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An Overview of the Modulatory Effects of Oleic Acid in Health and Disease

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Evidences in the last years have showed the effects of oleic acid (OA) in human health and disease. Olive oil, rich in oleic acid, is supposed to present modulatory effects in a wide physiological functions, while some studies also suggest a beneficial effect on cancer, autoimmune and inflammatory diseases, besides its ability to facilitate wound healing. Although the OA role in immune responses are still controversial, the administration of olive oil containing diets may improve the immune response associated to a more successful elimination of pathogens such as bacteria and fungi, by interfering in many components of this system such as macrophages, lymphocytes and neutrophils. Then, novel putative therapies for inflammatory and infectious diseases could be developed based on the characteristics presented by unsaturated fatty acids like OA. Finally, the purpose of this work was to review some of the modulatory effects of OA on inflammatory diseases and health, aiming at high lightening its potential role on the future establishment of novel therapeutic approaches for infections, inflammatory, immune, cardiovascular diseases or skin repair based on this fatty acid mainly found in the Mediterranean diet.
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Mini-Reviews in Medicinal Chemistry, 2013, 13, 000-000 1
1389-5575/13 $58.00+.00 © 2013 Bentham Science Publishers
An Overview of the Modulatory Effects of Oleic Acid in Health and
Disease
Helioswilton Sales-Campos1, Patrícia Reis de Souza1, Bethânea Crema Peghini3,
João Santana da Silva2 and Cristina Ribeiro Cardoso1,*
1Departamento de Análises Clínicas, Toxicológicas e Bromatológicas – Faculdade de Ciências Farmacêuticas de
Ribeirão Preto; 2Departamento de Bioquímica e Imunologia – Faculdade de Medicina de Ribeirão Preto, Universidade
de São Paulo, Ribeirão Preto, São Paulo, Brazil; 3Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais,
Brazil
Abstract: Evidences in the last years have showed the effects of oleic acid (OA) in human health and disease. Olive oil,
rich in oleic acid, is supposed to present modulatory effects in a wide physiological functions, while some studies also
suggest a beneficial effect on cancer, autoimmune and inflammatory diseases, besides its ability to facilitate wound
healing. Although the OA role in immune responses are still controversial, the administration of olive oil containing diets
may improve the immune response associated to a more successful elimination of pathogens such as bacteria and fungi,
by interfering in many components of this system such as macrophages, lymphocytes and neutrophils. Then, novel
putative therapies for inflammatory and infectious diseases could be developed based on the characteristics presented by
unsaturated fatty acids like OA. Finally, the purpose of this work was to review some of the modulatory effects of OA on
inflammatory diseases and health, aiming at high lightening its potential role on the future establishment of novel
therapeutic approaches for infections, inflammatory, immune, cardiovascular diseases or skin repair based on this fatty
acid mainly found in the Mediterranean diet.
Keywords: Oleic acid, modulatory effects, cancer, autoimmune and inflammatory diseases, wound healing.
INTRODUCTION
The concep t that specific fatty acids (FA) are necessary
for an appropriate growth of animals including humans was
first introduced by Burr and Burr in 1929, when Wistar rats
were depriv ed of dietary fat and there was an occurrence of a
“new deficiency disease” involving caudal necrosis [1].
However, until 1960s the importance of essential fatty acids
for human health was poorly considered. Their relevance
was primary highlighted in studies which described signs of
clinical deficiency in infants fed skimmed milk-based formula
[2] or in neonates receiving a fat-free parenteral nutrition [3,
4]. Therefore, b ased on a nutritional classification, fatty acids
that are not synthesized by humans and are indispensable for
development and health are known as essential while those
produced by humans are classified as non-essential fatty
acids. In this context linoleic and alpha-linolenic acids are
polyunsaturated fatty acids (PUFA) classified as essential
while monounsaturated fatty acids (MUFA) are classified as
non-essential [5].
The fatty acid classification in MUFA or PUFA is based
on the hydrocarbon bonds in their structural composition.
When a fatty acid has no double bonds in the hydrocarbon
*Address correspondence to this author at the School of Pharmaceutical
Sciences of Ribeirão Preto – USP, Department of Clinical, Toxicological
and Bromatologic Analysis, Av. do Café, s/n – 14040-903 Ribeirão
Preto/SP, Brazil; Tel: 16. 3602 0257; Fax: 16. 3633 6840;
E-mail: cristina@fcfrp.usp.br
chain it is named saturated fatty acid (SFA) and when it has
one or more double bonds it is classified as MUFA or PUFA,
respectively [6, 7]. Therefore, arachdonic acid [AA, C20:4
(-6)], linoleic acid [LA, C18:2 (-6)], docosahexanoic acid
[DHA, C22:6 (-3)], eicosapentanoic acid [EPA, C20:5 (-
3)] and linolenic acid [LA, C18:3 (-3)] are examples of
PUFA while oleic acid [OA, C18:1 (-9)] is a MUFA, a
non-essential fatty acid that has been recently described as a
regulator of immune function and health.
MUFA contribute to dietary fat consumption in many
parts of the world and in Mediterranean area it constitutes at
least one third of the total fatty acid intake [8]. Olive oil is
one of the most used culinary fat in Mediterranean diet [9]
being mainly composed by the MUFA oleic acid (OA),
which represents 70-80% of olive oil composition, besides
minor phenolic compounds [10]. In the last years many
studies described the contribution of olive oil to general
health, partly due to its high OA content [11-17], which was
demonstrated to lead to a reduction in cholesterol levels,
atherogenesis risk [5, 18-21], host versus graft response [22],
blood pressure and daily anti hypertensive drug intake [23].
In addition OA was demonstrated to induce beneficial anti-
inflammatory effects on auto immune diseases [24, 25],
protective effect on breast cancer and improvement of immune
system function [26-30]. Then, these well-documented
properties reinforce the importance to a better understanding
of the mechanisms of action and physiological changes
caused by oleic acid intake, esp ecially in human health.
2 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 Sales-Campos et al.
MODULATION OF LEUKOCYTES ACTIVITY AND
INFLAMMATORY PROCESS
A full and effective immune response to a host threatening
stimuli requires diverse and complementary mechanisms of
inflammation, cell activation, antibody production and
effector reactions, which include innate immune components
like granulocytes, natural killer cells, macrophages and their
soluble mediators, along with a more specialized adaptive
lymphocyte response. Therefore, some evidences suggested
that dietary lipids influence the activity and function of
numerous immune system components. These changes
comprise the modulation of innate and adaptive responses
including antigen presentation, lymphocyte proliferation,
cytokine production, granulocytes and natural killer cell
activity that may be modified by unsaturated fatty acids [31,
32]. So far, many mechanisms have been proposed to
explain the relationship between different fatty acids intake
and the immune system modulation both in humans and
experimental animals.
Regarding innate granulocytes function, an increase in
reactive oxygen species (ROS), that is essential for
neutrophil microbicidal activity, was observed in patients
who received olive oil emulsion when compared to those
who were given soybean oil emulsion [33, 34]. However, no
effect of olive oil emulsion was observed in other inflammatory
and immune parameters such as erythrocyte sedimentation
rate, production of C-reactive protein, TNF-, IL-6, IL-8 and
soluble receptors for IL-2 in humans [35]. Furthermore, the
olive oil intake did not change the mitogen stimulated human
lymphocytes proliferation while in rats there was an
inhibition of this parameter. Indeed, feeding laboratory
rodents a diet rich in olive oil resulted in the suppression of
natural killer cell activity (Fig. 1) [36], mitogen stimulated
proliferation [37, 38] and the expression of receptors for IL-2
and transferrin [37] in spleen lymphocytes. These differences
were probably due to the higher olive oil content provided to
the experimental animals that had reduced proliferation when
fed diets containing a range of 35.6-71.6% of olive oil
(approximately 60-130 g/Kg) in the total fatty acids while
humans received only 18.4% of olive oil content [39, 40].
Thus, in middle aged men who consumed either a control
diet or a diet containing foods enriched in highly refined
olive oil for 8 weeks there was no change in proliferation of
either whole blood cultures or peripheral blood mononuclear
cells in response to concanavalin A (Con A) [39].
However, contradictory findings are reported in the
literature regarding the effects of OA on immune function.
Cury-Boaventura et al. demonstrated that an olive oil-based
emulsion given to healthy volunteers led to decreased ex-
vivo lymphocyte proliferation (Fig. 1), besides having no
effect on neutrophils [33]. Additionally, studies conducted in
rats suggested that an olive oil emulsion, rich in OA, had no
effect in the inhibition of interleukin-2 (IL-2) receptor
expression [41], IL-2 production by lymphocytes, bacteremia
[42], chemotaxis, migration or pro-inflammatory cytokines
released by neutrophils [43], while these effects were
observed with soybean emulsion administration [33]. Then,
the modulatory role of OA on the immune response seems to
be dependent on the amount and the content of fatty acid
received by the subjects, animal species or the immune
parameter evaluated, although most studies provide strong
evidences for a relevant participation of this MUFA in the
immunity control. Moreover, further comparisons among the
effects of olive oil, safflower oil and a high OA sunflower oil
on the immune cell functions suggested that the effects
observed were due to OA rather than to the non lipid
component of olive oil [44].
Adhesion molecules are also imp licated in the immun e
responses, by interfering with the immunological synapse
formation and trans endothelial migration of leukocytes to
the antigen site in the inflammatory reactions. These
molecules also mediate leukocyte traffic to synovial fluid
and tissue in rheumatoid arthritis (RA), as well as the
formation of atherosclerotic plaques dependent on the
leukocyte endothelium interaction in cardiovascular diseases
[8]. A study using human saphenous vein endothelial cells
(HSVEC) preincubated with arachidonic acid (AA),
eicosapentanoic acid (EPA), docosahexaenoic acid (DHA) or
OA prior to stimulation with TNF- showed that OA and
DHA significantly decreased the expression of vascular cell
adhesion molecule-1 (VCAM-1) by HSVEC (Fig. 1) [45].
