicalin, showed inhibitory
blood, selectively accumulate within atherosclerotic effects on MCP-1, VCAM-1, and IL-6 in the kidneys of
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lesions in the human aorta, predominantly within foam high-cholesterol-fed ApoE mice when administered at a
cells originating from macrophages. Even subsequent to dose of 100 mg/kg/day for 12 weeks, thereby maintaining
deconjugation and conversion back to quercetin aglycone, renal function. 128
these metabolites maintain their activity. 123 Flavonoids are instrumental in shielding the
According to a recent meta-analysis, of the 18 endothelium from oxidative damage caused by ox-LDL. In
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flavonoids examined, quercetin and its metabolites were a study, pretreatment with EGCG shielded HUVECs from
the most effective in reducing aortic atherosclerotic lesions oxidative harm induced by ox-LDL. This protection was
in the ApoE mouse model. While not as well researched evidenced by heightened expression of eNOS, improved
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as quercetin, other flavonoids also show significant endothelial function, prevention of iNOS induction, and
antiatherosclerotic qualities, primarily by blocking other reduced expression of NADPH oxidase subunits. Moreover,
pro-inflammatory mediators and pathways. For example, EGCG pretreatment reversed the ox-LDL-induced
dihydromyricetin has demonstrated antiatherogenic alterations in the Jagged-1/Notch pathway, indicating its
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benefits in the atherosclerotic model using LDL receptor- pivotal role in the observed protective effects.
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deficient (LDLr ) mice fed a high-fat diet. Like quercetin, Flavonoids aid in the removal of cholesterol from
it decreases oxidative stress, ox-LDL generation, and macrophages and also play a part in inhibiting the

Volume 3 Issue 2 (2024) 12 doi: 10.36922/gtm.2458