ArticlePDF AvailableLiterature Review


Background Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They are synthesized endogenously in humans, though not fully compensating all body requirements. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and have several health benefits, including anti-inflammatory and anti-cancer characters. The main body of the abstract This review capitalizes on the major omega-9 pharmacological activities in context of inflammation management for its different natural forms in different dietary sources. The observed anti-inflammatory effects reported for oleic acid (OA), mead acid, and erucic acid were directed to attenuate inflammation in several physiological and pathological conditions such as wound healing and eye inflammation by altering the production of inflammatory mediators, modulating neutrophils infiltration, and altering VEGF effector pathway. OA action mechanisms as anti-tumor agent in different cancer types are compiled for the first time based on its anti- and pro-carcinogenic actions. Conclusion We conclude that several pathways are likely to explain the anti-proliferative activity of OA including suppression of migration and proliferation of breast cancer cells, as well stimulation of tumor suppressor genes. Such action mechanisms warrant for further supportive clinical and epidemiological studies to confirm the beneficial outcomes of omega-9 consumption especially over long-term intervention.
Faragand Gad
Journal of Genetic Engineering and Biotechnology (2022) 20:48
Omega-9 fatty acids: potential roles
ininammation andcancer management
Mohamed A. Farag1* and Mohamed Z. Gad2
Background: Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found in plant
and animal sources. They are synthesized endogenously in humans, though not fully compensating all body require-
ments. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to
saturated animal fats and have several health benefits, including anti-inflammatory and anti-cancer characters.
The main body of the abstract: This review capitalizes on the major omega-9 pharmacological activities in context
of inflammation management for its different natural forms in different dietary sources. The observed anti-inflamma-
tory effects reported for oleic acid (OA), mead acid, and erucic acid were directed to attenuate inflammation in several
physiological and pathological conditions such as wound healing and eye inflammation by altering the production of
inflammatory mediators, modulating neutrophils infiltration, and altering VEGF effector pathway. OA action mecha-
nisms as anti-tumor agent in different cancer types are compiled for the first time based on its anti- and pro-carcino-
genic actions.
Conclusion: We conclude that several pathways are likely to explain the anti-proliferative activity of OA including
suppression of migration and proliferation of breast cancer cells, as well stimulation of tumor suppressor genes. Such
action mechanisms warrant for further supportive clinical and epidemiological studies to confirm the beneficial out-
comes of omega-9 consumption especially over long-term intervention.
Keywords: MUFA, PUFA, Omega-9, Inflammation; anti-cancer; oleic acid
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Omega-3, -6, and -9 fatty acids (FAs) are unsaturated
fatty acids which impose several biological effects and
health benefits. e three omega FAs are generally pre-
sent in several vegetable oils and in pharmaceutical
formulations [1]. Omega-3 and omega-6 FAs are well
characterized regarding their benefits to human health
[2]. However, omega-9 FAs have recently received wide
attention due to emerging studies and discoveries regard-
ing their biological benefits and or risks.
Omega-9 FAs (ω9 FAs or n9 FAs) are group of
unsaturated FAs that have a double bond in the 9th
position from the methyl end. ey are either mono-
unsaturated or polyunsaturated. Unlike the 3s and 6s,
Omega-9 FAs, they are considered “non-essential” FAs
e most common omega-9 FAs are hypogeic acid
(16:1 (n-9), (Z)-hexadec-7-enoic acid), oleic acid (18:1
(n-9), (Z)-octadec-9-enoic acid), elaidic acid (18:1 (n-9),
(E,)-octadec-9-enoic acid), gondoic acid (20:1 (n-9), (Z)-
eicos-11-enoic acid), mead acid (20:3 (n-9), (5Z,8Z,11Z)-
eicosa-5,8,11-trienoic acid), erucic acid (22:1 (n9),
(Z)-docos-13-enoic acid), nervonic acid (24:1 (n9), (Z)-
tetracos-15-enoic acid) (Fig. 1) [3]. Oleic acid received
the most attention in research (23,588 citations in Pub-
Med) as compared to hypogeic acid (5 results in Pub-
Med), elaidic acid (516 results in PubMed), gondoic acid
(34 results in PubMed), mead acid (145 results in Pub-
Med), erucic acid (699 results in PubMed), and nervonic
Open Access
Journal of Genetic Engineering
and Biotechnology
1 Pharmacognosy Department, College of Pharmacy, Cairo University,
Kasr El Aini St., P.B, Cairo 11562, Egypt
Full list of author information is available at the end of the article
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Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
acid (204 results in PubMed) as searched in April 2021.
Oleic acid is the most abundant in many vegetable oils
as compared to other omega-9 fatty acids. It represents
40.7% of sesame oil, 17.5% of flaxseed oil, 74.8% of olive
oil, 58.8% of rapeseed oil, and 32.7% of pumpkin seed oil.
In general, foods rich in omega-9 FAs include safflower,
sunflower, macadamia nut, hazelnut, olive oil, soybean
oil, almond butter, avocado oil, and canola oil [4]. Differ-
ent omega-9 FAs possess diverse pharmacological actions
including modulating inflammatory, lipid, cardiovascular
(CV) and cancer disorders. is review presents most
updated literature on two of the major effects of omega-9
including anti-inflammatory and anti-cancer effects.
Main text
Anti‑inammatory andanti‑cancer actions ofomega‑9
fatty acids
Oleic acid (OA)
In healthy people, OA is the most abundant FA, found in
adipocytes, cell membranes, and plasma [5]. Various ani-
mal and plant sources including olive oil, cod oil, corn oil,
and palm oil are rich in OA. It has drawn much attention
recently due to the widespread use of the Mediterranean
food that is wealthy in olive oil, one of the best source of
OA among dietary sources [6]. Also, OA is present endog-
enously as a component of hormones production and
cellular membranes [7]. OA is considered a healthier alter-
native to saturated animal fats and to possess several ther-
apeutic effects. Additionally, OA is used in pharmaceutical
industry as a solubilizing agent or emulsifier [8, 9].
Anti‑inammatory actions
OA-rich diet has positive outcomes in inflammatory-
related disorders. It modulates immune system by
activation of various immune competent cell pathways
[10]. However, controversial data exist in literature
regarding its biological value in different cellular func-
tions. Here are some positive studies that show the anti-
inflammatory actions of OA in several organs systems.
Eye inammation
OA possesses an anti-inflammatory effect against hyper-
lipidemia-induced retinal inflammation in male Wistar
rats. High OA diet (17.5% olive oil rich diet) adminis-
tered for 90 days lowered the levels of the proinflamma-
tory serum and retinal cytokines like IL-1-β, TNF-α and
MCP-1. It also decreased the expression of serum C reac-
tive protein (CRP), serum pro-inflammatory eicosanoids
(LTC4, LTB4, and PGE2), and retinal expression of BLT-1,
EP-4, EP-1, and COX-2 compared to control rats fed with
7.0% lard rich diet [10, 11]. It has been demonstrated that
OA have possible therapeutic benefits in enhancing both
hydrophilic and lipophilic compound ocular drug deliv-
ery [12]. Moreover, several studies have indicated that
lipid-based lubricants can help relieve some symptoms
of dry eye [13]. us, we believe, due to its inflammatory
actions, enhancing drug delivery and improving dry eye
effects, OA addition to topical ophthalmic preparations is
worth to be extensively studied in certain eye disorders.
