Micaela Gliozzi

IJC Metabolic & Endocrine

Gliozzi, Micaela

Elsevier - Publisher Connector 

manipulations of the utilization of metabolic substrates should result
in an improvement of myocardial ischemia and of left ventricular
function.
Therefore, the metabolic changes of diabetes alter myocardial
metabolism reducing cardiac susceptibility to ischemic stimuli and
cardiac performance. In diabetic coronary patients the episodes of
transient myocardial ischemia coupled with the chronic myocardial
hypoperfusion cause a progressive decline of left ventricular
function. The inhibition of FFA oxidation improves cardiac metabo-
lism at rest, increases the cardiac ischemic and therefore reduces the
decline of left ventricular function due to chronic hypoperfusion and
repetitive episodes of myocardial ischemia.
doi:10.1016/j.ijcme.2015.05.003
Natural antioxidants: A novel approach for counteracting
cardiometabolic risk
Micaela Gliozzi
IRC-FSH Department of Health Sciences, University “Magna Græcia” of
Catanzaro, Italy
Bergamot (Citrus Bergamia) is an endemic plant of Calabrian region
in Southern Italy. To date, 95% ofworldwide bergamot production occurs
in the Ionic area of Calabria, where soil characteristics and pH (b6.5–7.5)
are particularly suitable for its cultivation.
Bergamot essential oil (BEO) is made up of a volatile fraction and a
non-volatile residue. Volatile components make up approximately 93–
96% byweight of bergamot oil, while the non-volatile residue represents
the remaining 4–7%. The non-volatile fraction is a mixture of monoter-
pene and sesquiterpene hydrocarbons (such as limonene, γ-terpinene,
and β-pinene) and their oxygenated derivatives (linalool and linalyl
acetate). The non-volatile (4–7% of total) fraction containing coumarins
and psoralens [such as bergapten (5-methoxypsoralen) and berga-
mottine (5-geranyloxypsoralen)]. The non-volatile residue, which
inﬂuences the olfactory properties of the oil, contains waxes and
polymethoxylated ﬂavones other than about 0.2% bergapten which is
responsible for the phototoxicity of BEO. The bergapten-free extract of
the essence (BEO-BF) together with a natural essence deprived of the
hydrocarbon fraction and of bergapten (BEO-HF/BF) are prepared by
extractive industries for perfumery and cosmetic uses [2,3].
Bergamot differs from other citrus fruits not only because of the
composition of these ﬂavonoids, but also because of their particularly
high content. Some of the ﬂavonoids such as naringin, present also in
grapefruit, have already been shown to be active in animal models of
atherosclerosis, while neoeriocitrin and rutin exhibited the strongest
capacity to inhibit LDL oxidation. Importantly, bergamot juice is rich in 3-
hydroxy-3-methylglutaryl neohesperidosides of hesperetin (bru-
tieridine) and naringenin (melitidine) with ability to inhibit HMG-CoA
reductase. These compounds most likely contribute to the important
hypolipemic effects of bergamot juice and vasoprotective effects of
bergamot oil derivatives in rats and in humans as demonstrated by
recent clinical studies carried out in patients treated with bergamot-
derived polyphenolic fraction (BPF) obtained concentrating bergamot
juice in a form of powder, enriched in ﬂavonoids.
Epidemiologic studies have demonstrated that a Mediterranean diet
rich in olive oil is associated with decrease in risk for cardiovascular
disease, obesity, and diabetes. Although some of the protection may be
from the unsaturated fatty acid components of such a diet, additional
smallmolecules found in olive oil and olive plantsmay confer protection,
including the polyphenol oleuropein and hydroxytyrosol.
The two main sources of olive polyphenols are olive leaves and
