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Global Translational Medicine Impact of flavonoids on vascular health

Table 1. (Continued)
Study Details and findings of the study
Ali et al. 85 (i) This study investigated the antihypertensive properties of quercetin and its underlying mechanisms in angiotensin II (Ang
II)-induced hypertension.
(ii) In Ang II-infused C57BL/6 mice, quercetin treatment significantly reduced the increase in blood pressure, pulse wave
velocity, and aortic thickness of the abdominal aorta. RNA sequencing revealed that quercetin treatment reversed 464
differentially expressed transcripts in the abdominal aorta of Ang II-infused mice.
(iii) Further analysis identified common pathways affected by quercetin treatment, including cell cycle and p53 pathways,
which play crucial roles in regulating vascular function and proliferation. Immunohistochemistry confirmed that quercetin
decreased the expression of proliferating cell nuclear antigen, cyclin-dependent kinase-4 (CDK4), and cyclin D1 while
increasing the expression of p53 and p21 in abdominal aortic tissues.
(iv) In vitro studies with vascular smooth muscle cells (VSMCs) showed that quercetin treatment decreased cell viability, arrested
cell cycle progression at the G0/G1 phase, and upregulated the expression of p53 and p21 proteins. In addition, quercetin
downregulated the expression of cell cycle-related markers CDK4 and cyclin D1 in Ang II-stimulated VSMCs.
Abbreviation: TNF-α: Tumor necrosis factor-alpha.

qualities, may be the primary ways that diets high in include Zucker rats that are obese or animals who are fed a
flavonoids reduce hypertension. Notably, similar fat- and sugar-rich diet. The range of chronic dosages often
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antihypertensive outcomes have been observed in pre- utilized in these studies is 2 – 300 mg/kg/day, with the most
clinical and clinical studies when products enriched with regularly used dose being 10 mg/kg/day. 98
flavonoids or flavonoid extracts were administered. 30,93,95 Carresi et al. examined the effects of a polyphenol-rich
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However, contrasting results have emerged, especially fraction of bergamot (BPF) on renovascular hypertension
in trials related to red wine, tea, soy, and chocolate. The (RVH) and associated reno-cardiac diseases using a rat
differences in study designs, participant heterogeneity, model. They induced hypertension in adult male Wistar
dosage differences, varying flavonoid concentration rats through unilateral renal artery ligation and treatment
and bioavailability, and the inclusion of alcohol, high- with DOCA and 1% NaCl water. The rats were divided
calorie food (sugar and saturated fat), and caffeine in into groups receiving DOCA and NaCl water treated
certain products can all contribute to the variance. These with BPF gavage treatment or subcutaneous injection
variations highlight the need to investigate individual pure of vehicle treatment (control). Results revealed that rats
flavonoids. subjected to renal artery ligation and DOCA treatment
The capacity of the main dietary flavonoids from experienced increased mean arterial BP, resistive index of
five regularly ingested subgroups—flavonols and contralateral renal artery flow, and kidney volume, along
anthocyanins—to lessen or ameliorate an increase in BP with dysfunction in cardiac tissue strain and dyssynchrony
is outlined in a thorough review by Clark et al. All of in cardiac wall motion. These rats also exhibited elevated
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these flavonoids have shown antihypertensive benefits in levels of pro-inflammatory cytokines and chemokines and
a variety of animal models and clinical trials; however, we increased expression of neutrophil gelatinase-associated
shall concentrate on quercetin and epicatechin due to their lipocalin (NGAL) in the ligated kidney. Treatment with BPF
exceptional capacities in consistently lowering BP. prevented the increase in BP, protected the contralateral
Particularly, quercetin has demonstrated antihypertensive kidney volume, and ameliorated cardiac tissue strain
benefits in widely used preclinical models of hypertension. dysfunction and dyssynchrony. Furthermore, BPF reduced
Initial reports on its effects were conducted on SHR, a model circulating levels of pro-inflammatory cytokines and
mirroring human hypertension. Further investigations chemokines and restored NGAL levels in the kidney.
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have confirmed and extended these results in various In human epidemiological research, a negative
hypertensive rodent models, such as Goldblatt rats with correlation has been observed between dietary quercetin
two kidneys and one clip, rats with constricted aortas, rats intake and hypertension. Several clinical investigations
treated with Nω-nitroL-arginine methyl ester (L-NAME), have demonstrated a drop in BP following the
rats infused with Ang II, rats with hypertension induced consumption of pure quercetin. For instance, Edwards et
from deoxycorticosterone acetate (DOCA)-salt, rats with al. demonstrated BP-lowering effects without systemic
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hypertension induced from sensitivity to Dahl salt, and rats markers of oxidative stress reduction in patients with
with hypertension induced from sodium chloride (NaCl). stage 1 hypertension. In addition, Egert et al. revealed
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The effectiveness of quercetin in lowering the increased BP that quercetin lowered BP in overweight individuals
has also been shown in metabolic syndrome models, which with a high CVD risk profile and in overweight-obese

Volume 3 Issue 2 (2024) 9 doi: 10.36922/gtm.2458