Skin inammation
OA was shown to alleviate skin inflammation by altering
neutrophils’ role in immunity; however, binding to albu-
min diminishes its anti-inflammatory activity. A study
investigated the effect of incorporation of OA within
nano-structured lipid carriers (OA-NLC) in improv-
ing the anti-inflammatory actions. Results showed that
in the presence of albumin, the OA-NLC, in contrast
Fig. 1 Common omega-9 fatty acids and their natural sources in plant and animals
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Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
to unconjugated free OA, aborted elastase release and
superoxide generation, and suggestive for the improved
nano-formulation impact on OA anti-inflammatory
effect that has yet to be reported for other functions.
Topical application of OA-NLC as an ointment alleviated
neutrophil infiltration and relieved skin inflammation
severity [7, 14]. Whether such disease improvement is
correlated with increased OA levels inside the skin tissue
should be determined to be more conclusive.
Additionally, OA plays a crucial role in wound heal-
ing by inducing rapid wound closure which is essential
to prevent superimposing infections and delayed heal-
ing. Cutaneous application of OA on wounds in Wistar
rats resulted in accelerated proliferative stage, regen-
eration of epithelial cells, and proper collagen and
keratin formation. In addition, neovascularization was
enhanced in the initial inflammatory phase because
of an increase in vascular endothelial growth factor
(VEGF) expression, which exhibits an essential func-
tion in the angiogenesis process [15]. Another report
by Rodrigues etal. indicated that OA enhances NF-κB
and TNF-α secretion after 1 h of wound formation in
rats. However, a decrease in IL-6, IL-1, and MIP-3α
levels, and NF-κB release, was observed 24 h after
wounding suggesting that OA hastens wound healing’s
inflammatory processes [14].
Further studies on the anti-inflammatory action of OA
in skin included a study by [16]. e study determined
the potential of OA to act as an alternative to corticoster-
oids for the treatment of UV-induced skin inflammation.
OA was added to semisolid preparations based on Lan-
ette® or Pemulen® TR2. Both formulations reduced ear
edema in mice after repeated treatments at 24, 48, and
72 h after UVB exposure. e anti-inflammatory prop-
erty appeared to be mediated by glucocorticoid recep-
tors. e authors suggested the use of OA as a promising
alternative to glucocorticoids given that OA is safe and
not photosensitive even at relatively high dose (13%) [16].
Figure2 summarizes the postulated effects of OA on skin
Lung inammation
Pneumonitis is a general term that refers to lung tissue
inflammation. Physicians commonly use the term pneu-
monitis to refer to noninfectious causes of lung inflam-
mation. Lung inflammation may be acute or chronic,
and there are a variety of causes, including environmen-
tal factors, infections, and diseases such as asthma and
bronchitis [17]. Lung damage caused by OA is a common
used model that closely resembles human disease [18].
However, OA has been found to possess anti-inflamma-
tory activities towards activated neutrophils. OA-based
Fig. 2 Summary of the action mechanisms of oleic acid (OA) in modulating skin inflammation and wound healing effects
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Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
nanosystems mitigated against acute respiratory distress
syndrome in mice via the suppression of neutrophils [19].
Liver inammation
When a disease-causing microbe or drug attacks liver
cells, liver inflammation occurs. e term hepatitis refers
to liver inflammation. Hepatitis is mainly caused by a
viral infection, but it may also be caused by an autoim-
mune disorder. Alcohol, toxins, and some medications
can also cause liver damage, which can lead to inflam-
mation. Hepatitis may also be caused by hereditary dis-
orders, as well as a chronic obstruction of bile flow. e
type of hepatitis determines the severity, treatment,
and outcome of the liver inflammation. Fibrosis, cirrho-
sis, and hepatocellular carcinoma may all be caused by
chronic liver inflammation [20].
Extra virgin olive oil, rich in OA, can help prevent
inflammation, mitochondrial dysfunction, insulin resist-
ance, endoplasmic reticulum (ER) stress, and oxidative
stress by activating various signaling pathways in hepatic
parenchymal cells. e following are the most impor-
tant pathways that lead to the resolution or prevention of
liver injury: (1) induction of the nuclear factor erythroid
2-related factor 2 (Nfr2), leading to antioxidant signals;
(2) suppression of (NF-κB), which prevents the cellular
inflammation response; and (3) suppression of the PERK
signaling pathway that results in prevention of autophagy,
ER stress, and lipogenic response [21]. OA also reduces
hepatocellular lipotoxicity caused by palmitic acid by
inhibiting pyroptosis and ER stress [22].
Sepsis is a potentially fatal disease, which occurs when
the body’s immune system starts to attack its own tis-
sues in response to an infection. Septic shock may
develop from sepsis. This dangerously low blood pres-
sure can lead to organ failure and death. While any
infection—viral, bacterial, or fungal—may cause sep-
sis, infections of the lungs, urinary tract and digestive
systems, blood (bacteremia), and skin (catheter sites,
burns or wounds) are the most common causes [23].
In a study by Medeiros-de-Moraes etal., mice devel-
oped sepsis using cecal ligation and puncture (CLP)
model and upon treatment for 14 days with omega-9
elevated levels of the anti-inflammatory IL-10 con-
current with reduction of proinflammatory IL-1β and
TNF-α levels in fluid of septic animals. Furthermore,
omega-9 intake reduced systemic levels of corticos-
terone. According to the authors, omega-9 can play a
positive anti-inflammatory role in sepsis by reducing
leukocyte influx and rolling, neutralizing cytokine out-
put, and regulating bacterial growth through a PPAR-γ
signaling pathway [24].
In another study, OA pretreatment for 14 days
improved longevity, prevented kidney and liver damage,
and reduced plasma levels of NEFA in mice exposed to
CLP sepsis model. OA intake also decreased reactive oxy-
gen species (ROS) and increased 5’ AMP-activated pro-
tein kinase (AMPK), carnitine palmitoyltransferase IA
(CPT1A), and uncoupling protein 2 (UCP2) levels [25].
Ulcerative colitis andintestinal inammation
Ulcerative colitis (UC) is an inflammatory bowel disor-
der that causes ulcers and inflammation in the gastroin-
testinal tract. UC occurs when the colon or/and rectum
lining becomes inflamed. Genetic predisposition, dys-
regulated immune responses, defects in epithelial bar-
rier, and environmental factors all contribute in the
pathogenesis of that disease. Despite the fact that there
is no cure, medication can significantly reduce signs
and symptoms of the disease and can lead to long-term
remission [26].
In a trial to reduce the burden of meat products diet
in cases of ulcerative colitis, Fernández etal. fed experi-
mentally induced UC rats with acorn-fed ham rich in
OA. e gut microbiota was altered because of the
diet, with significant increase in bacterial genera hav-
ing anti-inflammatory properties (Alistipes, Blautia,
Dorea, Parabacteroides). It also had a powerful anti-
inflammatory effect, which helped to avoid UC symp-
toms including macroscopic score of colitis, disease
activity index, density of inflammatory cell in colon,
epithelium alteration in colon mucosa, proinflamma-
tory IFN-γ and IL-17 levels, and myeloperoxidase titers
in colon as compared to rats fed conventional vegeta-
ble diet [27]. In another report, Cariello etal. examined
whether extra-virgin olive oil (EVO) intake is able to
exert a prophylactic role in a dextran sodium sulfate
(DSS) colitis-mediated animal model. Results revealed
that EVO administration reduced the rectal bleeding,
loss in body weight, and TGFβ, IL-1β, and IL-6 levels.
It also reduced intestinal permeability and inflamma-
tion-related histopathological features [28]. A summary
of OA anti-inflammatory actions in different organs is
depicted in Fig.3.