the waste from the olive oil industry. Olive leaves have the highest
antioxidant and scavenging power among the different parts of the
olive tree. There are ﬁve groups of phenolic compounds principally
present in olive leaves: oleuropeosides (oleuropein and ver-
bascoside); ﬂavones (luteolin-7-glucoside, apigenin-7-glucoside,
diosmetin-7- glucoside, luteolin, and diosmetin); ﬂavonols (rutin);
ﬂavan-3-ols (catechin), and substituted phenols (tyrosol, hydroxy-
tyrosol, vanillin, vanillic acid, and caffeic acid). The most abundant
compound in olive leaves is oleuropein, followed by hydroxytyrosol,
a precursor of oleuropein, the ﬂavone-7-glucosides of luteolin and
apigenin, and verbascoside, a conjugated glucoside of hydroxytyrosol
and caffeic acid.
Oleuropein prevents cardiac disease by protecting membrane
from lipid oxidation, by affecting coronary blood vessel dilation, by
exerting antiarhythmic action, by improving lipid metabolism, by
protecting enzymes, by preventing hypertensive cell death in cancer
patients and by its antiviral properties.
In the current review, we want to highlight the potential
beneﬁcial effects of synergistic action of BPF and oleuropein.
There is evidence to suggest that the anti-hypertensive activity of
the olive leaf extract lies probably in its content of oleuropein acting
synergistically with other active substances to exert both ACE
inhibitory and calcium channel blocking activities.
The anti-hypertensive and cholesterol-lowering actions hypoth-
esized for oleuropein suggest its potential synergistically action with
BPF, able to induce in patients both hypolipemic and hypoglycaemic
effects other than an improvement of reactive vasodilatation. This
latter action also underlines an improvement of endothelial function
in patients at risk of atherosclerosis.
Since oxidative stress has been shown to reduce reactive NO-
dependent vasodilatation, it is likely that BPF may well attenuate
overproduction of oxygen reactive species in the vascular wall
thereby restoring the imbalanced endothelial function in hyperlipe-
mic patients.
doi:10.1016/j.ijcme.2015.05.004
A modern approach in cardiometabolic risk — The role of
oxidative stress and LOX-1 expression in endothelial
dysfunction and cardiometabolic risk
Vincenzo Mollace, MD
IRC-FSH Department of Health Sciences, University “Magna Græcia” of
Catanzaro, Italy
IRCCS San Raffaele, Rome, Italy
Background: Overproduction of oxidized-low density lipoproteins
(oxyLDL) has been found to contribute in endothelial cell (EC)
dysfunction thereby leading to atherosclerosis development and
progression. In particular, oxyLDL lead to apoptotic cell death of EC via
oxidative stress production, mostly subsequent to overexpression of the
scavenger receptor LOX-1. Here, we hypothesize that LOX-1 expression
in EC represents a crucial event which attenuates protective autophagic
response, thereby enhancing programmed endothelial cell death.
Methods and results: Bovine aortic endothelial cells (BAEC) in culture
were exposed to oxyLDL (1–100 μM). After 48 h incubation, oxyLDL
produced apoptotic cell death of BAEC as detected by FACS analysis, an
effect counteracted by antioxidant N-acetyl-cysteine (NAC) as well as by
the NO-donor SNAP. OxyLDL-induced apoptotic cell death was also
accompanied by reduced VEGF-dependent phosphorylation of constitu-
tive NO synthase (cNOS) in BAEC and consistent attenuation of
autophagic response as detected by expression of beclin-1 and LC3,
two reliable biomarkers of autophagy. Moreover, silencing LOX-1
receptor signiﬁcantly restored LC3 expression in oxyLDL-treated BAEC,
thus suggesting a key role of LOX-1 overproduction in oxyLDL-induced
endothelial dysfunction.
Abstracts2
Open access under CC BY-NC-ND license.


