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![Choline inhibits TNF release (A) and NF-κB activation (B) in endotoxinstimulated RAW-264.7 mouse macrophagelike cells. (A) RAW cells were exposed to the indicated concentration of choline 10 min prior to the addition of endotoxin (4 ng/mL). Culture supernatants were harvested 4 h later and TNF was determined by ELISA. Data represent the mean ± SEM of two representative experiments conducted in duplicate (*P < 0.04 as compared, with vehicle [V] treated controls). (B) RAW cells were exposed to the indicated concentrations of choline 10 min prior to the addition of endotoxin (4 ng/mL) and cells were harvested 2 h after endotoxin challenge for determination of NF-κB activation by EMSA. Autoradiographs were subjected to densitometry by using Quantity One software (Biorad). Data represent the mean ± SEM of three independent experiments (*P < 0.04, **P < 0.006 as compared with the lowest choline concentration tested).](profile/Mauricio-Rosas-Ballina/publication/5272185/figure/fig3/AS:667629815615495@1536186760351/Choline-inhibits-TNF-release-A-and-NF-kB-activation-B-in-endotoxinstimulated.png)
Choline inhibits TNF release (A) and NF-κB activation (B) in endotoxinstimulated RAW-264.7 mouse macrophagelike cells. (A) RAW cells were exposed to the indicated concentration of choline 10 min prior to the addition of endotoxin (4 ng/mL). Culture supernatants were harvested 4 h later and TNF was determined by ELISA. Data represent the mean ± SEM of two representative experiments conducted in duplicate (*P < 0.04 as compared, with vehicle [V] treated controls). (B) RAW cells were exposed to the indicated concentrations of choline 10 min prior to the addition of endotoxin (4 ng/mL) and cells were harvested 2 h after endotoxin challenge for determination of NF-κB activation by EMSA. Autoradiographs were subjected to densitometry by using Quantity One software (Biorad). Data represent the mean ± SEM of three independent experiments (*P < 0.04, **P < 0.006 as compared with the lowest choline concentration tested).
Source publication
The alpha7 subunit-containing nicotinic acetylcholine receptor (alpha7nAChR) is an essential component in the vagus nerve-based cholinergic anti-inflammatory pathway that regulates the levels of TNF, high mobility group box 1 (HMGB1), and other cytokines during inflammation. Choline is an essential nutrient, a cell membrane constituent, a precursor...
Contexts in source publication
Context 1
... cells were pre-incubated for 10 min with in- creasing choline concentrations prior to endotoxin activation. As shown in Fig- ure 1A, choline dose-dependently sup- pressed endotoxin-stimulated TNF re- lease from RAW cells. NF-κB is a key transcription factor that is activated in response to endotoxin for the production of inflammatory mediators such as TNF. ...
Context 2
... ex- tracts were prepared and electrophoretic mobility shift assays (EMSA) were con- ducted to measure activated NF-κB. Choline dose-dependently suppressed NF-κB activation in response to endo- toxin ( Figure 1B). ...
Context 3
... and in vivo and improves survival of mice with polymicrobial sepsis. Based on our data that choline suppresses TNF release and NF-κB activation in RAW cells (see Figure 1A,1B), we tested whether choline also attenuates HMGB1 release from RAW cells. Choline dose- dependently reduced HMGB1 release from endotoxin-stimulated RAW cells ( Figure 4A). ...
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Previous reports have indicated that artificial stimulation of the vagus nerve reduces systemic inflammation in experimental models of sepsis. This phenomenon is a part of a broader cholinergic anti-inflammatory pathway which activates the vagus nerve to modulate inflammation through activation of alpha7 nicotinic acetylcholine receptors (α7nACHR)....
Nicotine stimulation of α7 nicotinic acetylcholine receptor (α7 nAChR) powerfully inhibits pro-inflammatory cytokine production in lipopolysaccharide (LPS)-stimulated macrophages and in experimental models of endotoxemia. A signaling pathway downstream from the α7 nAChRs, which involves the collaboration of JAK2/STAT3 and NF-κB to interfere with si...
Background
Caspase-11, a cytosolic receptor of bacterial endotoxin (lipopolysaccharide: LPS), mediates immune responses and lethality in endotoxemia and experimental sepsis. However, the upstream pathways that regulate caspase-11 activation in endotoxemia and sepsis are not fully understood. The aim of this study is to test whether TIR-domain-conta...