Other studies showed a decreased expression of the adhesion
molecules CD2, ICAM-1 and LFA-1 on spleen lymphocytes
of rats fed olive oil (Fig. 1) and fish oil containing -3
PUFA [22]. In addition, middle-aged men fed a diet with
18.4% content in MUFA showed a decreased expression of
the leukocyte adhesion molecule ICAM-1 in the peripheral
blood mononuclear cells, after 2 months of diet consumption,
when compared to values from a normal diet control group
[39]. Furthermore, healthy men and women living in a
religious community were subjected to different fat content
in diet during four consecutive dietary periods differing in
the fat content of saturated fatty acid, MUFA, linolenic (-3)
and linoleic (-6) PUFA. There was a lower monocyte
adhesion to endothelial cells and the resistance of low-
density lipoprotein (LDL) to oxidation was greatest during
the MUFA period (Fig. 1) [46].
Besides basic studies, several pre-clinical and clinical
trials have also reported the beneficial effects of OA
consumption in the immune response, especially in
autoimmune diseases. By evaluating the effects of fish oil on
the severity and progression of active human RA, Kremer et
al. observed that olive oil, used as a placebo in these
experiments, had unexpected beneficial effects on the
improvement of clinical aspects of the disease, once this
treatment was associated to decreased macrophage IL-1
production after stimulation with Con A, although not to the
same extent as to the fish oil group supplemented with EPA
or DHA [25]. Linos et al. [24] also demonstrated some
beneficial anti-inflammatory effects of OA consumption on
RA, comparing the relative risk of disease development in
relation to lifelong consumption of olive oil (almost every
day) in a Greek population. This population was four times
less likely to develop RA when compared to those who
consumed olive oil less than six times per month [24]. In
recent years olive oil/OA has been experimentally used to
treat inflammatory bowel disease (IBD) induced experimentally
by dextran sodium sulphate (DSS). Borniquel et al. [47] by
giving OA and a nitrated oleic acid (OA-NO2) subcutaneously
to DSS treated mice observed both in vitro and in v ivo the
Oleic Acid in Health and Disease Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 3
ability of OA-NO2, better than OA, to improve inflammation
and clinical score in this experimen tal intestinal
inflammation (Fig. 1). It is important to note that OA-NO2 is
a product of unsaturated fatty acids, known as nitroalkene,
that is endogenously produced [48, 49] and has anti-
inflammatory properties due to its interactions with numerous
pathways such as nuclear factor-B (NF-B) or signal
transducer and activator of transcription (STAT) [50].
Nitroalkene was already described as a strong activator of
peroxisome proliferator-activated receptor (PPAR ) in
IBD [51]. In another study in which mice were fed different
oils it was observed a lower mortality, lower clinical/
macroscopic intestinal inflammation score and a reduction in
the activity of COX-2 and iNOS in olive oil fed group, when
compared to sunflower oil fed mice [52]. Altogether, these
findings indicate that olive oil or OA present well-defined
anti-inflammatory effects on autoimmune and chronic
inflammatory diseases.
HEALING OF CUTANEOUS WOUNDS
Tissue wounds also trigger various cellular events based
on inflammation like cell migration, angiogenesis,
extracellular matrix deposition and re-epithelialization [53].
Thereby, many biological mediators are necessary to control
these different processes, like nitric oxide (NO), which is
important to skin wound healing since it influences the
functions of fibroblasts, macrophages and keratinocytes during
the healing process [54]. Inhibition of NO synthesis induces
the release of some mediators by fibroblasts and inflammatory
cells which then causes the reduction on collagen deposition
at the site of the wound [55].
Fig. (1). Summary of oleic acid (OA) effects and actions. Highlighted in black are conditions in which OA acts as enhancer such as in wound
closure or drugs absorption. In light grey, the effects of oleic acid in the reduction of inflammation, modulation of leukocytes activity,
enhancement of bactericidal and fungicidal action, inhibition of cancer proliferation and oncogenes expression, reduction of blood pressure
and attenuation of the effects of autoimmune diseases. Note that the real role of OA in leukocytes activity is still a matter of debate.
4 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 Sales-Campos et al.
MUFA and PUFA can be therapeutically used as an
option to treat cutaneous wounds. Regarding NO, OA
treatment inhibited its early production in contrast to -6 and
-3, which induced higher levels of NO in experimental skin
wounds, respectively, at 48h and 3h post surgery [56]. These
authors also demonstrated that after 5 and 10 days of
treatment of surgically induced skin wounds in mice, the
group treated with OA showed smaller wounds area mainly
when compared to -3 treated group (Fig. 1). Moreover the
OA and the -6 groups had less edema at 48 hours when
compared to control. On the other hand, after 5 days of
treatment, the -3 group showed greater edema and thicker
clot cover than -6 or OA treated groups. The treatment with
-3 induced increased amount of connective tissue fibers
deposition in the wounds site, although OA favored tissue
repair [56].
More recently, Cardoso et al. [57] demonstrated in
BALB/c mice with surgically induced skin wounds, that at
120 h after surgery there was faster wound closure, elevated
levels of collagen III mRNA, tissue inhibitor of metalloproteinase
(TIMP1) and metalloproteinases-9 (MMP9) in OA treated
group in comparison to -3 and control groups. Moreover in
OA group there were lower levels of cyclooxygenase-2
(COX-2) expression, which is important for the production
of pro-inflammatory mediators, when compared to -3
treated wounds. The OA treated group also presented an
increased gene transcription for TNF-, IL-10 and IL-17
when compared to -3 and control groups, especially at 120
h post surgery. The wound inflammatory infiltrate was also
investigated and there was a less prominent detection of
CD11b+, CD4+ and CD8+ cells in OA treated group [57],
thus demonstrating that this MUFA may actually influence
the skin inflammatory process and thus wound repair.
Additionally, another study showed that OA exerts pro-
inflammatory effects on wound healing as observed by
increased neutrophil migration to the lesions, protein and
DNA contents, besides the stimulation of mediators release
by neutrophils such as VEGF- and IL-1, thus accelerating
the wound healing process [58]. This same group showed
recently that oral administration of OA to rats with skin
wounds led to an initial NF-kB activation and increased
TNF- production 1h after tissue injury with a reduction in
pro-inflammatory cytokines 24h later, suggesting an
acceleration of the inflammatory phase of wound healing
after OA oral administration [59]. Therefore, these studies
suggest that OA modulate or have a beneficial effect on
wound closure that is an inflammation-dependent phenomenon.
OLEIC AC ID IN THE IMMUNE R ESPONS E TO
INFECTIOUS AGENTS
The effects of OA in the immunomodulation of infectious
diseases are far less investigated than those from other fatty
acids like PUFA. Even though, several studies have tried to
elucidate the possible benefits of olive oil intak e on infectious
events [60-64]. It is known that the cytokines released during
an infectious or inflammatory response, apart from modulation
of the immune system, bring about enhanced lipolysis,
gluconeogenesis, muscle proteolisis and redistribution of
tissue zinc in order to provide substrate for cells of the
immune system and amino acids for the synthesis of acute-
phase proteins [21]. However, although excess inflammatory
reactions may help in the pathogen elimination, it can also
lead to extensive tissue damage.
Regarding the putative immunomodulatory actions of
fatty acids, some studies have investigated the inflammatory
response to TNF- administration or to Escherichia coli
endotoxin in rats previously treated with corn, fish, coconut,
olive oils or butter (rich in OA). The results demonstrated
that especially in groups treated with OA, a suppression in
tissue zinc content, liver protein synthesis and serum
ceruloplasmins levels was achieved when compared to a
corn oil diet or standard laboratory chow [19, 21].
Listeria monocytogenes is a gram-positive facultative
intracellular bacterium that can cause severe infections,
especially in immunocompromised hosts, pregnant women,
newborns and elderly, reaching mortality rate of 20% or
higher. The murine infection with L. monocytogenes is a
well-characterized model for understanding cellular
immunity against intracellular bacteria [65, 66]. Puer tollano
et al. [67] demonstrated in mice experimentally infected with
Listeria monocytogenes and fed a diet rich in olive oil a
better immune response to this bacteria as well as a faster
elimination of the infectious agent along with a lower
mortality rate when compared to a group that had received
fish oil. They also demonstrated an improved macrophage
capability to destroy these pathogens in the olive oil group
(Fig. 1). Moreover, when these animals were reinfected with
Listeria monocytogenes the secondary immune response in
olive oil group was more effective than in fish oil treated-mice
[67]. Additionally, mice infected with L. monocytogenes,
which uses spleen as a supportive environment to survival
[68] and fed fish oil presented a significant increase in spleen
weight at 72 hours after secondary infection, whereas there
was a significant decrease in the olive oil fed group at the
same period evaluated [66]. It was also observed elevated
levels of serum ICAM-1 and VCAM-1 in mice experimentally
reinfected with Lysteria monocytogenes and fed olive oil or
high oleic sunflower oil when compared to fish oil fed
group. These results could suggest a relevant effect of olive
oil in the spleen leukocyte accumulation or bacteria clearance,
in comparison to other dietary fats. In addition, another study
demonstrated that olive oil presents bactericidal activity
against Helicobacter pylori, the main causative agent of
gastric ulcers which may also be related to gastric cancers
development [69].
Considering fungal infections, mice submitted to
isolation stress showed a temporarily delayed clearance of
Paracoccidioides brasiliensis, especially when their diets
were enriched in olive oil in comparison to soybean oil [70].
