Epicatechin’s cardiovascular protective effects are mediated via opioid receptors and nitric oxide

MacRae, Kirsty; Connolly, Kylie; Vella, Rebecca; Fenning, Andrew

doi:10.1007/s00394-018-1650-0

Cited by 16 publications

(21 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that damaged endothelial cells show greater levels of oxidative stress and decreased NO bioavailability, the observation that DOCA + E aortas did not demonstrate a similar trend towards greater ACh sensitivity also indicates the importance of eNOS- and NO-enhancing properties in the vascular effects of epicatechin treatment. Our results are further supported by data from MacRae et al [ 12 ] showing that epicatechin’s vasodilatory effects require a functional endothelial layer, and when the endothelium is damaged or absent, no epicatechin-mediated vasodilation occurs. This helps to explain the difference in epicatechin-mediated effects within the vasculature of both the UNX + E and DOCA + E rats.…”

Section: Discussionsupporting

confidence: 90%

“…Research has shown that epicatechin possesses many cardioprotective and antioxidative properties, including the ability to increase endothelial nitric oxide synthase activation, increasing nitric oxide levels [ 6 , 10 ], and inhibit nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [ 11 ], which is a source of cellular reactive oxygen species. It has been suggested that the vascular effects of epicatechin are mediated through opioid receptor activation and importantly that a functional endothelium is required in order for epicatechin to achieve any vascular effects [ 12 ]. Additionally, epicatechin has also been reported to attenuate tumour necrosis factor-alpha (TNF-

)-mediated inflammation and insulin resistance [ 1 ] and mitochondrial damage [ 4 ], all of which have been shown to be associated with myocardial injury.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

(−)-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

et al. 2018

Self Cite

View full text Add to dashboard Cite

(−)-Epicatechin (E) is a flavanol found in green tea and cocoa and has been shown to attenuate tumour necrosis factor alpha (TNF-α)-mediated inflammation, improve nitric oxide levels, promote endothelial nitric oxide synthase (eNOS) activation and inhibit NADPH oxidase. This study investigated the effect of 28 days of low epicatechin dosing (1 mg/kg/day) on the cardiovascular function of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Wistar rats (n = 120, 8 weeks of age) underwent uninephrectomy and were randomised into four groups (uninephrectomy (UNX), UNX + E, DOCA, DOCA + E). DOCA and DOCA + E rats received 1% NaCl drinking water along with subcutaneous injections of 25 mg deoxycorticosterone-acetate (in 0.4 mL of dimethylformamide) every fourth day. UNX + E and DOCA + E rats received 1 mg/kg/day of epicatechin by oral gavage. Single-cell micro-electrode electrophysiology, Langendorff isolated-heart assessment and isolated aorta and mesenteric organ baths were used to assess cardiovascular parameters. Serum malondialdehyde concentration was used as a marker of oxidative stress. Myocardial stiffness was increased and left ventricular compliance significantly diminished in the DOCA control group, and these changes were attenuated by epicatechin treatment (p < 0.05). Additionally, the DOCA + E rats showed significantly reduced blood pressure and malondialdehyde concentrations; however, there was no improvement in left ventricular hypertrophy, electrophysiology or vascular function. This study demonstrates the ability of epicatechin to reduce blood pressure, prevent myocardial stiffening and preserve cardiac compliance in hypertrophied DOCA-salt rat hearts.

show abstract

Section: Discussionsupporting

confidence: 90%

)-mediated inflammation and insulin resistance [ 1 ] and mitochondrial damage [ 4 ], all of which have been shown to be associated with myocardial injury.…”

Section: Introductionmentioning

confidence: 99%

(−)-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast to our findings, in a model of hypertensive rats treated with Epi, the final vasodilatory response to ACh was not significantly different vs. controls ( Kluknavsky et al, 2016 ). As MacRae et al, proposed the explanation for these discrepancies may be related to the fact that the vasodilatory effects of Epi require a functional endothelial layer and when the endothelium is severely damaged or absent, Epi-mediated vasodilation is poor ( MacRae et al, 2019 ). Being aging a less aggressive and slower “damaging” process than hypertension it also helps to explain the difference in Epi-mediated effects.…”

