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Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

Migliori M, Cantaluppi V, Mannari C, Bertelli AA, Medica D, Quercia AD, Navarro V, Scatena A, Giovannini L, Biancone L, Panichi V - PLoS ONE (2015)

Bottom Line: The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production.In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.

ABSTRACT

Introduction: Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities.

Aim of the study: The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.

Results: CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.

Conclusion: The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

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Related in: MedlinePlus

Ach induced NO production by HUVECs.Ach stimulation increased NO release, revealed by chemiluminescence. TYR 1μM and 100nM did not affect Ach-induced NO release (Fig. 1A); CAF enhanced Ach-induced NO release in a dose-dependent manner (Fig. 1B) (p<0.05 CAF vs. controls or vs. Ach at all time points considered). Results are expressed as average±1SD of 6 different experiments.
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pone.0117530.g001: Ach induced NO production by HUVECs.Ach stimulation increased NO release, revealed by chemiluminescence. TYR 1μM and 100nM did not affect Ach-induced NO release (Fig. 1A); CAF enhanced Ach-induced NO release in a dose-dependent manner (Fig. 1B) (p<0.05 CAF vs. controls or vs. Ach at all time points considered). Results are expressed as average±1SD of 6 different experiments.

Mentions: Ach stimulation increased NO production by HUVECs in respect to baseline. Chemiluminescence decreased at every time point recorded even though at the end of observation (180 sec) remained higher than in unstimulated cells (Fig. 1A-B). However, TYR and CAF induced different responses in HUVECs: 100nM and 1μM TYR did not affect Ach-induced NO release (Fig. 1A). By contrast, CAF enhanced Ach-induced NO release in a dose-dependent manner (Fig. 1B). CAF-induced NO production remained at plateau for 25 sec., with a subsequent decrease. We then evaluated in HUVECs the effect of different phenols on NO production independent by Ach stimulation (Fig. 2). L-Arg and L-NAME were used as positive and negative controls, respectively. NO-generated chemiluminescence confirmed the lack of effect of TYR, whereas CAF increased NO production in a dose-dependent manner (Fig. 2).


Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

Migliori M, Cantaluppi V, Mannari C, Bertelli AA, Medica D, Quercia AD, Navarro V, Scatena A, Giovannini L, Biancone L, Panichi V - PLoS ONE (2015)

Ach induced NO production by HUVECs.Ach stimulation increased NO release, revealed by chemiluminescence. TYR 1μM and 100nM did not affect Ach-induced NO release (Fig. 1A); CAF enhanced Ach-induced NO release in a dose-dependent manner (Fig. 1B) (p<0.05 CAF vs. controls or vs. Ach at all time points considered). Results are expressed as average±1SD of 6 different experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390339&req=5

pone.0117530.g001: Ach induced NO production by HUVECs.Ach stimulation increased NO release, revealed by chemiluminescence. TYR 1μM and 100nM did not affect Ach-induced NO release (Fig. 1A); CAF enhanced Ach-induced NO release in a dose-dependent manner (Fig. 1B) (p<0.05 CAF vs. controls or vs. Ach at all time points considered). Results are expressed as average±1SD of 6 different experiments.
Mentions: Ach stimulation increased NO production by HUVECs in respect to baseline. Chemiluminescence decreased at every time point recorded even though at the end of observation (180 sec) remained higher than in unstimulated cells (Fig. 1A-B). However, TYR and CAF induced different responses in HUVECs: 100nM and 1μM TYR did not affect Ach-induced NO release (Fig. 1A). By contrast, CAF enhanced Ach-induced NO release in a dose-dependent manner (Fig. 1B). CAF-induced NO production remained at plateau for 25 sec., with a subsequent decrease. We then evaluated in HUVECs the effect of different phenols on NO production independent by Ach stimulation (Fig. 2). L-Arg and L-NAME were used as positive and negative controls, respectively. NO-generated chemiluminescence confirmed the lack of effect of TYR, whereas CAF increased NO production in a dose-dependent manner (Fig. 2).

Bottom Line: The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production.In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.

ABSTRACT

Introduction: Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities.

Aim of the study: The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.

Results: CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.

Conclusion: The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

Show MeSH
Related in: MedlinePlus