Thereby, olive oil seems to be less effective in the attenuation of
the stress-induced effects on host defense against this fungus
than soybean oil. It is important to note that psychological
stress, just as the isolation stress, is related to alterations in
many aspects of immune response, such as decreased activity of
natural killer (NK) cells, increased metastasis of tumors
transplanted into mice [71], reduced mitogen-stimulated
lymphocytes proliferation and abnormal production of
cytokines by these cells [72].
Besides modulating cell fatty acid content and
paracoccidioidomycosis, dietary lipids can alter innate
Oleic Acid in Health and Disease Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 5
immune functions that are also essential to pathogens
control. Monocytes and macrophages are able to phagocyte
microorganisms and kill them as an important first line cell
defense [73]. In this context, Martins de Lima-Salgado et al.
[74] observed that high OA content in vitro can increase the
fungicidal capability of macrophages infected with Candida
albicans when compared to other fatty acids such as palmitic
acid and linoleic acid. The authors also demonstrated that
OA induces a sustained effect on reactive oxygen species
(ROS) production and this may be related to the increased
fungicidal activity observed in cells treated with OA.
Overall, the findings above suggested that OA may be
beneficial to patients suffering from diseases that require a
more efficient pathogen control, such as in bacteria or fungal
infections (Fig. 1).
EFFECTS OF OLEIC ACID ON CANC ER
Different epidemiological surveys pointed to the lower
incidence of cancer occurrence in Mediterranean when
compared to Scandinavian countries, the United Kingdom
and the United States, especially those that involve the
intestine, breast, endometrium, skin and prostate [75-79].
One of the most important find ings related to such
observations was associated to Mediterranean dietary habits,
especially the low consumption of meat and high consumption
of fruits, vegetables and mainly olive oil, rich in OA [80].
Furthermore, high OA and olive oil consumption was already
associated to a reduction in the cancer risk development
(mainly breast, colorectal and prostate cancer) (Fig. 1), while
diets rich in total fat and linoleic acid or saturated fatty acid
were related to an increased cancer risk [81].
Llor and Plons [82] developed some in vitro studies to
evaluate the effect of olive oil and/or OA on colorectal
cancer cells and found that olive oil induced apoptosis, cell
differentiation and down regulated the expression of COX-2
and Bcl-2 (Fig. 1), which are associated to inflammation and
apoptosis. It was not demonstrated that OA has direct effects
on COX-2 or Bcl-2 in this study, but the authors showed a
specific induction of apoptosis in HT-29 cells [82]. Olive oil
consumption also influences the initiation, promotion and
progression of carcinogenesis and in these cases tumors
achieved a lower degree of clinical and histopathological
malignancy [83, 84]. In accordance, OA was demonstrated to
play an important chemoprotection role on breast cancer cell
lines. The in vitro treatment of breast cancer cells with OA
suppressed the oncogene Her-2/neu expression that is
overexpressed in approximately 20% of breast carcinomas
and encode the oncoprotein p185 Her-2/neu which controls,
in normal cellular conditions, many cell functions such as
cell differentiation, proliferation and apoptosis. A
deregulation on this protein expression enhances the risk of
cancer development. Moreover, the OA capability to act
synergistically with the monoclonal antibody trastuzumab,
used as a therapeutical drug on cancer by targeting p185
Her-2/neu, was already described by Menendez et al. [85].
INFLUENCE OF OLEIC ACID ON NUTRITION AND
METABOLISM
Some patients, mainly those who are hospitalized and
require intravenous nutrition therapy need adequate energy
sources which may be provided by essential fatty acids, thus
preventing metabolic disturbances associated to intravenous
feeding of amino acids and glucose [86-88]. The first well-
tolerated lipid emulsion was based on soybean oil, which is
composed mainly by -6 PUFA (linoleic acid) [33]. This
emulsion showed significant immunomodulatory effects in
patients treated with parenteral nutrition then increasing their
susceptibility to infection [61, 89-93]. One possible
mechanism by which lipid emulsion can cause these side
effects may be the induction of leukocyte death [94-97].
Therefore, other lipid emulsions did not induce this
immunosuppressive effect and constituted an alternative to
intravenous emulsion content. Thus, although many reports
point to the modulatory role of OA on the immune system as
discussed before, emulsions containing olive oil have been
suggested to offer an immunologically neutral alternative to
soybean emulsion for use in parenteral nutrition [35, 41-43,
98, 99].
On the other hand, one of the most important cytokines
usually found in metabolic inflammatory process is TNF-,
which is produced by a wide range of leukocytes in
inflammatory conditions, as well as by the adipose tissue
cells. This cytokine is thought to play a central role in the
metabolic syndrome development, which is characterized by
the presence of three or more metabolic disorders, such as
high blood glucose, low high-density lipoprotein cholesterol
(HDL-c), high blood pressure, high serum triglycerides (TG)
levels and abdominal obesity [100-103]. In this case, TNF-
leads to increased insulin peripheral resistance, inhibition of
its secretion and promotion of inflammation [104-110]. A
positive correlation between increased TNF- in type I I
diabetes patients and the development of inflammatory
process in muscle fibers was already demonstrated in
skeletal muscle biopsies [111]. In this context, the potential
of OA to exert pleiotropic effects such as the induction of
insulin production and inhibition of TNF- action was
demonstrated by in vitro studies using a rat pancreatic cell
lineage which displays glucose dependent insulin secretion
(INS-1 cells), in response to a culture medium containing
high glucose levels [112]. The molecular mechanism by
which OA exerted its role in the reversion of TNF- action is
quite varied and PPAR- receptor may be involved, since it
is known that fatty acids and its metabolites are activators of
PPAR-, besides being able to ameliorate the inflammatory
effects of TNF- [1]. Furthermore the translocation of
PPAR- to the nucleus is though to mediate the anti-
inflammatory properties of fatty acids [112]. Thus, OA may
present potential applications and benefits in human health
regarding the prevention of metabolic and nutrition
disturbances in a selective group of patients.
BLOOD PRESSURE AND CARDIOVASCULAR
DISEASES
The protective action of OA regular intake on health risk
parameters, especially in cardiovascular disease, is mainly
reported in the Mediterranean area, where people’s diet is
associated to elevated MUFA intake due to higher
consumption of olive oil [113, 114]. So far, the potential of
OA to ameliorate cardiovascular risks may be associated to
an improvement of serum lipoprotein profile (HDL-to-LDL)
in patients with hypercholesterolemia [115, 116], besides an
6 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 Sales-Campos et al.
enhanced endothelial function due to an increase in flow-
associated vasodilatation in hypercholesterolemic patients
[117] and reduction in inflammation and oxidative stress
[118]. Subsequently, there is a diminishment in the anti-
hypertensive drugs consumption and in the occurrence of
degenerative diseases [119-123] together with a better blood
pressure control both in humans [124] and rats fed a diet rich
in OA (Fig. 1) [125, 126].
The and adrenergic receptors are essential in
controlling central and peripheral blood pressure and these
pathways can be regulated by OA [127] because of its effects
on cell membrane structures [127, 128]. For some time, the
action of olive oil on blood pressure control was considered
to be due to the properties of less representative compounds
of this oil such as -tocopherol, polyphenols and other
phenolic substances [23, 129-132]. However, Terés et al.
[14] demonstrated in vivo , that the high OA content in olive
oil and not its minor compounds, are responsible for the
normotensive effects attributed to olive oil consumption,
both in chronic and acute experimental treatments using
olive oil (Fig. 1) [14]. Furthermore, this MUFA may act
through modulation of membrane lipid structures and cell
signaling platforms, with additional regulation of the 2-
adrenergic receptor pathways that involve G protein-
dependent signaling and results in blood pressure control
[127]. Then, the specific molecular mechanism by which OA
controls blood pressure involves its ability to modulate the
structure of plasma membrane lipids due to a regulatory
pathway associated to the inhibition of G proteins both in
vivo (in humans) and in vitro (cell culture) [127, 133].
Indeed, higher levels of MUFA on cell membrane can
regulate the localization, activity and the expression of other
important signaling molecules raising the production of
vasodilator stimuli (cAMP and PKA) and reducing the action
of vasoconstrictor pathways (inositol-triphosphate, Ca+2,
diacylglycerol and Rho kinases) [133]. To date, membrane
lipids and G proteins levels are altered in experimental
models [134, 135] and in hypertensive subjects [136, 137],
especially after a long-term exposure to olive oil diet [138].
Fibrinogen higher levels have already been described as
an independent cardiovascular risk factor [139] due to its
association to the inflammatory process, initiation of
atherogenesis and growth of atheromatous lesions [140].
Likewise, elevated fibrinogen was reported in coronary,
cerebral disease and peripheral arteries [141]. Then, in a
double-blind crossover study, Oosthuizen et al. (1994)
reported a lowering of plasma fibrinogen levels in women
who received fish or olive oils with high baseline fibrinogen
concentrations [142]. Conversely, another study reported no
significant difference between fish oil supplements and an
olive oil placebo in preventing restenosis after coronary
angioplasty [143].
CELL MEMBRANE FLUIDITY AND CUTANEOUS
EFFECT ON DRUGS ABSORPTION
Fatty acids in general can change the cell membrane
fluidity as well as its surface receptors. Several cell surface
proteins form complex with cell membrane receptors and as
a consequence, many cell functions like those mediated by
MHC expression or cell adhesion molecules are regulated.