Section: Discussionmentioning

confidence: 99%

Arginase inhibition by (−)-Epicatechin reverses endothelial cell aging

Garate‐Carrillo

Navarrete‐Yanez

Ortiz-Vilchis

et al. 2020

European Journal of Pharmacology

View full text Add to dashboard Cite

Endothelial dysfunction (EnD) occurs with aging and endothelial nitric oxide (NO) production by NO synthase (NOS) can be impaired. Low NO levels have been linked to increased arginase (Ar) activity as Ar competes with NOS for L-arginine. The inhibition of Ar activity can reverse EnD and (−)-epicatechin (Epi) inhibits myocardial Ar activity. In this study, through in silico modeling we demonstrate that Epi interacts with Ar similarly to its inhibitor Norvaline (Norv). Using in vitro and in vivo models of aging, we examined Epi and Norv-inhibition of Ar activity and its endothelium-protective effects. Bovine coronary artery endothelial cells (BCAEC) were treated with Norv (10 μM), Epi (1 μM) or the combination (Epi + Norv) for 48 h. Ar activity increased in aged BCAEC, with decreased NO generation. Treatment decreased Ar activity to levels seen in young cells. Epi and Epi + Norv decreased nitrosylated Ar levels by ~25% in aged cells with lower oxidative stress (~25%) (dihydroethidium) levels. In aged cells, Epi and Epi + Norv restored the eNOS monomer/dimer ratio, protein expression levels and NO production to those of young cells. Furthermore, using 18 month old rats 15 days of treatment with either Epi (1 mg/kg), Norv (10 mg/kg) or combo, decreased hypertension and improved aorta vasorelaxation to acetylcholine, blood NO levels and tetra/dihydribiopterin ratios in cultured rat aortic endothelial cells. In conclusion, results provide evidence that inhibiting Ar with Epi reverses aged-related loss of eNOS function and improves vascular function through the modulation of Ar and eNOS protein levels and activity.

show abstract

“…Flavan-3-ols and PAs are potent antioxidants with multiple benefits to human health (Xie and Dixon, 2005 ). Multiple compounds from these two groups, such as CA, EPC, EGC, EGCG, procyanidin B2, and procyanidin A2 ( Figure 2 ), have been shown to have antiviral function (de Bruyne et al, 1999 ; Iwasawa et al, 2009 ), antibacterial activity (Molan et al, 2001 ; Howell et al, 2005 ), anticancer (Ohata et al, 2005 ; Suganuma et al, 2011 ), anti-cardiovascular diseases (Loke et al, 2008 ; Panneerselvam et al, 2010 ; MacRae et al, 2019 ), and anti-aging diseases (Levites et al, 2003 ; Li et al, 2004 ; Weinreb et al, 2004 ). In particular, the anti-viral activity suggests that flavan-3-ols and PAs are appropriate targets for screening potential anti-SARS-Cov-2 medicines.…”

Section: Introductionmentioning

confidence: 99%

Docking Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2

Zhu

Xie

2020

Front. Plant Sci.

View full text Add to dashboard Cite

We report to use the main protease (Mpro) of SARS-Cov-2 to screen plant flavan-3-ols and proanthocyanidins. Twelve compounds, (–)-afzelechin (AF), (–)-epiafzelechin (EAF), (+)-catechin (CA), (–)-epicatechin (EC), (+)-gallocatechin (GC), (–)-epigallocatechin (EGC), (+)-catechin-3-O-gallate (CAG), (–)-epicatechin-3-O-gallate (ECG), (–)-gallocatechin-3-O-gallate (GCG), (–)-epigallocatechin-3-O-gallate (EGCG), procyanidin A2 (PA2), and procyanidin B2 (PB2), were selected for docking simulation. The resulting data predicted that all 12 metabolites could bind to Mpro. The affinity scores of PA2 and PB2 were predicted to be −9.2, followed by ECG, GCG, EGCG, and CAG, −8.3 to −8.7, and then six flavan-3-ol aglycones, −7.0 to −7.7. Docking characterization predicted that these compounds bound to three or four subsites (S1, S1′, S2, and S4) in the binding pocket of Mpro via different spatial ways and various formation of one to four hydrogen bonds. In vitro analysis with 10 available compounds showed that CAG, ECG, GCG, EGCG, and PB2 inhibited the Mpro activity with an IC50 value, 2.98 ± 0.21, 5.21 ± 0.5, 6.38 ± 0.5, 7.51 ± 0.21, and 75.3 ± 1.29 μM, respectively, while CA, EC, EGC, GC, and PA2 did not have inhibitory activities. To further substantiate the inhibitory activities, extracts prepared from green tea (GT), two muscadine grapes (MG), cacao, and dark chocolate (DC), which are rich in CAG, ECG, GAG, EGCG, or/and PB2, were used for inhibitory assay. The resulting data showed that GT, two MG, cacao, and DC extracts inhibited the Mpro activity with an IC50 value, 2.84 ± 0.25, 29.54 ± 0.41, 29.93 ± 0.83, 153.3 ± 47.3, and 256.39 ± 66.3 μg/ml, respectively. These findings indicate that on the one hand, the structural features of flavan-3-ols are closely associated with the affinity scores; on the other hand, the galloylation and oligomeric types of flavan-3-ols are critical in creating the inhibitory activity against the Mpro activity.

show abstract

Epicatechin’s cardiovascular protective effects are mediated via opioid receptors and nitric oxide

Abstract: These findings suggest epicatechin's vascular responses and cardioprotective effects are mediated through opioid receptors, nitric oxide, potassium channel and calcium channel activation and highlight the importance of the endothelium/nitric oxide in epicatechin mediated vasorelaxation.

Cited by 16 publications

References 61 publications

(−)-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

(−)-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

Arginase inhibition by (−)-Epicatechin reverses endothelial cell aging

Docking Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2

Contact Info

Product

Resources

About