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Quercetin and blood pressure

Quercetin and blood pressure

Table 3 Publication bias in Qufrcetin meta-analysis of Quercetin and blood pressure. Adult Recommended adult dosages pressute quercetin vary depending on the condition being treated. Funnel plots revealed no obvious publication bias Figure 4. Pérez-Vizcaíno F, Ibarra M, Cogolludo AL, Duarte J, Zaragozá-Arnáez F, et al.

Quercetin and blood pressure -

All other drugs were from Sigma Tres Cantos, Madrid, Spain. Results are expressed as the mean ± SEM and n describes the number of measurements made i. Differences between experimental groups were treated using unpaired Student's t-test or, for multiple comparisons, using one-way analysis of variance followed by a Dunnett's post hoc test.

SHR showed a basal MBP of ±5 mm Hg and HR of ±14 bpm. progressively reduced mean blood pressure MBP in SHR, while Q3'S was without effect. This hypotensive effect induced by both metabolites was statistically significant after 1 and 2 h, respectively, of the metabolite injection.

The maximum effects observed at 3 h were No significant changes in heart rate HR were observed with any metabolite Figure 2B. Q3GA also decreases MBP at low concentrations 0.

Results are means ± SEM of 4—6 experiments. Moreover, free quercetin aglycone and I3GA was detected in plasma after Q3GA injection. A HPLC chromatograms recorded at nm of plasma samples taken at 1 min.

B Time-concentration relationship. Results are means ± SEM of 4 experiments. Phenylephrine induced a maximal contractile effect in mesenteric vessels from SHR of When mesenteric arteries from SHR were incubated with the aglycones quercetin or isorhamnetin for 30 min a significant concentration-dependent decrease in the vasoconstrictor response to phenylephrine was observed Figure 4 while Q3GA at this time had no effect Figure 5A.

However, when the incubation of 25 µM Q3GA was prolonged to 1 and 2 hours a significant reduction in the vasoconstriction induced by phenylephrine was detected Figure 5B and 5C.

Control is treated with vehicle DMSO. Results are means ± SEM of 4—8 experiments. To explore the possible role of deconjugation of Q3GA on the observed effects a specific inhibitor of beta-glucuronidase SAL was used, which was administered i. during the 3 days before the blood pressure recordings.

Interestingly, the hypotensive effect of Q3GA was abolished in SHR treated with SAL Figure 6A. We confirmed the inhibitory glucuronidase activity of SAL 1 mM in homogenates from the mesenteric bed in in vitro conditions, by incubating during 1 h and measuring glucuronidase activity Figure 6C.

We also found that the inhibitory effects of Q3GA in the contractile response induced by phenylephrine were suppressed when mesenteric arteries were incubated with SAL Figure 6D , but not those of quercetin Figure 6E. Panel C shows the bands of β-glucuronidase expression by Western blot and the β-glucuronidase activity and its inhibition by SAL 1 mM in vascular bed homogenates means ± SEM of 8 experiments.

D Effects of Q3GA 25 µM on the contractile responses to phenylephrine in mesenteric arteries after min in the presence of SAL 1 mM means ± SEM of 5 experiments. E Effects of quercetin 25 µM on the contractile responses to phenylephrine in mesenteric arteries after 30 min in the presence of SAL 1 mM means ± SEM of 5 experiments.

The above results prompted us to analyze whether deconjugation was also required for the antihypertensive effect of orally administered quercetin. These reductions were significant, as compared to vehicle, after 2.

Importantly, when SHR were treated with SAL, oral quercetin was unable to induce changes in both MBP and HR Figure 7C, 7D. However, SAL was unable to modify the in vitro effect of quercetin on the contractile response to phenylephrine in isolated mesenteric arteries.

Fruit and vegetable consumption is associated with a decrease in blood pressure, which is an important cardiovascular risk factor [30]. Quercetin, the most important dietary flavonol, present in multiple fruits and vegetables, reduces blood pressure in hypertensive animals and human after chronic consumption [9] , [13] , [31] — [37].