Insulin resistance (IR) andtype 2 diabetes mellitus (T2DM)
Among the main factors involved in the development
and activation of IR and T2DM is mitochondrial dys-
function that may lead to inefficient fatty acid oxida-
tion (FAO). OA enhanced FAO genes expression by
PGC1α deacetylation through PKA-dependent stimula-
tions of SIRT1-PGC1α complex. e anti-inflammatory
actions of OA also included lowering the expression of
the inflammatory mediators; E-selectin and sICAM,
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Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
upregulating free fatty acid receptor-4 (FFAR4), pro-
moting M2 expression, decreasing phosphate and
tensin homolog (PTEN), increasing adiponectin, and
downregulating protein phosphatase 2A (PP2A). OA
also controlled IR and T2DM by improving β cell func-
tion and endothelial functions, oxidative stress, hypo-
thalamic function, glucolipotoxicity, apoptosis, and
dysregulation of enzymes [29]. Whether administration
of OA with anti-diabetic agents like metformin could
lead to a synergized action has yet to be determined.
Anti‑cancer actions
OA has been shown in numerous reports to inhibit cellu-
lar proliferation in several tumor cell lines. OA inhibited
HER2 overexpression, a well-known oncogene involved
in the development, and metastasis of numerous human
cancers. In carcinoma cells, OA also plays a signifi-
cant role in the intracellular calcium signaling pathways
related to apoptosis and growth induction. e mecha-
nisms underlying the apoptotic event caused by OA are
linked to the rise in intracellular caspase 3 activity and
the development of ROS [30].
OA downregulated cancer activity of human esopha-
geal cells (HEC) through several mechanisms includ-
ing suppressing cell proliferation, and cellular migration
and adhesive properties as mediated via activating tumor
suppressor genes (p27, p21 and p53). Although OA
treatment of HEC did not influence the number of colo-
nies, it inhibited the colony size remarkably. Further, OA
is recognized for its anti-proliferative effect in other types
of cancer including colorectal cancer, where OA induced
apoptosis as well as breast cancer by regulating HER2
gene expression [6]. Nevertheless, more studies using
in vivo animal grafted models should be performed to
confirm OA anti-tumor actions.
Jiang et al. explored OA anti-cancer properties and
mechanisms in tongue squamous cell carcinoma (TSCC).
Results revealed that OA efficiently suppressed prolif-
eration of TSCC cells. It markedly promoted cell cycle
G0/G1 arrest, decreased Bcl-2 and Cyclin D1 expres-
sion, and elevated the proportion of apoptotic cells, con-
current with increased p53 expression and caspase-3
cleavage. OA also caused autolysosome formation and
decreased p62 expression as well as LC3 I/LC3 II ratio.
Furthermore, post-OA therapy, expression of p-mTOR,
p-Akt, p-4E-BP1, p-S6K, and p-ERK1/2, was dramati-
cally reduced in TSCC cells. It was concluded from the
study that OA possessed an anti-cancer activity in TSCC
through enhancing autophagy and apoptosis via inhibit-
ing the Akt/mTOR signaling pathway [31].
Proteins such as α-lactalbumin and lactoferrins are
among the other macromolecules with which OA inter-
acts and mediates its anti-cancer properties. In patients
with advanced cancer, a combination of OA and Gc
Fig. 3 Oleic acid (OA) anti-inflammatory action mechanisms in the different body organs viz. eye, skin, lung, liver, blood vessels, and intestine
Page 6 of 11
Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
protein-derived macrophage activating factor (GcMAF)
was shown to have significant influence on immune sys-
tem activation and decrease of tumor mass [32]. e
release of nitric oxide is linked to the GcMAF stimulat-
ing effects on macrophages. Furthermore, OA increased
the efficacy of cancer drugs in a synergistic manner.
For instance, OA increased the potency of Herceptin, a
breast cancer drug that targets the HER-2/neu gene [33].
In addition, n-butyl and phenyl derivatives of OA exhib-
ited great growth inhibitory activity in human HT-29
colon and MCF-7 breast cell lines [34]. Synthesis of other
OA analogues could help identify even more active anti-
tumor agents based on OA using either in silico drug
modelling or combinatorial chemistry.
A summary of OA anti-cancer effects and action mech-
anisms in different cancer types is depicted in Fig.4.
Elaidic acid (EA)
Elaidic acid, trans-isomer of oleic acid, has received
recently wide consideration being a common trans-fat,
which has been linked to heart disease. EA occurs natu-
rally in bovine and caprine milk (around 0.1% of the FAs)
[35], some meats, in addition to plant sources such as
durian fruits.
Studies in human have found a connection between the
usage of industrial trans-fatty acids (TFAs), such as EA,
and the incidence of cardiovascular diseases, prompting
many countries to pass legislation prohibiting the use of
industrial TFAs in food. However, TFA cannot be totally
removed from human food because they are naturally
found in dairy and meat derived from ruminant animals
Da Silva etal. assessed the anti-inflammatory proper-
ties of several TFAs, including EA in several cell lines
including (HUVEC) and (HepG2) cells for 24 h at con-
centrations ranging from 5-150 μM. Stearoyl-CoA
desaturase (SCD-1), a main enzyme in FAs biosynthesis,
expression increased after EA was added. EA additionally
decreased expression of inflammatory genes in HUVEC
cells, but not HepG2 cells [36], suggestive for a selective
effect against cancer cell lines.
In general, administration of TFA, including EA, rep-
resents health hazards in many studies. Wang et al.
reported that higher circulating EA is connected with
increased long-term morbidity and mortality in the gen-
eral population [17]. Li etal. presented same conclusion,
reporting that plasma EA levels are linked to an elevated
risk of CVD mortality [37].
EA also induced cholesterogenesis in Hepa1-6
hepatoma cells invitro by activating the sterol regula-
tory element-binding protein (SREBP) cleavage-activat-
ing protein (SCAP), mostly by reducing intracellular free
cholesterol and cholesterol-dependent SCAP repression.
e increase in liver cholesterol and non-alcoholic fatty
liver disease (NAFLD) caused by industrial TFA may be
attributed to this pathway. In contrast to cis-unsaturated
Fig. 4 Summary of oleic acid (OA) action mechanisms as anti-tumor agent in different cancer types
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Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
and saturated diets, EA increased liver/gonadal fat mass
ratio, hepatic cholesterol content, alanine aminotrans-
ferase activity, steatosis, and markers of fibrosis in mice,
implying increased NAFLD [38]. is provided further
evidence that industrial TFA can cause liver damage, pri-
marily by initiating fatty liver that develop into fibrosis.
In contrast to cis-unsaturated fatty acids, the cancer-
promoting properties of TFAs have been well docu-
mented. Kishi etal. investigated EA’s effects and signaling
in cells of colorectal cancer (CRC). Oral consumption
of EA to mice increased the metastasis of HT29 human
CRC cells, which were inserted into the mice scapu-
lar subcutaneous tissue. EA was incorporated into the
plasma membrane’s cholesterol rafts that embraced epi-
dermal growth factor receptors (EGFR). In HT29 cells,
EA elevated nanog and c-myc levels, while decreasing
PGC-1A levels via lipid raft-linked EGFR signaling [39].
Ohmori etal. also demonstrated the enhancement of sur-
vival, growth, and invasion of the colorectal cancer cell
lines, HT29, and CT26 by EA [40].
Other negative effect of EA included its neurotoxic-
ity. Following treatment of SH-SY5Y neuroblastoma
cells with various levels of EA (10, 20, 50, 100, 200,
400, and 800 μM) for 24 h at 37 oC, suppression of cell
viability, elevation of cell apoptosis, and loss of mito-
chondrial membrane potential (MMP) were observed.