Then, the initial events of cellular activation and signal
transduction in specialized cells, including leukocytes, occur
in cell membrane defined areas called lipid rafts [67]. Lipid
rafts are cellular membrane areas composed by sphingolipids
and cholesterol phospholipids [144]. This area acts as an
exclusive site that helps receptors to function and trigger or
sustain cell activation (intracellular signaling pathways) [67],
influen ce on the entry of pathogen in the cell and cytoskeletal
organization [145]. Shaikh et al. [146] suggested that
unsaturated fatty acids may affect lipid raft structure and
function by modifying lipid separations [146]. In addition,
Ehehalt et al. [147] demonstrated that FA uptake is closely
related and depends on lipid rafts integrity. These authors
also showed a close relationship between lipid raft cholesterol
content and FA levels observing an inhibition of FA uptake
greater than 50% by decreasing cellular cholesterol levels
[147].
Alternative routes to oral or systemic treatment of a wide
range of diseases, especially those that require the use of
anti-inflammatory drugs are of great interest due to the
occurrence of hepatic or systemic side effects [148]. In this
context, Moreira et al., showed that OA enhances (Fig. 1) the
skin distribution and penetration of Lumiracoxib, by
increasing its local retention both in dermis and epidermis,
thus leading to a gradual and dose dependent drug absorption.
To note, Lumiracoxib is a selective non-steroidal anti-
inflammatory (NSAI) drug developed for the management of
chronic and acute pain through the inhibition of COX-2
activities [149]. Furthermore, El Maghraby et al.
demonstrated that OA h as the ability to penetrate on stratum
corneum by disrupting the intercellular lipid structures [150],
a fact that could explain its action on skin physiology and
drugs absorption.
By investigating the role of OA on NSAI drugs
absorption, others observed that these FA, when administrated
as patches in a membrane controlled transdermal drug
delivery system, may provide the maximum permeability
capacity to ketoprofen when compared to other permeation
enhancers such as polyethylene glycol 400 and propylene
glycol [151]. On the other hand, Santoyo & Yqartua using
piroxicam, which is also classified as a NSAI, showed that a
skin pretreated with OA has adequate drug absorption but
not better than linolenic acid pretreated skin. In addition,
despite the retention of drugs into the skin they demonstrated
that FA pretreatment, with no differences between them,
retains 3 times more drug than no pretreated skin [152].
Similarly, Larrucea et al. (2001) showed an enhanced
capability of OA to improve percutaneous permeability to
tenoxicam after skin pretreatment [153]. These data are in
agreement with those from mice studies, in which Gwak &
Chun (2002) observed and enhanced capability of OA to
improve permeability to tenoxicam [154]. Moreover, OA
when associated to diclofenac induced a higher permeation-
enhancing effect than that induced by saturated fatty acids
such as palmitic acid in rats skin [155].
CONCLUSION
In summary, this review demonstrated that OA, which is
naturally found in olive oil and is a major component of the
Mediterranean diet, presents different properties that can be
Oleic Acid in Health and Disease Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 7
useful both in the immunomodulation, treatment and
prevention of different types of disorders such as cardiovascular
or autoimmune diseases, metabolic disturbances, skin injury
and cancer, besides exerting proeminent role in drug
absorption. However, further studies are still necessary and
should be conducted in order to better clarify the properties
of this fatty acid in human health and disease, as well as to
provide scientific basis for the future establishment of novel
therapeutic approaches for such disorders based on this
MUFA.
CONFLICT OF INTEREST
The authors confirm that this article content has no
conflicts of interest.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Burr, G.O.; Burr, M.M. A new deficiency disease produced by rigid
exclusion of fat from thediet. J Biol Chem., 1929, 82, 345-367.
[2] Hansen, A.E.; Wiese, H.F.; Boelsche, A.N.; Haggard, M.E.; Adam,
D.J.D.; Davis, H. Role of linoleic acid in infant nutrition: clinical
and chemical study of 428 infants fed on milk mixtures varying in
kind and amount of fat. Pediatrics, 1963, 31, 171-192.
[3] Caldwell, M.D.; Jonsson, H.T.; Othersen, H.B., Jr. Essential fatty
acid deficiency in an infant receiving prolonged parenteral
alimentation. J Pediatr., 1972, 81, 894-898.
[4] Paulsrud, J.R.; Pensler, L.; Whitten, C.F.; Stewart, S.; Holman,
R.T. Essential fatty acid deficiency in infants induced by fat-free
intravenous feeding. Am J Clin Nutr., 1972, 25, 897-904.
[5] Miles, E.A.; Calder, P.C. Modulation of immune function by
dietary fatty acids. Proc Nutr Soc., 1998, 57, 277-292.
[6] Gunstone, F.D. High resolution 13C NMR. A technique for the study of
lipid structure and composition. Prog Lipid Res., 1994, 33, 19-28 .
[7] Hornstra, G. In Biochemical physiology of dietary fats; Martinus
Nijhoff Publishers: Boston, 1982, 15-29.
[8] Yaqoob, P. Monounsaturated fatty acids and immune function. Eur
J Clin Nutr., 2002, 56 Suppl 3, S9-S13.
[9] Trichopoulou, A.; Kouris-Blazos, A.; Wahlqvist, M.L.; Gnardellis,
C.; Lagiou, P.; Polychronopoulos, E.; Vassilakou, T.; Lipworth, L.;
Trichopoulos, D. Diet and overall survival in elderly people. BMJ,
1995, 311, 1457-1460.
[10] Owen, R.W.; Mier, W.; Giacosa, A.; Hull, W.E.; Spiegelhalder, B.;
Bartsch, H. Phenolic compounds and squalene in olive oils: the
concentration and antioxidant potential of total phenols, simple
phenols, secoiridoids, lignansand squalene. Food Chem Toxicol.,
2000, 38, 647-659.
[11] Jossa, F.; Mancini, M. [The Mediterranean diet in the prevention of
arteriosclerosis]. Recenti Prog Med., 1996, 87, 175-181.
[12] Tsimikas, S.; Reaven, P.D. The role of dietary fatty acids in
lipoprotein oxidation and atherosclerosis. Curr Opin Lipidol., 1998,
9, 301-307.
[13] Panagiotakos, D.B.; Dimakopoulou, K.; Katsouyanni, K.; Bellander, T.;
Grau, M.; Koenig, W .; Lanki, T.; Piste lli, R.; Schneider, A.; Peter s, A.
Mediterranean diet and inflammatory response in myocardial infarction
survivors. Int J Epidemio l., 2009, 38, 856-866.
[14] Teres, S.; Barcelo-Coblijn, G.; Benet, M.; Alvarez, R.; Bressani,
R.; Halver, J.E.; Escriba, P.V. Oleic acid content is responsible for
the reduction in blood pressure induced by olive oil. Proc Natl
Acad Sci U S A., 2008, 105, 13811-13816.
[15] Bersamin, A.; Luick, B.R.; King, I.B.; Stern, J.S.; Zidenberg-Cherr,
S. Westernizing diets influence fat intake, red blood cell fatty acid
composition, and health in remote Alaskan Native communities in
the center for Alaska Native health study. J Am Diet Assoc., 2008,
108, 266-273.
[16] Lardinois, C.K. The role of omega 3 fatty acids on insulin secretion
and insulin sensitivity. Med Hypotheses, 1987, 24, 243-248.
[17] Mulvad, G.; Pedersen, H.S.; Hansen, J.C.; Dewailly, E.; Jul, E.;
Pedersen, M.; Deguchi, Y.; Newman, W.P.; Malcom, G.T.; Tracy,
R.E.; Middaugh, J.P.; Bjerregaard, P. The Inuit diet. Fatty acids and
antioxidants, their role in ischemic heart disease, and exposure to
organochlorines and heavy metals. An international study. Arctic
Med Res., 1996, 55, 20-24.
[18] Drosos, A.A.; Moutsopoulos, H.M. Rheumatoid arthritis in Greece:
clinical, serological and genetic considerations. Clin Exp
Rheumatol., 1995, 13, 7-12.
[19] Besler, H.T.; Grimble, R.F. Comparison of the modulatory
influence of maize and olive oils and butter on metabolic responses
to endotoxin in rats. Clin Sci (Lond)., 1995, 88, 59-66.
[20] Yaqoob, P. Monounsaturated fats and immune function. Braz J
Med Biol Res., 1998, 31, 453-465.
[21] Mulrooney, H.M.; Grimble, R.F. Influence of butter and of corn,
coconut and fish oils on the effects of recombinant human tumour
necrosis factor-alpha in rats. Clin Sci (Lond)., 1993, 84, 105-112.
[22] Sanderson, P.; Yaqoob, P.; Calder, P.C. Effects of dietary lipid
manipulation upon graft vs host and host vs graft responses in the
rat. Cell Immunol., 1995, 164, 240-247.
[23] Ferrara, L.A.; Raimondi, A.S.; d'Episcopo, L.; Guida, L.; Dello Russo,
A.; Marotta, T. Olive oil and reduced need for antihypertensive
medications. Arch Intern Med., 2000, 160, 837-842.
[24] Linos, A.; Kaklamanis, E.; Kontomerkos, A.; Koumantaki, Y.;
Gazi, S.; Vaiopoulos, G.; Tsokos, G.C.; Kaklamanis, P. The effect
of olive oil and fish consumption on rheumatoid arthritis--a case
control study. Scand J Rheumatol., 1991, 20, 419-426.
[25] Kremer, J.M.; Lawrence, D.A.; Jubiz, W.; DiGiacomo, R.; Rynes,
R.; Bartholomew, L.E.; Sherman, M. Dietary fish oil and olive oil
supplementation in patients with rheumatoid arthritis. Clinical and
immunologic effects. Arthritis Rheum., 1990, 33, 810-820.
[26] Lipworth, L.; Martinez, M.E.; Angell, J.; Hs ieh, C.C.;
Trichopoulos, D. Olive oil and human cancer: an assessment of the
evidence. Prev Med., 1997, 26, 181-190.