Herein, we show for the first time that the conjugated derivatives Q3GA and I3GA can exert antihypertensive effects when administered intravenously. As previously reported Q3GA had no acute effect in vitro at 30 min , however it developed with more prolonged incubations. Both the in vitro and the in vivo effects were prevented by the β-glucuronidase inhibitor SAL.

Taken together these data strongly suggest that deconjugation is required for the effect of quercetin metabolites. Both human and rat tissues, except for the cells lining the intestine tract, are exposed to quercetin via the blood.

Because glucuronidated and sulfated compounds are the only detectable metabolites, it is suggested that conjugated metabolites must play a decisive role in the possible beneficial effects [38]. Our results support this hypothesis, because we showed that Q3GA and I3GA, the main plasma metabolites of quercetin exerted an antihypertensive effect.

Doses of Q3GA as low as 0. In contrast, Q3'S was without effect. Herein, we show that both Q3GA and I3GA metabolites show a similar effect. Previous published papers from other groups [15] — [18] , the concentrations of methylated forms of quercetin are in the same range or higher than non methylated ones in rats and humans supplemented with quercetin, suggesting that both forms may contribute to the antihypertensive effect.

When we analyzed the time course of the antihypertensive effect and compared it to the plasma concentrations of Q3GA we found a clear dissociation Fig. However, Q3GA rapidly disappeared from the plasma, indicating that the two modes of administration result in a completely different pharmacokinetic profile.

The fast decay of Q3GA concentration in plasma is not compatible with renal excretion, suggesting that Q3GA is metabolized, accumulated in tissues or both. In a recent in vitro study [24] , the perfusion of Q3GA through the rat mesenteric vascular bed resulted in a partial accumulation of Q3GA in the tissue and a progressive process of deconjugation.

The resulting aglycone was partly found in the extracellular buffer and mostly retained intracellularly. The beta-glucuronidase inhibitor SAL increased the tissue Q3GA and reduced the aglycone. Deconjugation by beta-glucuronidase is expected to occur intracellularly because this enzyme is located in the lysosomes and the microsomal fraction.

Therefore, the aglycone is formed within the vessel and probably in the cytosol of smooth muscle cells where it is expected to interact with its targets to exert vascular smooth muscle relaxation.

The most plausible targets for this effect include the protein kinases involved in the regulation of myosin-actin interactions including protein kinase C, myosin light chain kinase or Rho kinase and possibly potassium channels [8] , [9] , [40] , [41].

Quercetin aglycone released to the plasma is likely to be rapidly re-conjugated in the liver explaining its low levels. The vasorelaxant effects of quercetin and related metabolites have been widely assessed in vitro in aorta and perfused mesenteric bed [7] , [8] , [42]. Increased alpha-adrenergic response in small mesenteric arteries has been involved in increased blood pressure in SHR [43] , [44].

As expected, both quercetin and isorhamnetin incubated during 30 min, inhibited the contractile response induced by the alpha-adrenergic receptor agonist phenylephrine.

In the same experimental conditions, Q3GA did not modify this response. These results are consistent with previous data showing that conjugation of flavonoids results in a decreased biological activity [45] , [46] and that conjugated metabolites have no direct vasorelaxant effect in isolated rat aorta at physiological concentrations [21].

However, when small mesenteric arteries were incubated for 1 or 2 h with Q3GA, at 25 µM, the vasoconstriction induced by phenylephrine was significantly reduced, suggesting that quercetin accumulates in this vascular bed and it is responsible of the reduced vascular tone.

Deconjugation of the glucuronide metabolites of the flavonoids by increased β-glucuronidase activity at the site of inflammation has been suggested as a plausible mechanism for the protective effects of flavonoids in vivo [23] , [48].

Accordingly, the release of β-glucuronidase is considered an index of lysosomal membrane integrity [49]. In fact, mesenteric bed from SHR expresses β-glucuronidase and its activity was significantly inhibited by SAL, a specific inhibitor.