Furthermore, EA caused significant changes in cellular
redox status. Higher doses of EA (200, 400, or 800 μM)
increased the production of ROS, including lipid perox-
ide and malondialdehyde levels, upregulated Nrf-2, and
downregulated heme oxygenase 1 (HO-1), two primary
anti-oxidative players. ese results inferred that EA sup-
pressed SH SY5Y cell growth and enhanced apoptosis by
increasing oxidative stress and triggering the ER stress/
UPR signaling pathway as well as the GRP78/ATF4/
CHOP pathway [41]. Whether examined doses of elaidic
acid in these studies are comparable to its level in natural
resources should be made to be more conclusive for these
Gondoic acid (GA)
GA, cis-11-Eicosenoic acid, is found in a variety of plant
oils and nuts; in particular jojoba oil [42]. It is also found
in red cell membrane with upsurge levels in children with
regressive autism. No studies were found regarding the
health effects of this particular omega-9 fatty acid and
warranting for future work to verify its health benefits or
Mead acid (MA)
Mead acid is formed de novo in animals derived from
OA. Its elevated level in blood is indicative of “essential”
fatty acid (EFA)deficiency[43]. MAs functions in normal
physiological conditions had not been thoroughly stud-
ied. Increased metabolism of oleic acid to MA occurs
in the absence of adequate α-linolenic acid and linoleic
acid [44]. MA levels in chicken and human infant carti-
lage have long been recognized to be high, even in the
absence of EFA deficiency. It was proposed that MA pre-
vents cartilage calcification, and also to occur in avascu-
lar tissues like the cornea and lens [45].
With regard to the anti-inflammatory features of MA,
Yoshida et al. investigated the impact of MA-enriched
diet on experimentally induced bowel lesions. Rats
were given either an MA-enriched or a standard diet.
Acute bowel lesions were induced, after 7 days of feed-
ing, by injecting 10 mg/kg indomethacin subcutaneously.
Results indicated that dietary supplementation of MA
(5% M. alpine oil-enriched diet; M. alpine oil contains
17% MA) had both therapeutic and prophylactic actions
on experimentally induced bowel lesions [46]. In a dif-
ferent aspect, simultaneous addition of MA as adjunct
treatment with aggregating agents to platelets enhanced
platelets’ response [47].
Concerning the anti-cancer properties of MA,
Kinoshita etal. explored the impact of MA on the pro-
duction and proliferation of N-methyl-N-nitrosourea
(MNU)-induced mammary carcinoma in rats. All
mammary tumors were found to be luminal A carci-
noma. e MA-containing diet dramatically inhibited
the development and progression of mammary car-
cinogenesis via the suppression of cell proliferation
[48]. MA also inhibited the growth of KPL-1 human
breast carcinoma both invivo and invitro, but had no
effect on angiogenesis. VEGF signaling to tumor cells
was one of the proposed mechanisms of action [49].
Furthermore, MA inhibited some pro-cancerous prop-
erties in three different human cell lines: MCF-7 from
breast, T-24 from urothelium, and HRT-18 from colon
(Heyd and Eynard, 2003).
Erucic acid
Erucic acid is mostly abundant in Brassica seeds (Eruca
sativa), known asarugula(USA) or rocket (UK), in addi-
tion to Indian mustard (Brassica juncea) and rapeseed
(Brassica napus) [50].
Erucic acid is a PPAR-δ ligand, found to lead to
improved cognitive parameters in animal models through
its anti-oxidative and anti-inflammatory actions [51]. It
may also act as a neuroprotective, anti-tumor, and myelin
protective agent in Parkinson’s disease, glioblastoma, and
neuroblastoma [52]. Its remyelinating property might
also be valuable in the management of multiple sclerosis
[52]. e suppression of p38 MAPK and NF-B signaling
are thought to be the molecular mechanisms through
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Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
which erucic acid exerts its anti-inflammatory properties
(Liang etal. 2020) [53].
Regarding the anti-tumor effect, erucic acid is pre-
sent abundantly in the Chinese diet and suggestive that
the low brain cancer frequency in children among the
Chinese population is credited to high content of erucic
acid in Chinese women breast milk [54]. Erucic acid is
believed to possess an anti-tumor activity especially in
C6 glioblastoma, where erucic acid suppressed cellular
proliferation by blocking synthesis of DNA (arresting
the cell cycle at S-phase) as well as direct cellular inter-
action [51]. e anti-proliferative action of erucic acid
on the glioblastoma cells is related to its agonistic effect
on peroxisome proliferator-activated receptors (PPARs).
Additionally, co-administration of erucic acid with doxo-
rubicin alleviated the cardio toxic and hepatotoxic effects
of doxorubicin and with doxorubicin better tolerated
with enhanced anti-cancer effect [55]. Nevertheless,
erucic acid has been shown to induce myocardial lipi-
dosis, hepatic steatosis, and cardiac lesions in animals.
ese effects limit its inclusion in edible oils by regula-
tory agencies [56] and reduce its clinical applications.
Nervonic acid (NA)
NA is (Z)-15-tetracosenoic acid, 24:1 (n9) occurs natu-
rally as an extension product of oleic acid, with erucic
acid as the immediate precursor. NA is abundant in
peripheral nervous tissue and in the animal brains white
matter, where nervonyl sphingolipids are abundant in
nerve fiber myelin sheath [52]. NA has received much
attention owing to its close association with brain devel-
opment. NA levels of human brain sphingolipids rise dra-
matically from birth to a peak at 4 years, and to remain
constant afterwards [57]. Natural resources of NA
include oil crop seeds especially seed oils of Lunaria spe-
cies and oil-producing microalgae [58]. NA is required
for the formation of brain myelin and can be used as a
marker of brain maturity. Infants’ neurodevelopment can
be aided by formula feeding, and customers and produc-
ers may benefit from a healthier alternative to milk pow-
der. However, the contradictory findings regarding NA
contents of patients with psychosis, depressive disorders,
Alzheimer’s disease, and cardiovascular disease warrant
further study.
In a study by Lewkowicz etal. on lipids profiling in
an induced model of brain autoimmune encephalo-
myelitis, it was shown that during acute inflamma-
tion, NA biosynthesis was downregulated as a result of
shifting lipids metabolism pathways of common sub-
strates into pro-inflammatory arachidonic acid forma-
tion [59]. NA has been shown to alleviate Parkinson’s
disease-related tremors and multiple sclerosis-related
numbness. It can also be used to treat schizophrenia
and to alleviate the symptoms of Alzheimer’s disease
in the early stages [58].
Hypogeic acid (HA)
Hypogeic acid is found in human milk. Very few studies
involving HA biological effects have been found in the lit-
erature. In one study by Astudillo etal., the anti-inflam-
matory properties of hypogeic acid along with palmitoleic
acid were investigated. e majority of hexadecenoic
fatty acids were esterified in a specific pattern, palmitic
acid at sn-1 location and hexadecenoic acid at sn-2 as
revealed in mouse peritoneal macrophages. When mac-
rophages are stimulated with inflammatory stimuli, this
species decreases dramatically. Although the majority of
the released hexadecenoic acid appeared as a free FA, a
large portion is moved to other phospholipids to con-
struct hexadecenoic acid-containing inositol phospholip-
ids that are further recruited to yield fatty acid esters of
possible anti-inflammatory properties [60]. e findings
suggest that conversion of these fatty acids to other lipid
mediators can account for some of their anti-inflamma-
tory activity. HA has been proposed as a potential marker
for the development of foamy cells in atherosclerosis, but
whether such marker is a reactive homeostasis response
or indicative of disease progression should be clarified.
