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Global Translational Medicine Impact of flavonoids on vascular health

oxidation of LDL and the production of foam cells. In a miR-122, which are important regulators of liver lipid
study conducted on RAW264.7 macrophages, researchers metabolism. Furthermore, in RAW264.7 macrophages
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observed a significant impact of chrysin treatment on challenged with lipopolysaccharide, quercetin, and
cellular cholesterol levels and its transport mediated by isorhamnetin downregulated the proinflammatory miR-
high-density lipoprotein (HDL). RAW264.7 macrophages 155, although the metabolite Q3GA did not show this
are a commonly used cell line for studying macrophage impact. 138
biology and lipid metabolism. On exposure to varying Two recently identified anti-atherosclerotic actions of
concentrations of chrysin, the researchers noted a dose- flavonoids — the modulation of gut microbiota activity
dependent increase in the export of cholesterol mediated and miRNA activity — have been connected in a significant
by HDL. Furthermore, the study revealed a concurrent study. Similar to chrysin, protocatechuic acid, a metabolite
decrease in intracellular cholesterol levels following of the anthocyanin cyanidin-3-O-β-glucoside generated
chrysin treatment. This reduction in cellular cholesterol by gut microbiota action, has shown antiatherogenic
content indicates that chrysin effectively decreases properties in ApoE mice by reversing cholesterol transit
-/-
the amount of cholesterol stored within macrophages. and promoting its efflux from macrophages. 139,140
Importantly, the magnitude of this reduction was
comparable to that achieved with lovastatin, a well-known A unique theory about the pathophysiology of
hypocholesterolemic drug commonly prescribed for atherosclerosis has gained popularity recently, speculating
lowering cholesterol levels in patients at risk of CVD. 130 that established risk factors may serve as a potentiator for
an underlying dietary element. Trimethylamine N-oxide
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One promising therapeutic avenue for the prevention (TMAO) is the implicated factor. It is formed from
and treatment of atherosclerosis is the impact of flavonoids trimethylamine (TMA), which is present in meat, milk, and
on reverse cholesterol transport. A recently elucidated fish, among other food products obtained from animals.
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mechanism through which certain flavonoids operate These TMAs are released by gut microbial metabolism,
involves the augmentation of paraoxonase (PON) proteins’ which is crucial for the onset of disease. Following
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activity or expression. PONs are enzymes associated with absorption, TMA is transported to the liver, where it is
anti-inflammatory, antioxidative, and antiatherogenic oxidized into the harmful TMAO by flavin-containing
properties. Research suggests that in cultured mouse mono-oxygenase 3 (FMO3). Studies linking TMAO to the
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macrophages, quercetin and isorhamnetin can upregulate etiology of metabolic and CVDs, such as atherosclerosis, are
PON2 gene expression. Nevertheless, quercetin failed becoming increasingly numerous. Based on the TMAO
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to elicit the same effects in humans, most likely due to hypothesis, only the effects of phloretin, a flavonoid, have
conjugation with glucuronic acid, which reduced PON2- been studied in a mouse model of atherosclerosis thus
inducing activity, demonstrating the variability of the far. Mice were fed a diet rich in choline along with 100,
actions of flavonoids and their metabolites. Examining 200, and 400 mg/kg/day of dihydrochalcone phloretin
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quercetin’s impact on PON1 gene expression and activity for 10 weeks. This dietary intervention resulted in signs
revealed similar results. In addition, by raising PON1 of endothelial dysfunction, elevated oxidative stress,
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activity, shielding LDL from oxidation, and reducing hyperglycemia, and hyperlipidemia. However, treatment
lipid peroxidation, quercetin showed anti-atherosclerotic with phenyleptin mitigated these harmful consequences,
benefits in a rat model exposed to oxidative damage leading to a limitation of weight gain, enhancement of the
induced by mercuric chloride. While not as potent, lipid profile, and maintenance of endothelial and hepatic
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catechin exhibited similar effects. Recent research has function. 144
further investigated the effect of flavonoids on PON activity In a rigorously conducted double-blind crossover
in humans using extracts and enriched meals, confirming study involving 49 healthy male subjects characterized by
the compounds’ ability to increase PON expression or the APOE genotype, quercetin emerged as a compound
activity. 20
manifesting discernible antiatherogenic effects. The study
MicroRNAs represent a burgeoning field of research spanned a duration of eight weeks during which participants
for CVD. These small non-coding RNAs regulate gene were administered a daily dosage of 150 mg of quercetin.
expression and protein expression, playing a pivotal This intervention yielded notable reductions in both waist
role in various vascular processes and being altered in circumference and postprandial systolic BP across the
pathological states such as hypertension, atherosclerosis, entire cohort. The investigational outcomes further revealed
and diabetes. For example, in dyslipidemic obese rats, a salient decline in postprandial triacylglycerol levels,
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long-term proanthocyanidin treatment reversed elevated coupled with a concurrent elevation in HDL-cholesterol
levels of miR-33a, miR-21, miR-122, miR-3064-5p, and relative to the placebo group. However, despite these

Volume 3 Issue 2 (2024) 13 doi: 10.36922/gtm.2458