Vascular tissues from SHR showed increased expression of proinflammatory markers, altered endothelial function, and increased macrophage infiltration than normotensive animals [50] , [51] , which could facilitate metabolite accumulation and deconjugation in this inflamed tissue.

In our experiments, the antihypertensive effect of Q3GA was abolished by β-glucuronidase inhibition, which suggests that this effect requires β-glucuronidase-mediated deconjugation. Moreover, the inhibitory effect in the contractile response to phenylephrine in mesenteric arteries induced by Q3GA was also suppressed by SAL, showing that Q3GA requires deconjugation to exert this inhibitory effect.

Given the role of β-glucuronidase in the effects of Q3GA we aimed to analyze whether it was also relevant for the antihypertensive effect of quercetin. Surprisingly, despite several chronic studies, to our knowledge the effects of acute oral quercetin administration on blood pressure in hypertensive animals had not been studied.

We found a slow developing but long lasting antihypertensive effect. Remarkably, the effects of oral quercetin were also abolished by β-glucuronidase inhibition with SAL. However, as expected, the in vitro effects of quercetin were unaffected by SAL.

Thus, our data suggest that the biological activity of quercetin is dependent on the conjugation-deconjugation processes. Therefore, glucuronidation may protect quercetin from its metabolism via other pathways and help to carry the flavonoid to the tissues where the free aglycone is released [52].

Our data also suggest that polymorphisms of UDP-glucuronosyltransferases encoded by the UGT1 and UGT2 loci , which are common in humans [53] and changes in the β-glucuronidase activity, might result in a variable response to quercetin.

In conclusion, we show that glucuronides of quercetin and its methylated metabolite isorhamnetin are involved in the antihypertensive response of oral quercetin, which might be related, at least in part, by the inhibitory effect in the α-adrenergic-induced hypercontractile response in resistance arteries.

Quercetin could be initially inactivated by a conjugation metabolism during absorption and then safely be delivered to inflamed arterial wall, and the recruited metabolites are incorporated and converted to the aglycone in vascular smooth muscle cells and exert the inhibitory activity on vascular tone.

These results are in agreement with the hypothesis that flavonoid glucuronides appear to serve as plasma transport metabolites to target cells rather than solely as excretion.

Conceived and designed the experiments: FP-V JD. Performed the experiments: PG IR-G SG-M MD RJ CM. Analyzed the data: RJ FV JT CS-B JD. Wrote the paper: FP-V JD. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.

Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract Background Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. Conclusions Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues.

Calixto, Universidad Federal de Santa Catarina, Brazil Received: November 28, ; Accepted: February 2, ; Published: March 12, Copyright: © Galindo et al. Introduction Flavonoids are polyphenolic compounds that occur ubiquitously in plants and are consumed in the form of fruits, vegetables, nuts and derived products such as wine and chocolate.

Download: PPT. Figure 1. Materials and Methods Animals All the experiments were performed in accordance with Institutional Guidelines for the ethical care of animals, and ethic committee of the University of Granada approved this study ref.

Blood pressure measurement Direct blood pressure was measured in conscious SHR. Analysis of quercetin metabolites in rat plasma Blood was collected into heparinized tubes and centrifuged. Vascular reactivity in vitro SHR were stunned and killed by cervical dislocation.

β-glucuronidase activity β-glucuronidase activity was measured by a colorimetric analysis using phenolphthalein mono-β-glucuronide as the substrate [22]. Materials Q3GA was isolated from green bean pods and stored as described [27]. Statistical analysis Results are expressed as the mean ± SEM and n describes the number of measurements made i.

Since quercetin affects the liver, concomitant use with medications that are changed by the liver may alter how the body metabolizes these medications. Speak with your physician.

Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. Boots AW, Li H, Schins RP, Duffin R, Heemskerk JW, Bast A, Haenen GR. The quercetin paradox. Toxicol Appl Pharmacol. Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP.