[27] Assmann, G.; de Backer, G.; Bagnara, S.; Betteridge, J.; Crepaldi,
G.; Fernandez-Cruz, A.; Godtfredsen, J.; Jacotot, B.; Paoletti, R.;
Renaud, S.; Ricci, G.; Rocha, E.; Trautwein, E.; Urbinati, G.C.;
Varela, G.; Williams, C. International consensus statement on olive
oil and the Mediterranean diet: implications for health in Europe.
The Olive Oil and the Mediterranean Diet Panel. Eur J Cancer
Prev., 1997, 6, 418-421.
[28] Martin-Moreno, J. M.; Willett, W.C.; Gorgojo, L.; Banegas, J.R.;
Rodriguez-Artalejo, F.; Fernandez-Rodriguez, J.C.; Maisonneuve,
P.; Boyle, P. Dietary fat, olive oil intake and breast cancer risk. Int
J Cancer, 1994, 58, 774-780.
[29] Simonsen, N.R.; Fernandez-Crehuet Navajas, J.; Martin-Moreno,
J.M.; Strain, J.J.; Huttunen, J.K.; Martin, B.C.; Thamm, M.;
Kardinaal, A.F.; van't Veer, P.; Kok, F.J.; Kohlmeier, L. Tissue
stores of individual monounsaturated fatty acids and breast cancer:
the EURAMIC study. European Community Multicenter Study on
Antioxidants, Myocardial Infarction, and Breast Cancer. Am J Clin
Nutr., 1998, 68, 134-141.
[30] Solanas, M.; Hurtado, A.; Costa, I.; Moral, R.; Menendez, J.A.;
Colomer, R.; Escr ich, E. Effects of a high olive oil diet on the
clinical behavior and histopathological features of rat DMBA-
induced mammary tumors compared with a high corn oil diet. Int J
Oncol., 2002, 21, 745-753.
[31] Calder, P.C. N-3 polyunsaturated fatty acids and inflammation:
from molecular biology to the clinic. Lipids, 2003, 38, 343-352.
[32] de Pablo, M.A.; Alvarez de Cienfuegos, G. Modulatory effects of
dietary lipids on immune system functions. Immunol Cell Biol.,
2000, 78, 31-39.
[33] Cury-Boaventura, M.F.; Gorjao, R.; de Lima, T.M.; Fiamoncini, J.;
Torres, R.P.; Mancini-Filho, J.; Soriano, F.G.; Curi, R. Effect of
olive oil-based emulsion on human lymphocyte and neutrophil
death. JPEN J Parenter Enteral Nutr., 2008, 32, 81-87.
[34] Cury-Boaventura, M.F.; Gorjao, R.; de Lima, T.M.; Piva, T.M.;
Peres, C.M.; Soriano, F.G.; Curi, R. Toxicity of a soybean oil
emulsion on human lymphocytes and neutrophils. J Parenter
Enteral Nutr., 2006, 30, 115-123.
[35] Reimund, J.M.; Rahmi, G.; Escalin, G.; Pinna, G.; Finck, G.;
Muller, C.D.; Duclos, B.; Baumann, R. Efficacy and safety of an
olive oil-based intravenous fat emulsion in adult patients on home
parenteral nutrition. Aliment Pharmacol Ther., 2005, 21, 445-454.
[36] Yaqoob, P.; Newsholme, E.A.; Calder, P.C. Inhibition of natural
killer cell activity by dietary lipids. Immunol Lett., 1994, 41, 241-247.
8 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 Sales-Campos et al.
[37] Yaqoob, P.; Newsholme, E.A.; Calder, P.C. The effect of dietary
lipid manipulation on rat lymphocyte subsets and proliferation.
Immunology, 1994, 82, 603-610.
[38] Yaqoob, P.; Newsholme, E.A.; Calder, P.C.; Phil, D. The effect of
fatty acids on leucocyte subsets and proliferation in rat whole
blood. Nutrional Research, 1995, 15, 279-287.
[39] Yaqoob, P.; Knapper, J.A.; Webb, D.H.; Williams, C.M.;
Newsholme, E.A.; Calder, P.C. Effect of olive oil on immune
function in middle-aged men. Am J Clin Nutr., 1998, 67, 129-135.
[40] Jeffery, N.M.; Cortina, M.; Newsholme, E.A.; Calder, P.C. Effects
of variations in the proportions of saturated, monounsaturated and
polyunsaturated fatty acids in the rat diet on spleen lymphocyte
functions. Br J Nutr., 1997, 77, 805-823.
[41] Moussa, M.; Le Boucher, J.; Garcia, J.; Tkaczuk, J.; Ragab, J.;
Dutot, G.; Ohayon, E.; Ghisolfi, J.; Thouvenot, J.P. In vivo effects
of olive oil-based lipid emulsion on lymphocyte activation in rats.
Clin Nutr., 2000, 19, 49-54.
[42] Garnacho-Montero, J.; Ortiz-Leyba, C.; Garnacho-Montero, M.C.;
Garcia-Garmendia, J.L.; Perez-Paredes, C.; Moyano-Del Estad,
M.R.; Barrero-Almodovar, A.; Jimenez-Jimenez, F.J. Effects of
three intravenous lipid emulsions on the survival and mononuclear
phagocyte function of septic rats. Nutrition, 2002, 18, 751-754.
[43] Buenestado, A.; Cortijo, J.; Sanz, M.J.; Naim-Abu-Nabah, Y.;
Martinez-Losa, M.; Mata, M.; Issekutz, A.C.; Marti-Bonmati, E. ;
Morcillo, E.J. Olive oil-based lipid emulsion's neutral effects on
neutrophil functions and leukocyte-endothelial cell interactions. J
Parenter Enteral Nutr., 2006, 30, 286-296.
[44] Jeffery, N.M.; Yaqoob, P.; Newsholme, E.A.; Calder, P.C. The
effects of olive oil upon rat serum lipid levels and lymphocyte
functions appear to be due to oleic acid. Ann Nutr Metab., 1996,
40, 71-80.
[45] De Caterina, R.; Cybulsky, M.I.; Clinton, S.K.; Gimbrone, M.A.,
Jr.; Libby, P. The omega-3 fatty acid docosahexaenoate reduces
cytokine-induced expression of proatherogenic and
proinflammatory proteins in human endothelial cells. Arterioscler
Thromb., 1994, 14, 1829-1836.
[46] Mata, P.; Alonso, R.; Lopez-Farre, A.; Ordovas, J.M.; Lahoz, C.;
Garces, C.; Caramelo, C.; Codoceo, R.; Blazquez, E.; de Oya, M.
Effect of dietary fat saturation on LDL oxidation and monocyte
adhesion to human endothelial cells in vitro. Arterioscler Thromb
Vasc Biol., 1996, 16, 1347-1355.
[47] Borniquel, S.; Jansson, E.A.; Cole, M.P.; Freeman, B.A. ;
Lundberg, J.O. Nitrated oleic acid up-regulates PPARgamma and
attenuates experimental inflammatory bowel disease. Free Radic
Biol Med., 2010, 48, 499-505.
[48] Rudolph, V.; Schopfer, F.J.; Khoo, N.K.; Rudolph, T.K.; Cole,
M.P.; Woodcock, S.R.; Bonacci, G.; Groeger, A.L.; Golin-Bisello,
F.; Chen, C.S.; Baker, P.R.; Freeman, B.A. Nitro-fatty acid
metabolome: saturation, desaturation, beta-oxidation, and protein
adduction. J Biol Chem., 2009, 284, 1461-1473.
[49] Baker, P.R.; Schopfer, F.J.; Sweeney, S.; Freeman, B.A. Red cell
membrane and plasma linoleic acid nitration products: synthesis,
clinical identification, and quantitation. Proc Natl Acad Sci U S A,
2004, 101, 11577-11582.
[50] Cui, T.; Schopfer, F.J.; Zhang, J.; Chen, K.; Ichikawa, T.; Baker,
P.R.; Batthyany, C.; Chacko, B.K.; Feng, X.; Patel, R.P.; Agarwal,
A.; Freeman, B.A.; Chen, Y.E. Nitrated fatty acids: Endogenous
anti-inflammatory signaling mediators. J Biol Chem., 2006, 281,
35686-35698.
[51] Dubuquoy, L.; Rousseaux, C.; Thuru, X.; Peyrin-Biroulet, L.;
Romano, O.; Chavatte, P.; Chamaillard, M.; Desreumaux, P.
PPARgamma as a new therapeutic target in inflammatory bowel
diseases. Gut, 2006, 55, 1341-1349.
[52] Sanchez-Fidalgo, S.; Sanchez de Ibarguen, L.; Cardeno, A.;
Alarcon de la Lastra, C. Influence of extra virgin olive oil diet
enriched with hydroxytyrosol in a chronic DSS colitis model. Eur J
Nutr., 2012, 51, 497-506.
[53] Clark, M.E.; Rafferty, M. The sickness that won't heal. Health care
for the nation's homeless. Health PAC Bull., 1985, 16, 20-28.
[54] Frank, S.; Kampfer, H.; Wetzler, C.; Pfeilschifter, J. Nitric oxide
drives skin repair: novel functions of an established mediator.
Kidney Int., 2002, 61, 882-888.
[55] Schaffer, M.R.; Tantry, U.; Gross, S.S.; Wasserburg, H.L.; Barbul,
A. Nitric oxide regulates wound healing. J Surg Res., 1996, 63,
237-240.
[56] Cardoso, C.R.; Souza, M.A.; Ferro, E.A.; Favoreto, S., Jr.; Pena,
J.D. Influence of topical administration of n-3 and n-6 essential and
n-9 nonessential fatty acids on the healing of cutaneous wounds.
Wound Repair Regen., 2004, 12, 235-243.