Citations
... Recently, so-called anti-inflammatory neuroendocrine-immune circuits have gained considerable attention, and it has become evident that allergic inflammatory diseases are characterized by altered cholinergic signaling [26][27][28][29]. The nicotinergic acetylcholine receptor alpha 7 (Chrna7) downregulates tumor necrosis factor alpha (TNFα) production by macrophages [30] and was also found on MC [31][32][33]. Activation of Chrna7 was shown to downregulate MC inflammatory responses and hence to establish resilience against hyperinflammatory responses [32]. ...
Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators such as nerve growth factor (NGF) and substance P (SP). Mast cell proteases (MCPs) and cholinergic factors (Chrna7, SLURP1) were recently described to modulate MC stress response. We studied MCPs and Chrna7/SLURP1 and their interplay in a mouse model for noise induced stress (NiS) and atopic dermatitis-like allergic inflammation (AlD) and in cultured MC lacking Chrna7. We found that the cholinergic stress axis interacts with neuroendocrine stress mediators and stress-mediator cleaving enzymes in AlD. SP-cleaving mMCP4+ MC were upregulated in AlD and further upregulated by stress in NiS+AlD. Anti-NGF neutralizing antibody treatment blocked the stress-induced upregulation in vivo, and mMCP4+ MCs correlated with measures of AlD disease activity. Finally, high mMCP4 production in response to SP depended on Chrna7/SLURP1 in cultured MCs. In conclusion, mMCP4 and its upstream regulation by Chrna7/SLURP1 are interesting novel targets for the treatment of allergic inflammation and its aggravation by stress.
... This seems reasonable, as catecholamines have been shown to act on β adrenoceptors on T cells to increase ACh synthesis and release by promoting ChAT gene expression via cAMP/PKA pathways [79,80] (see Section 4.1.3). These findings and the accumulated evidence indicate that stimulation of α7 nAChRs by ACh derived from T cells induces activation of the JAK2/STAT3 signaling cascade in macrophages and inhibits NF-κB-mediated activation of TNF-α transcription, resulting in inhibition of TNF-α synthesis [137,138]. ...
Loewi’s discovery of acetylcholine (ACh) release from the frog vagus nerve and the discovery by Dale and Dudley of ACh in ox spleen led to the demonstration of chemical transmission of nerve impulses. ACh is now well-known to function as a neurotransmitter. However, advances in the techniques for ACh detection have led to its discovery in many lifeforms lacking a nervous system, including eubacteria, archaea, fungi, and plants. Notably, mRNAs encoding choline acetyltransferase and muscarinic and nicotinic ACh receptors (nAChRs) have been found in uninnervated mammalian cells, including immune cells, keratinocytes, vascular endothelial cells, cardiac myocytes, respiratory, and digestive epithelial cells. It thus appears that non-neuronal cholinergic systems are expressed in a variety of mammalian cells, and that ACh should now be recognized not only as a neurotransmitter, but also as a local regulator of non-neuronal cholinergic systems. Here, we discuss the role of non-neuronal cholinergic systems, with a focus on immune cells. A current focus of much research on non-neuronal cholinergic systems in immune cells is α7 nAChRs, as these receptors expressed on macrophages and T cells are involved in regulating inflammatory and immune responses. This makes α7 nAChRs an attractive potential therapeutic target.
... Both choline and betaine have demonstrated anti-inflammatory properties. For instance, a study revealed that injecting mice with 50 mg/kg of choline intraperitoneally prior to LPS administration resulted in reduced systemic levels of TNF [35]. Additionally, the same authors demonstrated that choline inhibited TNF release in human macrophages. ...