Oxidative damage and protection of the RPE. Prog Retin Eye Res. Chan MM, Mattiacci JA, Hwang HS, Shah A, Fong D. Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway.

Bio Pharm. Chuang CC, Martinez K, Xie G, et al. Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-{alpha}-mediated inflammation and insulin resistance in primary human adipocytes.

Am J Clin Nutr. Dajas F. Life or death: neuroprotective and anticancer effects of quercetin. J Ethnopharmacol. Dower JI, Geleijnse JM, Gijsbers L, Zock PL, Kromhout D, Hollman PC. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cariometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.

Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr. Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a doule-blinded, placebo-controlled cross-over study.

Br J Nutr. Gates MA, Tworoger SS, Hecht JL, De Vivo I, Rosner B, Hankinson SE. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer.

Int J Cancer. Giuliani C, Noguchi Y, Harii N, Napolitano G, Tatone D, Bucci I, Piantelli M, Monaco F, Kohn LD. The flavonoid quercetin regulates growth and gene expression in rat FRTL-5 thyroid cells. Guardia T, Rotelli AE, Juarez AO, Pelzer LE.

Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin, and hesperidin on adjuvant arthritis in rat. Hanninen, Kaartinen K, Rauma AL, Nenonen M, Torronen R, Hakkinen AS, Adlercreutz H, Laakso J.

Antioxidants in vegan diet and rheumatic disorders. Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC. Food Chem Toxicol. Kleemann R, Verschuren L, Morrison M, et al. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models.

Knekt P, Isotupa S, Rissanen H, Heliovaara M, Jarvinen R, Hakkinen S et al. Quercetin intake and the incidence of cerebrovascular disease. Eur J Clin Nut. Kurowska EM, Spence JD, Jordan J, Wetmore S, Freeman DJ, Piche LA, Serratore P.

HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Lam TK, Rotunno M, Lubin JH, et al. Dietary quercetin, quercetin-gene interaction, metabolic gene expression in lung tissue and lung cancer risk.

Lamson DW, Brignall MS. Antioxidants and cancer III: quercetin. Alt Med Rev. Li N, Sun C, Zhou B, et al. Low concentration of quercetin antagonizeds the cytotoxic effects of anti-neoplastic drugs in ovarian cancer.

PLoS One. Longanga OA, Vercruysse A, Foriers A. Contribution to the ethnobotanical, phytochemical and pharmacological studies of traditionally used medicinal plants in the treatment of dysentery and diarrhoea in Lomela area, Democratic Republic of Congo DRC.

Mackraj I, Govender T, Ramesar S. The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. In this study including patients with prehypertension, a month Tai Chi intervention was more effective than aerobic exercise in reducing SBP.

These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations w. The effect of an encapsulated formulation Vascanox® HP that combines dietary sources of inorganic NO3- and S-allylcysteine SAC , a source of H2S from garlic, on NO bioavailability is presented.

Approximately one in five patients who underwent CABG also had high Lp a. High Lp a at baseline was associated with increased all-cause mortality and risk for adverse events after surgery. Extent and progression of coronary artery calcification CAC are strong predictors of myocardial infarction and mortality.

Our study provides evidence for a causality between dark chocolate intake and a reduced risk of essential hypertension EH , which has important implications for the prevention of EH in the population.

Quercetin, the most Protein intake for weight loss dietary flavonol or pigment, has antioxidant effects that may benefit cardiovascular disease, cancer, Quercetin and blood pressure blodo disorders. Bloox like quercetin are present Garlic in herbal remedies, vegetables, fruits, grains, teas predsure wine. The beneficial effects of flavonoids like quercetin come from their ability to function as antioxideants inside your body. The evidence regarding its effects on blood pressure BP has not been conclusive. A recent study assessed the impact of quercetin on blood pressure through a systematic review and meta-analysis of available randomized controlled trials. Methods and results: The authors identifed studies examining the impact of quercetin on BP as was was reported in 7 research reports patients. Quercetin and blood pressure

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