Omega-9 fatty acids exhibit essential myriad of pharma-
cological activities that pose them as potential candidate
to alleviate many pathological conditions. e observed
anti-inflammatory effects reported for oleic acid, mead
acid, and erucic acid were directed to attenuate inflam-
mation in several physiological and pathological condi-
tions such as wound healing and eye inflammation by
altering the production of inflammatory mediators, mod-
ulating neutrophils infiltration, and altering VEGF effec-
tor pathway.
e anti-neoplastic action of omega-9 fatty acids
is though controversial compared to its anti-inflam-
matory actions, with the effect varies with the type of
cancerous tissue and the effector pathway. Most docu-
mented anti-neoplastic action of omega-9 is evidenced
in case of olive oil-rich diets. ese diets enriched in
oleic acid content are believed to possess chemo pre-
ventive effect against breast cancer. Oleic acid anti-
tumor action is mediated via multiple mechanisms
including suppression of proliferation and migration
and breast cancer cells, as well activation of tumor sup-
pressor genes.
On the other hand, several pathways are believed to
explain the proliferative activity of OA. In MCF-7 and
MDA-MB-231 breast carcinoma lines, OA enhanced
Page 9 of 11
Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
metastasis and cellular proliferation through activation of
free fatty acid receptor 1 (FFAR1) and FFAR4 receptors
that are activated by medium-chain FAs like OA. Such
receptors are also present on the surface of other cells
such as insulin secreting in pancreatic β cells and adipose
tissue, and upon activation, they alter the intracellular
Ca2+ concentration. In addition, OA activates AKT path-
way (protein kinase B) where AKT2 induces production
of Integrin B that facilitates invasion along with AKT-1
activation that promotes cell migration as well along with
epidermal growth factor receptor (EGFR) OA-dependent
activation [61].
In general, reports on the anti-inflammatory and
anti-cancer actions of omega-9 FAs, other than oleic
acid, are quite scarce especially for the clinical studies.
Further research is warranted to provide more conclu-
sive data about their prophylactic and therapeutic value
in those two widespread disorders. Figure 5 summa-
rizes the pro- and anti-cancer actions of omega-9 FAs.
ese results pose omega-9 FAs as promising therapeu-
tic agents warranted to be further studied in different
pathological conditions, especially in inflammation and
cancer. ese effects have yet to be confirmed though
using randomized controlled trials to reveal solid con-
clusive evidence for comparative actions using isolated
oils enriched in certain omega-9 fatty acids or better
using individual fatty acids. Execution of more epide-
miological studies with more advanced methodologies
(lipidomics, metabolomics, and molecular techniques)
will yield more reliable information about omega-9
action mechanisms at different cellular levels and pro-
vide the optimum ratio of these different fatty acids to
be recommended for dietary fat intake. How gut micro-
biota interact with omega-9 to mediate for its anti-
inflammatory effects if any is also an area less explored
and should be considered using ex vivo or ideally
invivo assays. Modification of these fatty acids using
different techniques, i.e., nanoformulation, nanoemul-
sion, and encapsulation, should also help improve their
bioavailability and ultimate biological effects.
FAs: Fatty acids; ω9 FAs: Omega-9 FAs; OA: Oleic acid; IR: Insulin resist-
ance; T2DM: Type 2 diabetes mellitus; TSCC: Tongue squamous cell
carcinoma; EA: Elaidic acid; SREBP: Sterol regulatory element-binding
protein; SCAP: Cleavage-activating protein; NAFLD: Non-alcoholic fatty
liver disease; TFAs: Trans-fatty acids; SCD-1: Stearoyl-CoA desaturase; CRC
: Colorectal cancer; GA: Gondoic acid; MA: Mead acid; NA: Nervonic acid;
HA: Hypogeic acid; FFAR1: Free fatty acid receptor 1; EGFR: Epidermal
growth factor receptor.
Not applicable.
Authors’ contributions
MF conceived the concept. MG wrote the manuscript. MF and MG cor-
rected and shaped the manuscript. All authors read and approved the final
Not applicable.
Availability of data and materials
Not applicable.
Fig. 5 Anti- or pro-cancer actions of omega-9 fatty acids
Page 10 of 11
Faragand Gad Journal of Genetic Engineering and Biotechnology (2022) 20:48
Ethics approval and consent to participate
Not applicable.
Consent for publication
The authors agree on publishing rules of this journal.
Competing interests
The authors declare that they have no competing interests.
Author details
1 Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr El
Aini St., P.B, Cairo 11562, Egypt. 2 Department of Biochemistry, Faculty of Phar-
macy & Biotechnology, The German University in Cairo, Cairo, Egypt.
Received: 6 January 2022 Accepted: 9 March 2022
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... This promotes the stabilization of a closed state conformation [24]. By changing the production of inflammatory mediators, modulating neutrophil infiltration and changing the VEGF effector pathway, the observed anti-inflammatory effects of oleic acid, mead acid (an omega-9 fatty acid) and erucic acid were intended to reduce inflammation in a variety of physiological and pathological conditions and be effective for wound healing and eye inflammation [25]. In a study conducted by Harima et al. [26]. ...
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HOW TO CITE THIS Momo et al. (2023) Characterizations of the active ingredients of methanol extract of weaver ant and its analgesic activity in mice. Mediterr J Pharm Pharm Sci. 3 (2): 34-44. Abstract: Pain according to WHO has been one of the greatest issues to plague man, in the bid to handle this issue of pain, man has sought to look for other means to reduce pain to its bare minimum. This study is aimed at investigating the analgesic activity of the methanolic extract of the African weaver ant using acetic acid-induced writhing, hot plate method, and formalin-induced pain models in Swiss mice. In the acetic acid test, the methanolic extract of Oecophylla longinoda (OL) was administered orally at 200 and 400 mg/kg body weight while aspirin was administered at 100 mg/kg and tween 80 served as standards. In the hot plate and formalin models, the extract was administered orally at two doses of 200 and 400 mg/kg while pentazocine at 10 mg/kg and tween 80 at 10 mg/kg served as standards. The methanolic extract of OL exhibited significant analgesic activity in all the models, with none less than the standard significant difference (p < 0.05) by increasing the reaction time of the mice after treatment in comparison to the control. The 400 mg/kg extract in the acetic acid-induced writhing response has a percentage inhibition of 52.7%, which shows how well the extract inhibits pain in mice. The methanolic extract significantly reduced pain response in mice, with a p-value of 0.03, 0.02, and 0.001 in all the test models, respectively. OL increased the pain threshold over time and significantly reduced the writhing response that mice experience from acetic acid. Furthermore, pretreatment with OL significantly and dose-dependently decreased the early and late phases of formalin-induced pain in mice. Thus, these findings suggest that the methanolic extract of OL acts on central and peripheral pain pathways.
... MUFA and PUFA: Studies have found that MUFA can mitigate inflammation by modulating the production of inflammatory mediators and regulating neutrophil infiltration [41]. Potential underlying mechanisms include the reduction of endoplasmic reticulum stress [42], enhancement of vascular endothelial inflammation, and systemic inflammatory responses [43]. ...