Mastitis is a significant infectious disease in dairy cows, resulting in milk yield loss and culling. Early detection of mastitis-prone cows is crucial for implementing effective preventive measures before disease onset. Current diagnosis of subclinical mastitis (SCM) relies on somatic cell count assessment post-calving, lacking predictive capabilities. This study aimed to identify metabolic changes in pre-SCM cows through targeted metabolomic analysis of urine samples collected 8 wks and 4 wks before calving, using mass spectrometry. A nested case-control design was employed, involving a total of 145 multiparous dairy cows, with disease occurrence monitored pre- and postpartum. Among them, 15 disease-free cows served as healthy controls (CON), while 10 cows exclusively had SCM, excluding those with additional diseases. Urinary metabolite profiling revealed multiple alterations in acylcarnitines, amino acids, and organic acids in pre-SCM cows. Metabotyping identified 27 metabolites that distinguished pre-SCM cows from healthy CON cows at both 8 and 4 wks before parturition. However, only four metabolites per week showed significant alterations (p < 0.005). Notably, a panel of four serum metabolites (asymmetric dimethylarginine, proline, leucine, and homovanillate) at 8 wks prepartum, and another panel (asymmetric dimethylarginine, methylmalonate, citrate, and spermidine) at 4 wks prepartum, demonstrated predictive ability as urinary biomarkers for SCM risk (AUC = 0.88; p = 0.02 and AUC = 0.88; p = 0.03, respectively). In conclusion, our findings indicate that metabolite testing can identify cows at risk of SCM as early as 8 and 4 wks before parturition. Validation of the two identified metabolite panels is warranted to implement these predictive biomarkers, facilitate early intervention strategies, and improve dairy cow management to mitigate the impact of SCM. Further research is needed to confirm the efficacy and applicability of these biomarkers in practical farm settings.
... [46]. TNF-α is mainly produced by macrophages and is regulated by several subcellular pathways involving α7-nAChR in an auto-and paracrine fashion [47,48]. Indeed, in wild-type mice, it has been shown that vagus nerve stimulation decreases the release of LPSinduced TNF-α release and that this effect is abolished in α7 knock-out mice [49]. ...
There is growing evidence that autoantibodies (AAbs) against proteins expressed in the brain are playing an important role in neurological and psychiatric disorders. Here, we explore the presence and the role of peripheral AAbs to the α7-nicotinic acetylcholine receptor (nAChR) in inflammatory subgroups of psychiatric patients with bipolar disorder (BD) or schizophrenia (SCZ) and healthy controls. We have identified a continuum of AAb levels in serum when employing a novel ELISA technique, with a significant elevation in patients compared to controls. Using unsupervised two-step clustering to stratify all the subjects according to their immuno-inflammatory background, we delineate one subgroup consisting solely of psychiatric patients with severe symptoms, high inflammatory profile, and significantly increased levels of anti-nAChR AAbs. In this context, we have used monoclonal mouse anti-human α7-nAChR antibodies (α7-nAChR-mAbs) and shown that TNF-α release was enhanced upon LPS stimulation in macrophages pre-incubated with α7-nAChR-mAbs compared to the use of an isotype control. These findings provide a basis for further study of circulating nicotinic AAbs, and the inflammatory profile observed in patients with major mood and psychotic disorders.
... Since pioneer studies in 2000, showed the decrease in inflammation followed by VNS in rats (Borovikova et al., 2000), multiple studies in animal models were performed showing that VNS decreases inflammation and mitigates disease in acute inflammatory conditions such as endotoxemia, sepsis, hemorrhagic shock, postoperative ileus, and kidney ischemia-reperfusion injury [for a review see Kelly et al., 2022] and in chronic inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease (IBD) and asthma (Levine et al., 2014;Yuan and Silberstein, 2016;Wheless et al., 2018;Austelle et al., 2022). The mechanisms have been under debate and accepted statements include the regulation of cytokine production through the nicotinic acetylcholine receptor subunit α7 (α7nAchR) in the spleen, termed "the cholinergic antiinflammatory pathway" (Wang et al., 2003;Gallowitsch-Puerta and Pavlov, 2007;Parrish et al., 2008), through second-order vagal projections (indirect) (Ackerman et al., 1987;Berthoud and Powley, 1993) and first-order (direct pathway) vagus nerve-spleen . Another important landmark for the bioelectronic targeting of the vagal anti-inflammatory reflex has been the clinical testing of VNS devices for patients with inflammatory and autoimmune disorders, such as rheumatoid arthritis and IBD, with decreased inflammation and positive clinical outcomes (Koopman et al., 2016;Genovese et al., 2020). ...
Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies. Given the emergency of accelerating the progress in new neuromodulation treatments (i.e., drug-resistant hypertension, autoimmune and degenerative diseases), collaboration between multiple fields is imperative. This work intends to foster multidisciplinary work and bring together different fields to provide the fundamental basis underlying Bioelectronic Medicine. In this review we will go from the biophysics of the cell membrane, which we consider the inner core of neuromodulation, to patient care. We will discuss the recently discovered mechanism of neurotransmission switching and how it will impact neuromodulation design, and we will provide an update on neuronal and glial basis in health and disease. The advances in biomedical technology have facilitated the collection of large amounts of data, thereby introducing new challenges in data analysis. We will discuss the current approaches and challenges in high throughput data analysis, encompassing big data, networks, artificial intelligence, and internet of things. Emphasis will be placed on understanding the electrochemical properties of neural
... The α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages and other immune cells has been identified as a key mediator of cholinergic anti-inflammatory signaling [6,7]. Stimulation of the α7nAChR on macrophages activates downstream intracellular mechanisms, including suppression of NF-κB activation and results in decreased production of TNF and other pro-inflammatory cytokines [8][9][10][11]. These discoveries opened an avenue of preclinical research revealing the anti-inflammatory efficacy of vagus nerve stimulation (VNS) and α7nAChR agonists in endotoxemia, sepsis and many other inflammatory conditions [12,13]. ...
... The anti-inflammatory effects of α7nAChR activation using small molecule agonists have been extensively studied in mice with endotoxemia and CLP [9,18,19]. For instance, administering a partially selective α7nAChR agonist, GTS-21, or choline-a product of acetylcholine degradation and a selective endogenous α7nAChR agonist suppresses circulating pro-inflammatory cytokine levels, which is linked to reduced NF-κB activation and increased survival in endotoxic mice and rates [11,19]. ...
Background
The involvement of the autonomic nervous system in the regulation of inflammation is an emerging concept with significant potential for clinical applications. Recent studies demonstrate that stimulating the vagus nerve activates the cholinergic anti-inflammatory pathway that inhibits pro-inflammatory cytokines and controls inflammation. The α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages plays a key role in mediating cholinergic anti-inflammatory effects through a downstream intracellular mechanism involving inhibition of NF-κB signaling, which results in suppression of pro-inflammatory cytokine production. However, the role of the α7nAChR in the regulation of other aspects of the immune response, including the recruitment of monocytes/macrophages to the site of inflammation remained poorly understood.
Results
We observed an increased mortality in α7nAChR-deficient mice (compared with wild-type controls) in mice with endotoxemia, which was paralleled with a significant reduction in the number of monocyte-derived macrophages in the lungs. Corroborating these results, fluorescently labeled α7nAChR-deficient monocytes adoptively transferred to WT mice showed significantly diminished recruitment to the inflamed tissue. α7nAChR deficiency did not affect monocyte 2D transmigration across an endothelial monolayer, but it significantly decreased the migration of macrophages in a 3D fibrin matrix. In vitro analysis of major adhesive receptors (L-selectin, β1 and β2 integrins) and chemokine receptors (CCR2 and CCR5) revealed reduced expression of integrin αM and αX on α7nAChR-deficient macrophages. Decreased expression of αMβ2 was confirmed on fluorescently labeled, adoptively transferred α7nAChR-deficient macrophages in the lungs of endotoxemic mice, indicating a potential mechanism for α7nAChR-mediated migration.
Conclusions
We demonstrate a novel role for the α7nAChR in mediating macrophage recruitment to inflamed tissue, which indicates an important new aspect of the cholinergic regulation of immune responses and inflammation.
... Choline, a precursor of ACh, enhances cholinergic activity by directly interacting with cholinergic receptors at high concentrations [7]. Several studies showed that activation of CAP by choline via α7nAChRs reduces the levels of pro-inflammatory factors from endotoxin-induced mononuclear cells via nuclear factor kappa B (NF-κB) pathway [8]. ...
... The effects of drug treatments on cell viability were examined by applying increasing concentrations of choline and KYNA by MTT assay (n=5, A015, ABP Biosciences, China). Firstly, increasing concentrations of LPS (Escherichia coli, Sigma Aldrich L4130 0111: B4; in μg/mL 1-3 and 10) were applied, and COX-2 expression and PGE 2 levels were analyzed to establish the effective concentration [8]. Secondly, pretreatment of increasing concentrations of choline chloride (Sigma-Aldrich C7017) (in μM: 1-3-10-30) 30 min before LPS administration applied to establish the effective concentration of choline on LPS-induced parameters. ...