[57] Cardoso, C.R.; Favoreto, S., Jr.; Oliveira, L.L.; Vancim, J.O.;
Barban, G.B.; Ferraz, D.B.; Silva, J.S. Oleic acid modulation of the
immune response in wound healing: a new approach for skin
repair. Immunobiology, 2011, 216, 409-415.
[58] Pereira, L.M.; Hatanaka, E.; Martins, E.F.; Oliveira, F.; Liberti,
E.A.; Farsky, S.H.; Curi, R.; Pithon-Curi, T.C. Effect of oleic and
linoleic acids on the inflammatory phase of wound healing in rats.
Cell Biochem Funct., 2008, 26, 197-204.
[59] Rodrigues, H.G.; Vinolo, M.A.; Magdalon, J.; Vitzel, K.; Nachbar,
R.T.; Pessoa, A.F .; dos Santos, M.F.; Hatanaka, E.; Calder, P.C.;
Curi, R. Oral administration of oleic or linoleic acid accelerates the
inflammatory phase of wound healing. J Invest Dermatol., 2012,
132, 208-215.
[60] Kremer, J.M. n-3 fatty acid supplements in rheumatoid arthritis.
Am J Clin Nutr., 2000, 71, 349S-351S.
[61] Anderson, M.; Fritsche, K.L. (n-3) Fatty acids and infectious
disease resistance. J Nutr., 2002, 132, 3566-3576.
[62] de Pablo, M.A.; Puertollano, M.A.; Galvez, A.; Ortega, E.; Gaforio,
J.J.; Alvarez de Cienfuegos, G. Determination of natural resistance
of mice fed dietary lipids to experimental infection induced by
Listeria monocytogenes. FEMS Immunol Med Microbiol., 2000,
27, 127-133.
[63] Fritsche, K.L.; Shahbazian, L.M.; Feng, C.; Berg, J.N. Dietary fish
oil reduces survival and impairs bacterial clearance in C3H/Hen
mice challenged with Listeria monocytogenes. Clin Sci (Lond).,
1997, 92, 95-101.
[64] de Pablo, M.A.; Puertollano, M.A.; Alvarez de Cienfuegos, G.
Biological and clinical significance of lipids as modulators of immune
system functions. Clin Diagn Lab Immunol., 2002, 9, 945-950.
[65] Edelson, B.T.; Unanue, E.R. MyD88-dependent but Toll-like
receptor 2-independent innate immunity to Listeria: no role for
either in macrophage listericidal activity. J Immunol., 2002, 169,
3869-3875.
[66] Cruz-Chamorro, L.; Puertollano, E.; de Cienfuegos, G.A.;
Puertollano, M.A.; de Pablo, M.A. Acquired resistance to Listeria
monocytogenes during a secondary infection in a murine model fed
dietary lipids. Nutrition, 2011.
[67] Puertollano, M.A.; Puertollano, E.; Alvarez de Cienfuegos, G.; de
Pablo Martinez, M.A. [Olive oil, immune system and infection].
Nutr Hosp., 2010, 25, 1-8.
[68] Verschoor, A.; Neuenhahn, M.; Navarini, A.A.; Graef, P.;
Plaumann, A.; Seidlmeier, A.; Nieswandt, B.; Massberg, S.;
Zinkernagel, R.M.; Hengartner, H.; Busch, D.H. A platelet-
mediated system for shuttling blood-borne bacteria to CD8alpha+
dendritic cells depends on glycoprotein GPIb and complement C3.
Nat Immunol., 2011, 12, 1194-1201.
[69] Romero, C.; Medina, E.; Vargas, J.; Brenes, M.; De Castro, A. In
vitro activity of olive oil polyphenols against Helicobacter pylori. J
Agric Food Chem., 2007, 55, 680-686.
[70] Oarada, M.; Igarashi, M.; Tsuzuki, T.; Kurita, N.; Gonoi, T.;
Nikawa, T.; Hirasaka, K.; Miyazawa, T.; Nakagawa, K.; Kamei, K.
Effect of dietary oils on host resistance to fungal infection in
psychologically stressed mice. Biosci Biotechnol Biochem., 2009,
73, 1994-1998.
[71] Wu, W.; Yamaura, T.; Murakami, K.; Murata, J.; Matsumoto, K.;
Watanabe, H.; Saiki, I. Social isolation stress enhanced liver
metastasis of murine colon 26-L5 carcinoma cells by suppressing
immune responses in mice. Life Sci., 2000, 66, 1827-1838.
[72] Oarada, M.; Gonoi, T.; Tsuzuki, T.; Igarashi, M.; Hirasaka, K.;
Nikawa, T.; Onishi, Y.; Toyotome, T.; Kamei, K.; Miyazawa, T.;
Nakagawa, K.; Kashima, M.; Kurita, N. Effect of dietary oils on
lymphocyte immunological activity in psychologically stressed
mice. Biosci Biotechnol Biochem., 2007, 71, 174-182.
[73] Adams, D.H., TA. In The Natural Immune System: The
Macrophage. Lewis, C.M., JOD, Ed.; Oxford: IRL Press: OXford,
1992, 75-105.
[74] Martins de Lima-Salgado, T.; Coccuzzo Sampaio, S.; Cury-
Boaventura, M.F.; Curi, R. Modulatory effect of fatty acids on
fungicidal activity, respiratory burst and TNF-alpha and IL-6
production in J774 murine macrophages. Br J Nutr., 2011, 105,
1173-1179.
Oleic Acid in Health and Disease Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 9
[75] Trichopoulou, A.; Lagiou, P.; Kuper, H.; Trichopoulos, D. Cancer
and Mediterranean dietary traditions. Cancer Epidemiol
Biomarkers Prev., 2000, 9, 869-873.
[76] Harwood, J.L., Yaqoob, P. Nutritional and health aspects of olive
oil. European Journal of Lipid and Science Technology, 2002, 104,
685-697.
[77] Keys, A.; Menotti, A.; Karvonen, M.J.; Aravanis, C.; Blackburn,
H.; Buzina, R.; Djordjevic, B.S.; Dontas, A.S.; Fidanza, F.; Keys,
M.H.; et al. The diet and 15-year death rate in the seven countries
study. Am J Epidemiol., 1986, 124, 903-915.
[78] Owen, R.W.; Giacosa, A.; Hull, W.E.; Haubner, R.; Wurtele, G.;
Spiegelhalder, B.; Bartsch, H. Olive-oil consumption and health:
the possible role of antioxidants. Lancet Oncol., 2000, 1, 107-112.
[79] Owen, R.W.; Haubner, R.; Wurtele, G.; Hull, E.; Spiegelhalder, B.;
Bartsch, H. Olives and olive oil in cancer prevention. Eur J Cancer
Prev., 2004, 13, 319-326.
[80] Trichopoulou, A.; Lagiou, P. Healthy traditional Mediterranean
diet: an expression of culture, history, and lifestyle. Nutr Rev.,
1997, 55, 383-389.
[81] Binukumar, B.; Mathew, A. Dietary fat and risk of breast cancer.
World J Surg Oncol., 2005, 3, 45.
[82] Llor, X.; Pons, E.; Roca, A.; Alvarez, M.; Mane, J.; Fernandez-
Banares, F.; Gassull, M.A. The effects of fish oil, olive oil, oleic
acid and linoleic acid on colorectal neoplastic processes. Clin Nutr.,
2003, 22, 71-79.
[83] Escrich, E.; Solanas, M.; Moral, R.; Costa, I .; Grau, L. Are the
olive oil and other dietary lipids related to cancer? Experimental
evidence. Clin Transl Oncol., 2006, 8, 868-883.
[84] Costa, I.; Moral, R.; Solanas, M.; Escrich, E. High-fat corn oil diet
promotes the development of high histologic grade rat DMBA-
induced mammary adenocarcinomas, while high olive oil diet does
not. Breast Cancer Res Treat., 2004, 86, 225-235.
[85] Menendez, J.A.; Vellon, L.; Colomer, R.; Lupu, R. Oleic acid, the main
monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2)
expression and synergistically enhances the growth inhibitory effects of
trastuzumab (Herceptin) in breast cancer cells with Her-2/neu oncogene
amplifica tion. Ann Oncol., 2005, 16, 359-371.
[86] Hansen, L.M.; Hardie, B.S.; Hidalgo, J. Fat emulsion for
intravenous administration: clinical experience with intralipid 10%.
Ann Surg., 1976, 184, 80-88.
[87] Waitzberg, D.L.; Torrinhas, R.S.; Jacintho, T.M. New parenteral
lipid emulsions for clinical use. J Parenter Enteral Nutr., 2006, 30,
351-367.
[88] Huschak, G.; Zur Nieden, K.; Hoell, T.; Riemann, D.; Mast, H.;
Stuttmann, R. Olive oil based nutrition in multiple trauma patients:
a pilot study. Intensive Care Med., 2005, 31, 1202-1208.
[89] Fischer, G.W.; Hunter, K.W.; Wilson, S.R.; Mease, A.D. Diminished
bacterial defences with intralipid. Lancet, 1980, 2, 819-820.
[90] Freeman, J.; Goldmann, D.A.; Smith, N.E.; Sidebottom, D.G.;
Epstein, M.F.; Platt, R. Association of intravenous lipid emulsion
and coagulase-negative staphylococcal bacteremia in neonatal
intensive care units. N Engl J Med., 1990, 323, 301-308.
[91] Muller, J.M.; Keller, H.W.; Brenner, U.; Walter, M.; Holzmuller,
W. Indications and effects of preoperative parenteral nutrition.
World J Surg., 1986, 10, 53-63.