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Background and aims This study aimed to investigate the association between the Dietary Inflammatory Index (DII) and dyslipidemia, as well as to evaluate the mortality risk associated with DII in participants with dyslipidemia. Methods Data from the National Health and Nutrition Examination Survey database were divided into dyslipidemia and non-dyslipidemia groups. The association between DII and dyslipidemia was investigated using the weighted chi-square test, weighted t-test, and weighted logistic regression. Weighted Cox proportional hazards models were used to estimate the hazard ratios and 95% confidence intervals for all-cause and cardiovascular disease-related mortality within the dyslipidemia group. Results A total of 17,820 participants, including 4,839 without and 12,981 with dyslipidemia were analyzed in this study. The results showed that DII was higher in the dyslipidemia group compared to the non-dyslipidemia group (1.42 ± 0.03 vs. 1.23 ± 0.04, P < 0.01). However, for energy, protein, carbohydrates, total fat, saturated fat, and iron, DII was lower in participants with dyslipidemia. Logistic regression analysis revealed a strong positive association between DII and dyslipidemia. The odds ratios for dyslipidemia from Q1 to Q4 were 1.00 (reference), 1.12 (0.96–1.31), 1.23 (1.04–1.44), and 1.33 (1.11–1.59), respectively. In participants with dyslipidemia, a high DII was associated with high all-cause and cardiovascular mortality. Conclusion DII was closely associated with dyslipidemia. A pro-inflammatory diet may play a role in unfavorable consequences and is linked to both all-cause mortality and cardiovascular death in patients with dyslipidemia. Participants with dyslipidemia should pay attention to their anti-inflammatory dietary patterns.
... Available research data state that the average MUFA content in various cheeses is 179.90 mg/g of fat, and the average PUFA content is at a similar level [102,111]. Dietary n-3 polyunsaturated fatty acids are recommended for heart disease prevention, and linolenic acid exhibits anti-carcinogenic and anti-atherogenic effects [112][113][114], whereas n-6 PUFAs improve sensitivity to insulin [115]. However, taking into consideration that dairy products are rich in SFA, their enrichment with BIBs becomes very prospective. ...
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The aim of this study was to apply raspberry (Ras), blueberry (Blu) and elderberry (Eld) industry by-products (BIB) for unripened cow milk curd cheese (U-CC) enrichment. Firstly, antimicrobial properties of the BIBs were tested, and the effects of the immobilization in agar technology on BIB properties were evaluated. Further, non-immobilized (NI) and agar-immobilized (AI) BIBs were applied for U-CC enrichment, and their influence on U-CC parameters were analyzed. It was established that the tested BIBs possess desirable antimicrobial (raspberry BIB inhibited 7 out of 10 tested pathogens) and antioxidant activities (the highest total phenolic compounds (TPC) content was displayed by NI elderberry BIB 143.6 mg GAE/100 g). The addition of BIBs to U-CC increased TPC content and DPPH- (2,2-diphenyl-1-picrylhydrazyl)-radical scavenging activity of the U-CC (the highest TPC content was found in C-RaNI 184.5 mg/100 g, and strong positive correlation between TPC and DPPH- of the U-CC was found, r = 0.658). The predominant fatty acid group in U-CC was saturated fatty acids (SFA); however, the lowest content of SFA was unfolded in C-EldAI samples (in comparison with C, on average, by 1.6 times lower). The highest biogenic amine content was attained in C-EldAI (104.1 mg/kg). In total, 43 volatile compounds (VC) were identified in U-CC, and, in all cases, a broader spectrum of VCs was observed in U-CC enriched with BIBs. After 10 days of storage, the highest enterobacteria number was in C-BluNI (1.88 log10 CFU/g). All U-CC showed similar overall acceptability (on average, 8.34 points); however, the highest intensity of the emotion “happy” was expressed by testing C-EldNI. Finally, the BIBs are prospective ingredients for U-CC enrichment in a sustainable manner and improved nutritional traits.
... Anti-kanser ve anti-infilamatuar özellik gösteren n-9 yağ asitleri ise kontrolsüz hücre poliferasyonunu inhibe etmektedir ve tümör bakılayıcı genlerin aktivasyonuna katılmaktadır. Buna ek olarak, reaktif oksijen türlerinin oluşumunu da azaltmakta ve anti-oksidan etki göstermektedir (Farag & Gad, 2022). ...
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Değerli okuyucularımız; Sağlık bilimleri alanında özveri ile çalışan akademisyenlerimizin büyük emekleri ile hazırladığımız kitabımız, geniş kapsamlı bir yaklaşım ile bizlere güncel bilgiler sunmaktadır. Tıpta temel bilimler ile klinik bilimler birlikte çalışarak sürekli önemli gelişmeler kaydetmektedir. Konular üzerinde araştırma yaparken ona birçok bakış açısı ile bakarak yaklaşmamız, ayrıntıları fark etmemize, yeni fikirler ve çözümler üretmemize katkı sağlamaktadır. Kitabın zengin içeriği ve perspektifi ile yazarlarımızın bilim dünyasına katkı sunan yorumlarının, bilime gönül veren insanlar için yararlı olacağını umut etmekteyim. Hastalıkların önlenmesi, erken tanısı ve etkin tedavisi için bilimsel alanlarda sabırla çalışan yol arkadaşlarımın çalışmalarına yeni ufuklar açmasını dilerim. Kitabımıza destek veren yazar kadromuz ve her seferinde aynı heyecan ile hazırladığımız yeni eserlerde büyük çabalarından dolayı yayın ekibimize teşekkür ederim. Prof. Dr. Hülya Çiçek
... It is important to highlight that the literature is not conclusive about the protective or deleterious activities of PUFAs and MUFAs, except for the beneficial effect of ω-3 and the harmful actions of SFA high consumption (Butler et al., 2020;Christensen et al., 2019;DiNicolantonio and O'Keefe, 2017;Djuricic and Calder, 2021;Farag and Gad, 2022). ...
The ostrich oil (OO) has been topically used for decades to treat skin diseases. Its oral use has been encouraged through e-commerce advertising several health benefits to OO without scientific evidence on its safety or effectiveness. This study presents the chromatographic profile of a commercially available OO and its acute and 28-day repeated dose in vivo toxicological profiles. OO anti-inflammatory and antinociceptive effects were also investigated. Omega-9 (ω-9; oleic acid; 34.6%) and -6 (linoleic acid; 14.9%) were detected as OO main constituents. A high single dose of the OO (2 g/kg of ω-9) demonstrated no or low acute toxicity. However, when orally treated with OO (30-300 mg/kg of ω-9) for 28 consecutive days, mice exhibited altered locomotor and exploratory activities, hepatic damage, and increased hindpaw sensitivity accompanied by increased levels of cytokine and brain-derived neurotrophic factor in their spinal cords and brains. Lack of anti-inflammatory or antinociceptive activities was also evidenced in 15-day-OO treated mice. These results indicate that chronic consumption of OO induces hepatic injury, in addition to neuroinflammation and subsequent hypersensitivity and behavioural changes. Thus, there is no evidence to support OO use to treating illness in humans.