... The anti-inflammatory effects α7nAChR agonists have been widely investigated in LPS-stimulated RAW264.7 cells in vitro [5,8]. Earlier, significant decrease in proinflammatory cytokine levels including TNF-α, interleukins (IL-1β, -6, -18) and HMGB1 by α7nAChR-mediated activation of CAP in LPS-activated macrophages suggested that α7nAChRs would be identified as target receptors in the treatment of inflammatory conditions [6]. ...
Objectives
Inflammation can be endogenously modulated by the cholinergic anti-inflammatory pathway via calcium (Ca ²⁺ )-permeable alpha-7 nicotinic acetylcholine receptor (α7nAChR) ion channel expressed in immune cells. α7nAChR agonist choline and tryptophan metabolite kynurenic acid (KYNA) produces immunomodulatory effects. This study aimed to determine the effects of the choline and KYNA on the lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 pathway.
Methods
In vitro inflammation model was produced via LPS administration in macrophage cells. To determine the effective concentrations, choline and KYNA were applied with increasing concentrations and LPS-induced inflammatory parameters investigated. The involvement of nAChR mediated effects was investigated with the use of non-selective nAChR and selective α7nAChR antagonists. The effects of choline and KYNA on COX-2 enzyme, PGE 2 , TNFα, NF-κB and intracellular Ca ²⁺ levels were analyzed.
Results
LPS-induced COX-2 expression, PGE 2 TNFα and NF-κB levels were decreased with choline treatment while intracellular calcium levels via α7nAChRs increased. KYNA also showed an anti-inflammatory effect on the same parameters. Additionally, KYNA administration increased the effectiveness of choline on these inflammatory mediators.
Conclusions
Our data suggest a possible interaction between the kynurenine pathway and the cholinergic system on the modulation of LPS-induced inflammatory response in macrophages.
... This receptor is a ligand-gated ion channel and is composed of five α7 subunits that, upon activation, initiate the cholinergic anti-inflammatory pathway (CAP) [18]. Several preclinical studies have shown that activation of CAP attenuates inflammatory conditions, including arthritis, ulcerative colitis, and sepsis [19][20][21]. Furthermore, in a murine model of AAA, the activation of α7nAChRs by a cholinergic agonist prevented AAA progression by a mechanism associated with the suppression of pro-inflammatory cytokines and the inhibition of vascular smooth muscle cell pyroptosis, mediated by inflammasome 3 and thereby a reduction in MMP activity [22]. ...
Inflammation and elastin degradation are key hallmarks in the pathogenesis of abdominal aortic aneurysms (AAAs). It has been acknowledged that activation of alpha7 nicotinic acetylcholine receptors (α7nAChRs) attenuates inflammation, termed the cholinergic anti-inflammatory pathway (CAP). Thus, we hypothesize that low-dose nicotine impairs the progression of elastase-induced AAAs in rats by exerting anti-inflammatory and anti-oxidative stress properties. Male Sprague–Dawley rats underwent surgical AAA induction with intraluminal elastase infusion. We compared vehicle rats with rats treated with nicotine (1.25 mg/kg/day), and aneurysm progression was monitored by weekly ultrasound images for 28 days. Nicotine treatment significantly promoted AAA progression (p = 0.031). Additionally, gelatin zymography demonstrated that nicotine significantly reduced pro-matrix metalloproteinase (pro-MMP) 2 (p = 0.029) and MMP9 (p = 0.030) activity in aneurysmal tissue. No significant difference was found in the elastin content or the score of elastin degradation between the groups. Neither infiltrating neutrophils nor macrophages, nor aneurysmal messenger RNA (mRNA) levels of pro- or anti-inflammatory cytokines, differed between the vehicle and nicotine groups. Finally, no difference in mRNA levels of markers for anti-oxidative stress or the vascular smooth muscle cells’ contractile phenotype was observed. However, proteomics analyses of non-aneurysmal abdominal aortas revealed that nicotine decreased myristoylated alanine-rich C-kinase substrate and proteins, in ontology terms, inflammatory response and reactive oxygen species, and in contradiction to augmented AAAs. In conclusion, nicotine at a dose of 1.25 mg/kg/day augments AAA expansion in this elastase AAA model. These results do not support the use of low-dose nicotine administration for the prevention of AAA progression.
