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- Olive (Olea europaea, Oleaceae) Leaf
- Oxidative Stress
- Cardiovascular Disease
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Date:
01-15-2016 | HC# 071523-536
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Re: Olive Leaf Constituents Reduce Myocardial Oxidative Damage
Efentakis P, Iliodromitis EK, Mikros E, et al.
Effects of the olive tree leaf
constituents on myocardial oxidative damage and atherosclerosis. Planta Med. June 2015;81(8):648-654.
Olive (Olea europaea, Oleaceae) leaf extract has
antioxidant, anti-inflammatory, antihypertensive, vasodilator, antithrombotic,
and hypoglycemic properties. The most abundant constituents of the dried leaf
extract are oleuropein, oleuropein aglycone, oleacein, hydroxytyrosol, tyrosol,
and elenolic acid. Research suggests that olive leaf extracts can mitigate the
oxidative stress and inflammation associated with the development of
cardiovascular disease (CVD). This article reviews the effects of olive leaf
extract and its major constituents on myocardial oxidative damage and
atherosclerosis.
The production of reactive oxygen species (ROS)
results in oxidative stress. Key factors in the progression of CVD associated
with oxidative stress are endothelial damage, reduced production of endothelial
nitric oxide synthase (eNOS) and thus, decreased nitric oxide (NO) concentrations,
depressed levels of endogenous enzymes that neutralize ROS, and increased
levels of oxidized low-density lipoproteins (ox-LDLs).
Oleuropein is a potent
antioxidant with the ability to scavenge superoxides and hydroxyl radicals. In
vitro and in vivo studies have found that oleuropein decreases LDL oxidation
and lowers concentrations of ROS and biomarkers of oxidative stress, as well as
total cholesterol and triglycerides. Among the olive leaf constituents,
oleuropein has the greatest anti-atherosclerotic activity. In animal models,
oleuropein protected against the effects of ischemia and reduced infarct size. In
addition, oleuropein supplementation increased superoxide dismutase
concentrations and reduced the risk of thrombosis.
Oleuropein aglycone,
a metabolite of oleuropein also referred to as 3,4-DHPEA-EA, has antioxidant activity comparable to caffeic acid, oleuropein, and hydroxytyrosol, and has also been found
to reduce the oxidation of LDL.
The oleuropein
metabolite oleacein has even more potent antioxidant and anti-inflammatory
properties than oleuropein. It inhibits the production of ROS and decreases the
pro-inflammatory response. Oleacein can permeate the cell membrane of red blood
cells and protect against oxidative damage. It directly inhibits 5-lipoxygenase
and protects against endothelial damage in a dose-dependent manner. The
anti-ischemic properties of oleacein have not been investigated.
In vitro studies show that hydroxytyrosol prevents
ROS damage, upregulates the expression of endogenous antioxidants, and reduces LDL
oxidation. However, there is conflicting experimental evidence regarding the
anti-atherosclerotic properties of hydroxytyrosol, and studies evaluating its
cytoprotective effects against ischemia-reperfusion injury are lacking.
Experimental studies have shown that tyrosol
reduces lipid peroxidation and oxidative stress but at a significantly lower
extent than hydroxytyrosol. Tyrosol upregulates eNOS expression, reduces
infarct size, and ameliorates ischemia-reperfusion injury.
There is no evidence that elenolic acid has
cardioprotective effects; however, very few studies have been conducted. Elenolic
acid is used as a marker of olive maturity.
Amongst the olive
leaf constituents, oleuropein and hydroxytyrosol are
the most effective anti-atherosclerotic agents. Compared to oleuropein,
hydroxytyrosol is a better free radical scavenger and provides superior protection
against LDL oxidation. However, the ethanolic extract of olive leaves showed
better protection against oxidative stress and toxicity than the individual phenolic
compounds. In the protection against oxidative hemolysis, the order of activity
was oleacein > oleuropein aglycone > hydroxytyrosol = oleuropein. Only
hydroxytyrosol protected against NO-mediated oxidative stress and it had the
highest antioxidant activity compared to oleuropein and tyrosol. Olive phenols
have been shown to significantly reduce lipoprotein oxidation and aging-induced
oxidative stress, and protect against DNA and endothelial damage.
In vitro, olive leaf extract protected against LDL oxidation. In animal
models, olive leaf extract attenuated the symptoms of metabolic syndrome,
improved lipid profiles, and reduced levels of oxidative stress markers and
inflammatory cytokines. A clinical study evaluating the effects of an olive
leaf extract containing 5.4 mg/ml oleuropein found that it decreased
inflammatory markers, H2O2, and platelet activation.
In summary, olive
leaf extracts and their phenolic constituents have been shown to reduce
oxidative stress in animal models. Protection against LDL oxidation with
concomitant improvements in endogenous antioxidant levels and lipid profiles
has also been observed in vivo. These effects have primarily been attributed to
hydroxytyrosol and oleuropein. The anti-atherosclerotic,
hypocholesterolemic, and anti-ischemic activities of olive leaf extract and its
constituents need to be studied in further detail to elucidate the underlying
mechanisms of action. The authors conclude that olive leaf constituents have
beneficial effects on myocardial oxidative stress; however, the human trials
should be systematically reviewed to determine whether these effects are
clinically relevant.
—Cheryl
McCutchan, PhD
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