Erucic acid is a single unsaturated fatty acid that falls under the omega‐9 fatty acid family. It was suggested to treat Wistar rats with lipopolysaccharide (LPS)‐induced memory impairment and minimize cognitive impairment. A total of 30 animals were randomized: group I was normally treated group, group II was administered with LPS, group III was treated with LPS along with erucic acid at the dose of 10 mg kg –1 p.o. –1 , group IV was treated with LPS along with erucic acid at 20 mg kg –1 p.o. –1 and group V was the erucic acid per se group provided at the dose of 20 mg kg –1 p.o. –1 per se. Behavioral tests were evaluated by using the Morris water maze and Y‐maze. Biochemical analysis including acetylcholine esterase (AChE), choline acetyltransferase (ChAT), glutathione (GSH), catalase activity (CAT), superoxide dismutase (SOD), and nitric oxide (NO) along with proinflammatory mediators tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), caspase 3, and neuroinflammatory biomarker (nuclear factor kappa B‐NF‐κB) were measured. Erucic acid produced substantial behavioral improvement in the Y‐maze test, including spontaneous alterations and reduced latency time during acquisition, and a longer duration of time in the consolidation phase undergoing the MWM test. Furthermore, erucic acid improved the AChE, proinflammatory markers, and oxidative stress as well as restoring endogenous antioxidant levels, ChAT, caspase 3, and NF‐κB levels. Erucic acid may be a therapeutic component for conditions related to memory disorders such as memory impairment, enhances memory functioning, and protects against neuronal damage.
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Monounsaturated fatty acids (MUFAs) have been the subject of extensive research in the field of cancer due to their potential role in its prevention and treatment. MUFAs can be consumed through the diet or endogenously biosynthesized. Stearoyl-CoA desaturases (SCDs) are key enzymes involved in the endogenous synthesis of MUFAs, and their expression and activity have been found to be increased in various types of cancer. In addition, diets rich in MUFAs have been associated with cancer risk in epidemiological studies for certain types of carcinomas. This review provides an overview of the state-of-the-art literature on the associations between MUFA metabolism and cancer development and progression from human, animal, and cellular studies. We discuss the impact of MUFAs on cancer development, including their effects on cancer cell growth, migration, survival, and cell signaling pathways, to provide new insights on the role of MUFAs in cancer biology.
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The present work is focused on the physicochemical characteristics, chemical composition, and some biological activities of Koelreuteria paniculata seed oil. The glyceride oil, obtained with a Soxhlet apparatus by extraction with hexane, was characterized by a relatively high oil content (over 20%), and it is defined as a non-drying oil (iodine value—44 gI2/100 g) with good oxidative stability (over 50 h). There were identified 11 fatty acids, 6 sterols, 3 tocopherols, and 6 phospholipids, as the last group was reported for the first time. The major components among them were—monounsaturated eicosenoic and oleic acids, β-sitosterol, β-tocopherol, and phosphatidylcholine. The in vitro tests demonstrated DNA protective activity and a lack of cytotoxicity of the oil, data that has been reported for the first time. The in vitro MTT test of the oil on HT-29 and PC3 cell lines did not indicate antitumor activity. The seed oil studied contains valuable bio-components, which have proven benefits for human health, and that is why it could be used in food, cosmetic, and pharmaceutical products.
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Positional isomers of hexadecenoic acid are considered as fatty acids with anti-inflammatory properties. The best known of them, palmitoleic acid (cis-9-hexadecenoic acid, 16:1n-7), has been identified as a lipokine with important beneficial actions in metabolic diseases. Hypogeic acid (cis-7-hexadecenoic acid, 16:1n-9) has been regarded as a possible biomarker of foamy cell formation during atherosclerosis. Notwithstanding the importance of these isomers as possible regulators of inflammatory responses, very little is known about the regulation of their levels and distribution and mobilization among the different lipid pools within the cell. In this work, we describe that the bulk of hexadecenoic fatty acids found in mouse peritoneal macrophages is esterified in a unique phosphatidylcholine species, which contains palmitic acid at the sn-1 position, and hexadecenoic acid at the sn-2 position. This species markedly decreases when the macrophages are activated with inflammatory stimuli, in parallel with net mobilization of free hexadecenoic acid. Using pharmacological inhibitors and specific gene-silencing approaches, we demonstrate that hexadecenoic acids are selectively released by calcium-independent group VIA phospholipase A2 under activation conditions. While most of the released hexadecenoic acid accumulates in free fatty acid form, a significant part is also transferred to other phospholipids to form hexadecenoate-containing inositol phospholipids, which are known to possess growth-factor-like-properties, and are also used to form fatty acid esters of hydroxy fatty acids, compounds with known anti-diabetic and anti-inflammatory properties. Collectively, these data unveil new pathways and mechanisms for the utilization of palmitoleic acid and its isomers during inflammatory conditions, and raise the intriguing possibility that part of the anti-inflammatory activity of these fatty acids may be due to conversion to other lipid mediators.
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Recently, nutraceutical bioactive compounds in foods have been discovered for their potential health benefits regarding the prevention of chronic disorders, such as cancer, and inflammatory, cardiovascular, and metabolic diseases. Dietary omega-3 polyunsaturated fatty acids (ω-3PUFAs), including alpha-linolenic acid, docosapentaenoic acid, and eicosapentaenoic acid, are mostly attractive. They are available for the customers worldwide from commonly used foods and/or as components of commercial food supplements. The anti-inflammatory and hypotriglyceridemic effects of these fatty acids are well known, whereas pro-inflammatory properties have been recognized in their dietary counterparts, the ω-6PUFAs. Both ω-3 and ω-6PUFAs contribute to the production of lipid mediators such as endocannabinoids that are notably involved in control of food intake, energy sensing, and food-related disorders. In this review, we present ω-3 and ω-6PUFAs and their derivatives, endocannabinoids; discuss the anti-obesity effects of ω-3PUFAs; their roles in inflammation and colorectal cancer development; and how their action can be co-preventative and co-therapeutic.
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Background: The effects of different types of fatty acids on the gene expression of key players in the IRS1/PI3K signaling pathway have been poorly studied. Material and methods: We analyzed IRS1, p85α, and p110β mRNA expression and the fatty acid composition of phospholipids in visceral adipose tissue from patients with morbid obesity and from non-obese patients. Moreover, we analyzed the expression of those genes in visceral adipocytes incubated with oleic, linoleic, palmitic and dosahexaenoic acids. Results: We found a reduced IRS1 expression in patients with morbid obesity, independent of insulin resistance, and a reduced p110β expression in those with lower insulin resistance. A positive correlation was found between p85α and stearic acid, and between IRS1 and p110β with palmitic and dosahexaenoic acid. In contrast, a negative correlation was found between p85α and oleic acid, and between IRS1 and p110β with linoleic, arachidonic and adrenic acid. Incubation with palmitic acid decreased IRS1 expression. p85α was down-regulated after incubation with oleic and dosahexaenoic acid and up-regulated with palmitic acid. p110β expression was increased and decreased after incubation with oleic and palmitic acid, respectively. The ratio p85α/p110β was decreased by oleic and dosahexaenoic acid and increased by palmitic acid. Conclusions: Our in vitro results suggest a detrimental role of palmitic acid on the expression of gene related to insulin signaling pathway, with oleic acid being the one with the higher and more beneficial effects. DHA had a slight beneficial effect. Fatty acid-induced regulation of genes related to the IRS1/PI3K pathway may be a novel mechanism by which fatty acids regulate insulin sensitivity in visceral adipocytes.