... The effective contribution of α7nAChRs to the anti-inflammatory response was demonstrated using several α7nAChR agonists. Treatment with choline or GTS-21 improves survival of mice after CLP or LPS-induced endotoxemia [105,106]. Interestingly, choline administration 24 h after CLP-induced polymicrobial sepsis still significantly improved survival in mice, showing high impact of the CAP. In agreement with these results, activation of α7nAChRs by nicotine enhances survival in sepsis-induced ALI induced by instilling E. coli into the airways. ...
The α7-nicotinic acetylcholine receptor (α7nAChR) is a key protein in the cholinergic anti-inflammatory pathway (CAP) that links the nervous and immune systems. Initially, the pathway was discovered based on the observation that vagal nerve stimulation (VNS) reduced the systemic inflammatory response in septic animals. Subsequent studies form a foundation for the leading hypothesis about the central role of the spleen in CAP activation. VNS evokes noradrenergic stimulation of ACh release from T cells in the spleen, which in turn activates α7nAChRs on the surface of macrophages. α7nAChR-mediated signaling in macrophages reduces inflammatory cytokine secretion and modifies apoptosis, proliferation, and macrophage polarization, eventually reducing the systemic inflammatory response. A protective role of the CAP has been demonstrated in preclinical studies for multiple diseases including sepsis, metabolic disease, cardiovascular diseases, arthritis, Crohn's disease, ulcerative colitis, endometriosis, and potentially COVID-19, sparking interest in using bioelectronic and pharmacological approaches to target α7nAChRs for treating inflammatory conditions in patients. Despite a keen interest, many aspects of the cholinergic pathway are still unknown. α7nAChRs are expressed on many other subsets of immune cells that can affect the development of inflammation differently. There are also other sources of ACh that modify immune cell functions. How the interplay of ACh and α7nAChR on different cells and in various tissues contributes to the anti-inflammatory responses requires additional study. This review provides an update on basic and translational studies of the CAP in inflammatory diseases, the relevant pharmacology of α7nAChR-activated drugs and raises some questions that require further investigation.
... Aside from SM, milk-derived choline moieties dose-dependently decreased Tnf-α production due to inhibition of NF-κB activation in endotoxin treated RAW macrophage-like cells [156]. When administered to mice intraperitoneally prior to endotoxin treatment, choline (50 mg/kg) improved survival and decreased plasma TNF-α [156]. ...
... Aside from SM, milk-derived choline moieties dose-dependently decreased Tnf-α production due to inhibition of NF-κB activation in endotoxin treated RAW macrophage-like cells [156]. When administered to mice intraperitoneally prior to endotoxin treatment, choline (50 mg/kg) improved survival and decreased plasma TNF-α [156]. Indeed, similar anti-inflammatory findings have been reported for polar lipids of marine origin in macrophage cell culture models [157,158]. ...
Background
Milk contains polar lipids may confer health benefits upon consumption. Therefore, polar lipids have received considerable attention for development in the nutraceutical and pharmaceutical space. We review the prophylactic and therapeutic potential of milk polar lipids and their current market trends.
Methods
The following databases were used to retrieve articles for this narrative review: SCOPUS, ScienceDirect, PubMed, and Google Scholar. The search criteria included the following keywords and synonyms combined: (“milk polar lipids” or “milk phospholipids” or “milk glycerophospholipids” or “milk sphingolipids”) AND (“anti-inflammatory” or “cardiovascular” or “cancer” or “cognitive health” or “nutraceutical” or “pharmaceutical” or “supplement”).
Results
Milk polar lipid supplementation appears to improve cognitive health in both child development and age-associated cognitive decline. Milk polar lipids modulate cardiovascular risk factors including lipid levels, inflammation, and platelet function in preclinical studies, but evidence is limited in humans. Milk polar lipids may also affect colon cancer pathogenesis through anti-inflammatory mechanisms. Polar lipids are gaining attention in the nutraceutical and pharmaceutical space for their use in the development of novel therapeutics and pharmaceutical delivery systems.
Conclusions
Milk polar lipids exhibit a multitude of health benefits that may be of value in the nutraceutical and pharmaceutical industries as reflected in current market and research trends for the use of polar lipids and the development of products targeting infant cognitive development, cognitive decline in the aged, cardiovascular diseases, and cancer. Further clinical studies are required to assess efficacy and safety of milk polar lipid supplementation in human diseases.