Natural antioxidants: A novel approach for counteracting cardiometabolic risk 

Open Access Repository

manipulations of the utilization of metabolic substrates should resultin an improvement of myocardial ischemia and of left ventricularfunction.Therefore, the metabolic changes of diabetes alter myocardialmetabolism reducing cardiac susceptibility to ischemic stimuli andcardiac performance. In diabetic coronary patients the episodes oftransient myocardial ischemia coupled with the chronic myocardialhypoperfusion cause a progressive decline of left ventricularfunction. The inhibition of FFA oxidation improves cardiac metabo-lism at rest, increases the cardiac ischemic and therefore reduces thedecline of left ventricular function due to chronic hypoperfusion andrepetitive episodes of myocardial ischemia.doi:10.1016/j.ijcme.2015.05.003Natural antioxidants: A novel approach for counteractingcardiometabolic riskMicaela GliozziIRC-FSH Department of Health Sciences, University “Magna Græcia” ofCatanzaro, ItalyBergamot (Citrus Bergamia) is an endemic plant of Calabrian regionin Southern Italy. To date, 95% ofworldwide bergamot production occursin the Ionic area of Calabria, where soil characteristics and pH (b6.5–7.5)are particularly suitable for its cultivation.Bergamot essential oil (BEO) is made up of a volatile fraction and anon-volatile residue. Volatile components make up approximately 93–96% byweight of bergamot oil, while the non-volatile residue representsthe remaining 4–7%. The non-volatile fraction is a mixture of monoter-pene and sesquiterpene hydrocarbons (such as limonene, γ-terpinene,and β-pinene) and their oxygenated derivatives (linalool and linalylacetate). The non-volatile (4–7% of total) fraction containing coumarinsand psoralens [such as bergapten (5-methoxypsoralen) and berga-mottine (5-geranyloxypsoralen)]. The non-volatile residue, whichinfluences the olfactory properties of the oil, contains waxes andpolymethoxylated flavones other than about 0.2% bergapten which isresponsible for the phototoxicity of BEO. The bergapten-free extract ofthe essence (BEO-BF) together with a natural essence deprived of thehydrocarbon fraction and of bergapten (BEO-HF/BF) are prepared byextractive industries for perfumery and cosmetic uses [2,3].Bergamot differs from other citrus fruits not only because of thecomposition of these flavonoids, but also because of their particularlyhigh content. Some of the flavonoids such as naringin, present also ingrapefruit, have already been shown to be active in animal models ofatherosclerosis, while neoeriocitrin and rutin exhibited the strongestcapacity to inhibit LDL oxidation. Importantly, bergamot juice is rich in 3-hydroxy-3-methylglutaryl neohesperidosides of hesperetin (bru-tieridine) and naringenin (melitidine) with ability to inhibit HMG-CoAreductase. These compounds most likely contribute to the importanthypolipemic effects of bergamot juice and vasoprotective effects ofbergamot oil derivatives in rats and in humans as demonstrated byrecent clinical studies carried out in patients treated with bergamot-derived polyphenolic fraction (BPF) obtained concentrating bergamotjuice in a form of powder, enriched in flavonoids.Epidemiologic studies have demonstrated that a Mediterranean dietrich in olive oil is associated with decrease in risk for cardiovasculardisease, obesity, and diabetes. Although some of the protection may befrom the unsaturated fatty acid components of such a diet, additionalsmallmolecules found in olive oil and olive plantsmay confer protection,including the polyphenol oleuropein and hydroxytyrosol.The two main sources of olive polyphenols are olive leaves andthe waste from the olive oil industry. Olive leaves have the highestantioxidant and scavenging power among the different parts of theolive tree. There are five groups of phenolic compounds principallypresent in olive leaves: oleuropeosides (oleuropein and ver-bascoside); flavones (luteolin-7-glucoside, apigenin-7-glucoside,diosmetin-7- glucoside, luteolin, and diosmetin); flavonols (rutin);flavan-3-ols (catechin), and substituted phenols (tyrosol, hydroxy-tyrosol, vanillin, vanillic acid, and caffeic acid). The most abundantcompound in olive leaves is oleuropein, followed by hydroxytyrosol,a precursor of oleuropein, the flavone-7-glucosides of luteolin andapigenin, and verbascoside, a conjugated glucoside of hydroxytyrosoland caffeic acid.Oleuropein prevents cardiac disease by protecting membranefrom lipid oxidation, by affecting coronary blood vessel dilation, byexerting antiarhythmic action, by improving lipid metabolism, byprotecting enzymes, by preventing hypertensive cell death in cancerpatients and by its antiviral properties.In the current review, we want to highlight the potentialbeneficial effects of synergistic action of BPF and oleuropein.There is evidence to suggest that the anti-hypertensive activity ofthe olive leaf extract lies probably in its content of oleuropein actingsynergistically with other active substances to exert both ACEinhibitory and calcium channel blocking activities.The anti-hypertensive and cholesterol-lowering actions hypoth-esized for oleuropein suggest its potential synergistically action withBPF, able to induce in patients both hypolipemic and hypoglycaemiceffects other than an improvement of reactive vasodilatation. Thislatter action also underlines an improvement of endothelial functionin patients at risk of atherosclerosis.Since oxidative stress has been shown to reduce reactive NO-dependent vasodilatation, it is likely that BPF may well attenuateoverproduction of oxygen reactive species in the vascular wallthereby restoring the imbalanced endothelial function in hyperlipe-mic patients.doi:10.1016/j.ijcme.2015.05.004A modern approach in cardiometabolic risk — The role ofoxidative stress and LOX-1 expression in endothelialdysfunction and cardiometabolic riskVincenzo Mollace, MDIRC-FSH Department of Health Sciences, University “Magna Græcia” ofCatanzaro, ItalyIRCCS San Raffaele, Rome, ItalyBackground: Overproduction of oxidized-low density lipoproteins(oxyLDL) has been found to contribute in endothelial cell (EC)dysfunction thereby leading to atherosclerosis development andprogression. In particular, oxyLDL lead to apoptotic cell death of EC viaoxidative stress production, mostly subsequent to overexpression of thescavenger receptor LOX-1. Here, we hypothesize that LOX-1 expressionin EC represents a crucial event which attenuates protective autophagicresponse, thereby enhancing programmed endothelial cell death.Methods and results: Bovine aortic endothelial cells (BAEC) in culturewere exposed to oxyLDL (1–100 μM). After 48 h incubation, oxyLDLproduced apoptotic cell death of BAEC as detected by FACS analysis, aneffect counteracted by antioxidant N-acetyl-cysteine (NAC) as well as bythe NO-donor SNAP. OxyLDL-induced apoptotic cell death was alsoaccompanied by reduced VEGF-dependent phosphorylation of constitu-tive NO synthase (cNOS) in BAEC and consistent attenuation ofautophagic response as detected by expression of beclin-1 and LC3,two reliable biomarkers of autophagy. Moreover, silencing LOX-1receptor significantly restored LC3 expression in oxyLDL-treated BAEC,thus suggesting a key role of LOX-1 overproduction in oxyLDL-inducedendothelial dysfunction.Abstracts2Open access under CC BY-NC-ND license.

Natural antioxidants: A novel approach for counteracting cardiometabolic risk

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