[92] Sosenko, I.R.; Rodriguez-Pierce, M.; Bancalari, E. Effect of early
initiation of intravenous lipid administration on the incidence and
severity of chronic lung disease in premature infants. J Pediatr.,
1993, 123, 975-982.
[93] Battistella, F.D.; Widergren, J.T.; Anderson, J.T.; Siepler, J.K. ;
Weber, J.C.; MacColl, K. A prospective, randomized trial of
intravenous fat emulsion administration in trauma victims requiring
total parenteral nutrition. J Trauma., 1997, 43, 52-58;
[94] Cury-Boaventura, M.F.; Gorjao, R.; de Lima, T.M.; Newsholme,
P.; Curi, R. Comparative toxicity of oleic and linoleic acid on
human lymphocytes. Life Sci., 2006, 78, 1448-1456.
[95] Cury-Boaventura, M.F.; Pompeia, C.; Curi, R. Comparative
toxicity of oleic acid and linoleic acid on Jurkat cells. Clin Nutr.,
2004, 23, 721-732.
[96] Cury-Boaventura, M.F.; Pompeia, C.; Curi, R. Comparative
toxicity of oleic acid and linoleic acid on Raji cells. Nutrition,
2005, 21, 395-405.
[97] Martins de Lima, T.; Cury-Boaventura, M.F.; Giannocco, G.;
Nunes, M.T.; Curi, R. Comparative toxicity of fatty acids on a
macrophage cell line (J774). Clin Sci (Lond)., 2006, 111, 307-317.
[98] Wanten, G. An update on parenteral lipids and immune function:
only smoke, or is there any fire? Curr Opin Clin Nutr Metab Care,
2006, 9, 79-83.
[99] Granato, D.; Blum, S.; Rossle, C.; Le Boucher, J.; Malnoe, A.;
Dutot, G. Effects of parenteral lipid emulsions with different fatty
acid composition on immune cell functions in vitro. JPEN J
Parenter Enteral Nutr., 2000, 24, 113-118.
[100] NIH; NIH - National Institute of Health: Bethesda-Md, 2001.
[101] Reaven, G.M. Banting lecture 1988. Role of insulin resistance in
human disease. Diabetes, 1988, 37, 1595-1607.
[102] Alberti, K.G.; Zimmet, P.Z. Definition, diagnosis and classification
of diabetes mellitus and its complications. Part 1: diagnosis and
classification of diabetes mellitus provisional report of a WHO
consultation. Diabet Med., 1998, 15, 539-553.
[103] Grundy, S.M.; Brewer, H.B., Jr.; Cleeman, J.I.; Smith, S.C., Jr.;
Lenfant, C. Definition of metabolic syndrome: report of the
National Heart, Lung, and Blood Institute/American Heart
Association conference on scientific issues related to definition.
Arterioscler Thromb Vasc Biol., 2004, 24, e13-18.
[104] Catalan, V.; Gomez-Ambrosi, J.; Ramirez, B.; Rotellar, F.; Pastor,
C.; Silva, C.; Rodriguez, A.; Gil, M.J.; Cienfuegos, J.A.; Fruhbeck,
G. Proinflammatory cytokines in obesity: impact of type 2 diabetes
mellitus and gastric bypass. Obes Surg., 2007, 17, 1464-1474.
[105] Lichtenstein, A.H.; Ausman, L.M.; Carrasco, W.; Jenner, J.L.; Ordovas,
J.M.; Schaefer, E.J. Hydrogenation impairs the hypolipidemic effect of
corn oil in humans. Hydrogenation, trans fatty acids, and plasma lipids.
Arterioscler Thromb., 1993, 13, 154-161.
[106] Kim, H.E.; Choi, S.E.; Lee, S.J.; Lee, J.H.; Lee, Y.J.; Kang, S.S.;
Chun, J.; Kang, Y. Tumour necrosis factor-alpha-induced glucose-
stimulated insulin secretion inhibition in INS-1 cells is ascribed to a
reduction of the glucose-stimulated Ca2+ influx. J Endocrinol.,
2008, 198, 549-560.
[107] Yudkin, J.S. Inflammation, obesity, and the metabolic syndrome.
Horm Metab Res., 2007, 39, 707-709.
[108] Vassiliou, E.; Jing, H.; Ganea, D. Prostaglandin E2 inhibits TNF
production in murine bone marrow-derived dendritic cells. Cell
Immunol., 2003, 223, 120-132.
[109] Zhang, S.; Kim, K.H. TNF-alpha inhibits glucose-induced insulin
secretion in a pancreatic beta-cell line (INS-1). F EBS Lett., 1995,
377, 237-239.
[110] del Aguila, L.F.; Claffey, K.P.; Kirwan, J.P. TNF-alpha impairs
insulin signaling and insulin stimulation of glucose uptake in
C2C12 muscle cells. Am J Physiol., 1999, 276, 849-855.
[111] Plomgaard, P.; Nielsen, A.R.; Fischer, C.P.; Mortensen, O.H.;
Broholm, C.; Penkowa, M.; Krogh-Madsen, R.; Erikstrup, C.;
Lindegaard, B.; Petersen, A.M.; Taudorf, S.; Pedersen, B.K.
Associations between insulin resistance and TNF-alpha in plasma,
skeletal muscle and adipose tissue in humans with and without type
2 diabetes. Diabetologia, 2007, 50, 2562-2571.
[112] Vassiliou, E.K.; Gonzalez, A.; Garcia, C.; Tadros, J.H.;
Chakraborty, G.; Toney, J.H. Oleic acid and peanut oil high in oleic
acid reverse the inhibitory effect of insulin production of the
inflammatory cytokine TNF-alpha both in vitro and in vivo
systems. Lipids Health Dis., 2009, 8, 25.
[113] Martinez-Gonzalez, M.A.; Sanchez-Villegas, A. The emerging role
of Mediterranean diets in cardiovascular epidemiology:
monounsaturated fats, olive oil, red wine or the whole pattern? Eur
J Epidemiol., 2004, 19, 9-13.
[114] Menotti, A.; Keys, A.; Kromhout, D.; Nissinen, A.; Blackburn, H.;
Fidanza, F.; Giampaoli, S.; Karvonen, M.J.; Pekkanen, J.; Punsar,
S.; et al. Twenty-five-year mortality from coronary heart disease
and its prediction in five cohorts of middle-aged men in Finland,
The Netherlands, and Italy. Prev Med., 1990, 19, 270-278.
[115] Zambon, D.; Sabate, J.; Munoz, S.; Campero, B.; Casals, E.;
Merlos, M.; Laguna, J.C.; Ros, E. Substituting walnuts for
monounsaturated fat improves the serum lipid profile of
hypercholesterolemic men and women. A randomized crossover
trial. Ann Intern Med., 2000, 132, 538-546.
[116] Bemelmans, W.J.; Broer, J.; Feskens, E.J.; Smit, A.J.; Muskiet, F.A.;
Lefrandt, J.D.; Bom, V.J.; May, J.F.; Meyboom-de Jong, B. Effect of
an increased intake of alpha-linolenic acid and group nutritional
education on cardiovascular risk factors: the Med iterranean Alpha-
linolenic Enriched Groningen Dietary Intervention (MARGARIN)
study. Am J Clin Nutr., 2002, 75, 221-227.
10 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 2 Sales-Campos et al.
[117] Fuentes, F.; Lopez-Miranda, J.; Sanchez, E.; Sanchez, F.; Paez, J.;
Paz-Rojas, E.; Marin, C .; Gomez, P.; Jimenez-Pereperez, J.;
Ordovas, J.M.; Perez-Jimenez, F. Mediterranean and low-fat diets
improve endothelial function in hypercholesterolemic men. Ann
Intern Med., 2001, 134, 1115-1119.
[118] Chrysohoou, C.; Panagiotakos, D.B.; Pitsavos, C.; Das, U.N.;
Stefanadis, C. Adherence to the Mediterranean diet attenuates
inflammation and coagulation process in healthy adults: The
ATTICA Study. J Am Coll Cardiol., 2004, 44, 152-158.
[119] de Lorgeril, M.; Salen, P. The Mediterranean diet in secondary
prevention of coronary heart disease. Clin Invest Med., 2006, 29,
154-158.
[120] de Lorgeril, M.; Salen, P. The Mediterranean-style diet for the
prevention of cardiovascular diseases. Public Health Nutr., 2006, 9,
118-123.
[121] Visioli, F.; Bogani, P.; Grande, S.; Galli, C. Mediterranean food
and health: building human evidence. J Physiol Pharmacol., 2005,
56, 37-49.
[122] Visioli, F.; Grande, S.; Bogani, P.; Galli, C. The role of
antioxidants in the mediterranean diets: focus on cancer. Eur J
Cancer Prev., 2004, 13, 337-343.
[123] Carrillo, C.; del Mar Cavia, M.; Alonso-Torre, S.R. Oleic acid versus
linoleic and alpha-linolenic acid. different effects on Ca2+ signaling
in rat thymocytes. Cell Physiol Biochem., 2011, 27, 373-380.
[124] Psaltopoulou, T.; Naska, A.; Orfanos, P.; Trichopoulos, D.;
Mountokalakis, T.; Trichopoulou, A. Olive oil, the Mediterranean
diet, and arterial blood pressure: the Greek European Prospective
Investigation into Cancer and Nutrition (EPIC) study. Am J Clin
Nutr., 2004, 80, 1012-1018.
[125] Herrera, M.D.; Perez-Guerrero, C.; Marhuenda, E.; Ruiz-Gutierrez,
V. Effects of dietary oleic-rich oils (virgin olive and high-oleic-acid
sunflower) on vascular reactivity in Wistar-Kyoto and
spontaneously hypertensive rats. Br J Nutr., 2001, 86, 349-357.