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Inflammatory bowel disease (IBD) is a multifactorial intestinal disorder characterized by chronic intestinal inflammation. The etiology of IBD is still unclear, although genetic, environmental and host factors have been associated to the disease. Extra-virgin olive oil (EVO) is a central component of the Mediterranean diet and it decreases chronic inflammation by interfering with arachidonic acid and NF-κB signaling pathways. Specifically, the different components of EVO are able to confer advantages in terms of health in their site of action. For instance, oleic acid displays a protective effect in liver dysfunction and gut inflammation, whereas phenolic compounds protect colon cells against oxidative damage and improve the symptoms of chronic inflammation in IBD. Given the biological properties of EVO, we investigated whether its administration is able to confer protection in a mouse model of dextrane sodium sulfate (DSS)-induced colitis. Four EVO cultivars from the Apulian Region of Italy, namely Ogliarola (Cima di Bitonto), Coratina, Peranzana and Cima di Mola, respectively, were used. Administration of EVO resulted in reduced body weight loss in our colitis model. Furthermore, mice treated with Ogliarola, Coratina and Cima di Mola EVO displayed a reduction of rectal bleeding and IL-1β, TGFβ, IL-6 gene expression levels. Furthermore, Ogliarola, Coratina and Peranzana EVO administration ameliorated intestinal permeability and histopathological features of inflammation. Our data further validate the well-known positive effects of EVO supplementation in promoting human health and suggest the bona fide contribution of EVO in preventing onset and reducing progression of intestinal inflammation.
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Background: Diets based on meat products are not recommended in the case of ulcerative colitis (UC). The objective here is to test if some traditional cured meat products, as acorn-fed ham (high levels of oleic acid), may be useful for controlling inflammatory diseases as UC in animal models, which could represent a new dietary complementary intervention in the prevention of this inflammatory disease in humans. Methods: Two rat cohorts have been used: conventional vegetable rat feed and acorn-fed ham. UC was induced with DSS in drinking water ad libitum for 1 week. Short-chain fatty acids (SCFAs) and 16S rRNA metagenomics from bacterial populations were analyzed in cecum samples. Colon samples were analyzed for histological parameters. Results: Acorn-fed ham diet induced changes in gut microbiota composition, with pronounced enrichments in anti-inflammatory bacterial genera (Alistipes, Blautia, Dorea, Parabacteroides). The animals with this diet showed a strong reduction in most parameters associated to ulcerative colitis: disease activity index, macroscopic score of colitis, epitelium alteration in colon mucosa, inflammatory cell density in colon, myeloperoxidase titers in colon, proinflammatory cytokines (IL-17, IFN-γ). Also, acorn-fed ham diet animals showed increased total antioxidant activity an oleic acid levels in plasma, as well as higher short-chain fatty acid concentrations in cecum (isobutyric, isovaleric and valeric). Conclusions: In the acorn-fed ham cohort, as a result of the dietary intake of oleic acid and low intake of omega-6 fatty acids, a strong preventive effect against UC symptoms was observed.
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Background: Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the anti-inflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition. Results: The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the ex vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles. Conclusions: Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.
Immune regulation has an important role in cancer development, particularly in organs with continuous exposure to environmental pathogens, such as the liver and gastrointestinal tract. Chronic liver inflammation can lead to the development of hepatobiliary cancers, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), or combined HCC (cHCC)-CCA. In this review, we discuss the link between oxidative stress and the hepatic immune compartments, as well as how these factors trigger hepatocyte damage, proliferation, and eventually cancer initiation and its sustainment. We further give an overview of new anticancer therapies based on immunomodulation.
Neurodegenerative diseases (ND) are characterised by loss of neurons in the brain and spinal cord. For the normal functioning of the brain, divers group of fatty acids in the form of glycerophospholipids, glycerol ether lipids, cerebrosides, sulfatides, and gangliosides are essential. They are present abundantly in the nervous system and are actively involved in both the development and maintenance of the nervous system. A dietary deficiency of essential fatty acid during development results in hypomyelination state which affects various neuronal functions. Several studies suggested that age remains the primary risk factor for almost all neurodegenerative disorders. The potential contribution of these fatty acids in the progression of neurodegenerative disorders is indispensable. Erucic acid an omega 9 fatty acid, which is obtained from edible oils has proven to cause myocardial lipidosis, heart lesions and hepatic steatosis in animals therefore, its content in edible oils is restricted to certain levels by regulatory agencies. However, erucic acid in the form of a mixture with oleic acid is often used as a dietary treatment for the management of adrenoleukodystrophy without any cardiotoxicity. Our literature search revealed that, erucic acid reported to enhance cognitive function, interact with peroxisome proliferator activated receptors (PPARs), inhibit elastase and thrombin. In this review first we have attempted to describe the relationship between fatty acids and neurodegeneration followed by a description on the pharmacology of erucic acid. The overall purpose of this review is to analyse toxic and beneficial neuropharmacological effects of erucic acid.
Background & aims There has been controversial evidence regarding the relationship between isomers of circulating trans-fatty acids (TFAs) and mortality. This study aimed to ascertain the relationships between plasma TFAs and overall or cause-specific mortality of the general population in two independent subsets from the US National Health and Nutrition Examination Survey (1999-2000 and 2009-2010 cycles). Methods and results Plasma TFA isomers (C16:1n-7t, C18:1n-7t, C18:1n-9t and C18:2n-6,9t) in 3439 adults free of cancer or severe cardiovascular disease were analyzed by gas chromatography/mass spectrometry. Overall, 259 died among 1376 individuals over a median follow-up of 15.6 years in the 1999-2000 cycle, and 105 died in the latter subset of 2063 subjects during a median of 5.9 years. Cox proportional hazards regression was conducted to estimate the hazard ratios of mortality. Elaidic acid (C18:1n-9t) was considerably associated with long-term total mortality in the 1999-2000 cycle after adjusting for confounders, with a 54% increase in the top tertile compared with the bottom one. However, the association disappeared with halving C18:1n-9t by 2009-2010. In contrast, neither of the ruminant-derived TFAs (C16:1n-7t and C18:1n-7t) suggested any inverse correlations with all-cause death, mortality due to heart disease, cancer or other causes. Conclusion The major isomer of industrial TFAs, the higher circulating C18:1n-9t might be associated with increased long-term mortality. The associations with death risk turned slight with the reduction of TFAs consumption by half. However, dietary guidelines should rigorously identify the healthy effect of animal TFAs consumption.
In this review study, we focus on potential benefits of the transcription factor PPARδ and its ligand erucic acid (EA) in management of neuroectodermal tumors and Parkinson's Disease. PPARδ is a nuclear receptor and transcription factor that induces myelination, promotes oligodendroglial and neuronal differentiation, and possess anti-neuroinflammatory properties. While both pro-tumorigenic and anti-tumorigenic effects have been described for PPARδ, we propose that PPARδ may perform a predominantly anticancer role in tumors originating from the neuroectoderm. PPARδ ligand-activation via oleic acid and GW501516, or overexpression of PPARδ, elicits profound antitumor actions in neuroblastoma and melanoma. In glioblastomas, there is evidence indicating a differentiation failure of O2A (oligodendroglial-astrocytic biprogenitor) cells and it has been shown that EA reduced DNA synthesis in C6 rat glioblastoma spheroid cultures in clinically achievable concentrations. EA is a ω9 fatty acid which is being used in the treatment of adrenoleukodystrophy. EA is widely consumed in Asian countries via ingestion of cruciferous vegetables including mustard and rapeseed oil. EA also exerts antioxidant and anti-inflammatory activities. Recent studies of Parkinson's Disease (PD) have implicated demyelination, white matter pathology, oligodendroglial injury, and neural inflammation in the underlying pathophysiology. In the rotenone PD model in rats, PPARδ ligand GW501516 saves dopaminergic neurons during injury induced by chemical toxins and improves behavioral functioning in PD via alleviation of endoplasmic reticulum stress. PPARδ agonists also reduce the NLRP3 inflammasome-associated neural inflammation in the MPTP PD model in mice. Herein, we propose that PPARδ and its ligand EA highly deserve to be studied in animal models of neuroblastoma, glioblastoma, and PD.