[126] Alemany, R.; Teres, S.; Baamonde, C.; Benet, M.; Vogler, O.;
Escriba, P.V. 2-hydroxyoleic acid: a new hypotensive molecule.
Hypertension, 2004, 43, 249-254.
[127] Yang, Q.; Alemany, R.; Casas, J.; Kitajka, K.; Lanier, S.M.;
Escriba, P.V. Influence of the membrane lipid structure on signal
processing via G protein-coupled receptors. Mol Pharmacol., 2005,
68, 210-217.
[128] Funari, S.S.; Barcelo, F.; Escriba, P.V. Effects of oleic acid and its
congeners, elaidic and stearic acids, on the structural properties of
phosphatidylethanolamine membranes. J Lipid Res., 2003, 44, 567-575.
[129] Ruiz-Gutierrez, V.; Muriana, F.J.; Guerrero, A.; Cert, A.M.; Villar,
J. Plasma lipids, erythrocyte membrane lipids and blood pressure of
hypertensive women after ingestion of dietary oleic acid from two
different sources. J Hypertens., 1996, 14, 1483-1490.
[130] Visioli, F.; Galli, C. Antiatherogenic components of olive oil. Curr
Atheroscler Rep., 2001, 3, 64-67.
[131] Beauchamp, G.K.; Keast, R.S.; Morel, D.; Lin, J.; Pika, J.; Han, Q.;
Lee, C.H.; Smith, A.B.; Breslin, P.A. Phytochemistry: ibuprofen-
like activity in extra-virgin olive oil. Nature, 2005, 437, 45-46.
[132] Rodriguez-Rodriguez, R.; Herrera, M.D.; de Sotomayor, M.A.;
Ruiz-Gutierrez, V. Pomace olive oil improves endothelial function
in spontaneously hypertensive rats by increasing endothelial nitric
oxide synthase expression. Am J Hypertens., 2007, 20, 728-734.
[133] Alemany, R.; Vogler, O.; Teres, S.; Egea, C.; Baamonde, C.;
Barcelo, F.; Delgado, C.; Jakobs, K.H.; Escriba, P.V.
Antihypertensive action of 2-hydroxyoleic acid in SHRs via
modulation of the protein kinase A pathway and Rho kinase. J
Lipid Res., 2006, 47, 1762-1770.
[134] Clark, C.J.; Milligan, G.; McLellan, A.R.; Connell, J.M. Guanine
nucleotide regulatory protein levels and function in spontaneously
hypertensive rat vascular smooth-muscle cells. Biochim Biophys
Acta, 1992, 1136, 290-296.
[135] Marcil, J.; de Champlain, J.; Anand-Srivastava, M.B. Overexpression
of G i-pro teins precedes the developme nt of DOCA-salt-induced
hypertension: relationship with adenylyl cyclase. Cardiovasc Res.,
1998, 39, 492 -505.
[136] Feldman, R.D.; Chorazyczewski, J. G-protein function is reduced
in hypertension. Hypertension, 1997, 29, 422-427.
[137] Escriba, P.V.; Sanchez-Dominguez, J.M.; Alemany, R.; Perona,
J.S.; Ruiz-Gutierrez, V. Alteration of lipids, G proteins, and PKC in
cell membranes of elderly hypertensives. Hypertension, 2003, 41,
176-182.
[138] Alemany, R.; Perona, J.S.; Sanchez-Dominguez, J.M.; Montero, E.;
Canizares, J.; Bressani, R.; Escriba, P.V.; Ruiz-Gutierrez, V. G
protein-coupled receptor systems and their lipid environment in
health disorders during aging. Biochim Biophys Acta, 2007, 1768,
964-975.
[139] Rodriguez Cristobal, J.J.; Benavides Marquez, F.; Villaverde
Grote, C.; Pena Sendra, E.; Flor Serra, F.; Trave Mercade, P.
[Randomised clinical trial of an intensive intervention into life-
styles of patients with hyperfibrinogenaemia in primary prevention
of cardiovascular pathology in primary health care]. Aten Primaria,
2005, 35, 260-264.
[140] Forsyth, C.B.; Solovjov, D.A.; Ugarova, T.P.; Plow, E.F. Integrin
alpha(M)beta(2)-mediated cell migration to fibrinogen and its
recognition peptides. J Exp Med., 2001, 193, 1123-1133.
[141] Danesh, J.; Collins, R.; Appleby, P.; Peto, R. Association of
fibrinogen, C-reactive protein, albumin, or leukocyte count with
coronary heart disease: meta-analyses of prospective studies.
JAMA, 1998, 279, 1477-1482.
[142] Oosthuizen, W.; Vorster, H.H.; Jerling, J.C.; Barnard, H.C.; Smuts,
C.M.; Silvis, N.; Kruger, A .; Venter, C.S. Both fish oil and olive oil
lowered plasma fibrinogen in women with high baseline fibrinogen
levels. Thromb Haemost., 1994, 72, 557-562.
[143] Dehmer, G.J.; Popma, J.J.; van den Berg, E.K.; Eichhorn, E.J.;
Prewitt, J.B.; Campbell, W.B.; Jennings, L.; Willerson, J.T.;
Schmitz, J.M. Reduction in the rate of early restenosis after
coronary angioplasty by a diet supplemented with n-3 fatty acids. N
Engl J Med., 1988, 319, 733-740.
[144] Simons, K.; Ikonen, E. Functional rafts in cell membranes. Nature,
1997, 387, 569-572.
[145] Munro, S. Lipid rafts: elusive or illusive? Cell, 2003, 115, 377-388.
[146] Shaikh, S.R.; Brzustowicz, M.R.; Gustafson, N.; Stillwell, W.;
Wassall, S.R. Monounsaturated PE does not phase-separate from
the lipid raft molecules sphingomyelin and cholesterol: role for
polyunsaturation? Biochemistry, 2002, 41, 10593-10602.
[147] Ehehalt, R.; Sparla, R.; Kulaksiz, H.; Herrmann, T.; Fullekrug, J.;
Stremmel, W. Uptake of long chain fatty acids is regulated by
dynamic interaction of FAT/CD36 with cholesterol/sphingolipid
enriched microdomains (lipid rafts). BMC Cell Biol., 2008, 9, 45.
[148] Hinz, B.; Renner, B.; Cheremina, O.; Besz, D.; Zolk, O.; Brune, K.
Lumiracoxib inhibits cyclo-oxygenase 2 completely at the 50 mg
dose: is liver toxicity avoidable by adequate dosing? Ann Rheum
Dis., 2009, 68, 289-291.
[149] Moreira, T.S.; de Sousa, V.P.; Pierre, M.B. A novel transdermal
delivery system for the anti-inflammatory lumiracoxib: influence of
oleic acid on in vitro percutaneous absorption and in vivo potential
cutaneous irritation. AAPS PharmSciTech., 2010, 11, 621-629.
[150] El Maghraby, G.M.; Campbell, M.; Finnin, B.C. Mechanisms of
action of novel skin penetration enhancers: phospholipid versus
skin lipid liposomes. Int J Pharm., 2005, 305, 90-104.
[151] Singh, S.K.; Durrani, M.J.; Reddy, I.K.; Khan, M.A. Effect of
permeation enhancers on the release of ketoprofen through
transdermal drug delivery systems. Pharmazie, 1996, 51, 741-744.
[152] Santoyo, S.; Ygartua, P. Effect of skin pretreatment with fatty acids
on percutaneous absorption and skin retention of piroxicam after its
topical application. Eur J Pharm Biopharm., 2000, 50, 245-250.
[153] Larrucea, E.; Arellano, A.; Santoyo, S.; Ygartua, P. Combined
effect of oleic acid and propylene glycol on the percutaneous
penetration of tenoxicam and its retention in the skin. Eur J Pharm
Biopharm., 2001, 52, 113-119.
[154] Gwak, H.S.; Chun, I.K. Effect of vehicles and penetration
enhancers on the in vitro percutaneous absorption of tenoxicam
through hairless mouse skin. Int J Pharm., 2002, 236, 57-64.
[155] Kim, M.J.; Doh, H.J.; Choi, M.K.; Chung, S.J.; Shim, C.K.; Kim, D.D.;
Kim, J.S.; Yong, C.S.; Choi, H.G. Skin permeation enhancement of
diclofenac by fatty acids. Drug Deliv., 2008, 15, 373-379.
Received: July 14, 2012 Revised: November 21, 2012 Accepted: November 26, 2012
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... The cluster analysis revealed six principal groups of the 18 populations of C. oleifera with a Euclidean distance of five as the threshold ( Figure 5). Population 16,17,11,12,14,15,10,2,3,4,7, and 8 were clustered into the first group, population 9 in the second, population 5 and 6 in the third, population 1 in the fourth, population 13 in the fifth, and population 18 in the sixth. ...
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Animal studies suggest that olive oil is capable of modulating functions of cells of the immune system in a manner similar to, albeit weaker than, fish oils. There is some evidence that the effects of olive oil on immune function in animal studies are due to oleic acid rather than to trace elements or antioxidants. Importantly, several studies have demonstrated effects of oleic acid-containing diets on in vivo immune responses. In contrast, consumption of a monounsaturated fatty acid (MUFA)-rich diet by humans does not appear to bring about a general suppression of immune cell functions. The effects of this diet in humans are limited to decreasing aspects of adhesion of peripheral blood mononuclear cells, although there are trends towards decreases in natural killer cell activity and proliferation. The lack of a clear effect of MUFA in humans may be attributable to the higher level of monounsaturated fat used in the animal studies, although it is ultimately of importance to examine the effects of intakes which are in no way extreme. The effects of MUFA on adhesion molecules are potentially important, since these molecules appear to have a role in the pathology of a number of diseases involving the immune system. This area clearly deserves further exploration
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