Uncovering the pleiotropic effects of oleoylethanolamide on obesity-driven chronic kidney disease in mice.

Transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) has previously been established as an effective model for replicating early brain inflammation triggered by acute hypoperfusion and subsequent reperfusion events. Recognizing the significant role of diet and nutrition in shaping brain neuroplasticity, this investigation explored the neuroprotective impact of kaempferol (KAM), a dietary flavonoid, within a rat BCCAO/R paradigm. Adult Wistar rats received a single oral dose of KAM (40 mg) 6 h prior to surgery. Extensive lipidomic and molecular assessments were performed on frontal and temporal-occipital cortical tissues in addition to plasma samples. In the frontal cortex, KAM treatment led to increased concentrations of anti-inflammatory N-acylethanolamines – namely palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHAEA) – while diminishing levels of oxidized arachidonic acid derivatives. KAM further suppressed cyclooxygenase-2 (COX-2) protein and selectively reduced the endocannabinoid 2-arachidonoylglycerol (2-AG), reflecting alterations in arachidonic acid metabolism. These molecular effects were accompanied by elevated peroxisome proliferator-activated receptor alpha (PPARα) and cannabinoid receptors CB1R and CB2R, supporting activation of anti-inflammatory pathways at both nuclear and membrane levels. No marked changes emerged in the temporal-occipital cortex. In plasma, DHAEA levels increased in parallel with cortical findings, whereas PEA and OEA elevations were restricted to shamoperated KAM-treated subjects, implying potential central redistribution during hypoperfusion/reperfusion stress. Collectively, these results indicate that KAM confers anti-inflammatory protection by both suppressing COX-2- mediated prostanoid production and enhancing PPARα-dependent lipid signaling. This dual mechanism underscores KAM’s promise as a dietary strategy to mitigate neuroinflammation following hypoperfusion– reperfusion injury.

To investigate the endocannabinoid system (ECS) and affective state responses to acute aerobic exercise in adult cancer patients versus their healthy peers. Participants engaged in 30min of quiet rest followed by 30min of exercise. Exercise involved 5-min warm-up/cool-down procedures and 20min of moderate-intensity training (64-76% of age-predicted maximal heart rate) on a treadmill or cycle. Blood samples and 10 Visual Analog Scales (VAS) were collected before and after each condition. Participants were also asked after exercise: 'Did you experience a Runner's high'. Blood samples were analysed for endocannabinoids: N-arachidonoylethanolamine (AEA; anandamide), 2-arachidonoylglycerol (2-AG) and 1-arachidonoylglycerol (1-AG), and endocannabinoid-like lipid mediators: palmitoylethanolamide (PEA), oleoylethanolamide (OEA) and stearoylethanolamide (SEA). Cancer patients had lower circulating AEA, OEA and log SEA versus controls across all timepoints (all p < 0.06). In the total cohort, exercise increased AEA, log 1-AG, OEA, PEA and log SEA (all p = 0.05) while log 2-AG did not change. Of 10 VAS, only Happiness increased with exercise in the total cohort (p = 0.02). There were no group x time effects or associations between ECS and VAS responses to exercise. Five patients per group (50%) reported experiencing a Runner's high. Exercise increased endocannabinoids and endocannabinoid-like lipid mediators in the total cohort. However, cancer patients exhibited lower AEA, OEA and SEA concentrations versus their peers, indicating potential ECS dysfunction. Additional research is required to investigate the effect of various modalities and dosages of exercise on ECS markers and the clinical interpretation of these adaptations across a range of cancer populations. Australian New Zealand Clinical Trials Registry #: ACTRN12623000193673.

Enzyme-responsive oleoylethanolamide-releasing nanomedicine for sustained liver delivery and therapeutic improvement in early-stage metabolic dysfunction-associated steatohepatitis (MASH).

Time-controlled online SPE: strategic approach for N-acylethanolamines quantification in complex matrices.

Targeting metabolic syndrome with ALIAmides: A novel multi-mechanistic approach.

N-Acylethanolamines in cancer: mechanisms and therapeutic potential of lipid regulators of tumor behavior.

Throughout human history, medicinal plants have always been used as medicine to treat various diseases, extracts and active compounds of the medicinal plant most use of the therapies and play a major role in medication since the beginning of human civilization and also contribute to the manufacturing of drugs these days. The purpose of this study was to assess the Justicia adhatoda L. butanol (JABE) and methanol (JAME) leaves extracts for potential against lipid peroxidation activity, as well as for several antioxidant assays. A number of characteristics were examined, such as anti-lipid peroxidation, scavenging of free radicals (ferric reducing power potential, iron chelating activity, hydroxyl, hydrogen peroxide, superoxide and nitric oxide radicals). The JABE and JAME extracts was also subjected to HR-LCMS analysis. The HR-LCMS analysis revealed the makeup of a variety of bioactive compounds, such as Andrographolide, Vasicinone, vincamine, Curcumin, Kaempferitrin, 6-Gingerol, Sitagliptin, Kynurenic acid, Oleoyl ethanolamide, Luotonin A and many more, which exhibit numerous pharmacological activities such as antioxidant, anti-inflammatory, anticancer, and antidiabetic, antihypertensive, antimicrobial, antiaging, hepatoprotective, lipid lowering potential. These fractions also demonstrated a strong correlation with the IC50 values for the scavenging of hydrogen peroxide radicals, superoxide radicals, anti-lipid peroxidation, nitric oxide, iron chelating and hydroxyl radical efficacy. Additionally, the maximum scavenging activity for the above mention assays and for the reduction of Fe3+ to Fe2+ was demonstrated by both the fractions. The current findings indicated that Justicia adhatoda L. leaves, specifically the JABE and JAME fractions, have therapeutic potential as agent to prevent damage caused by free radicals.

Fatty acid ethanolamides (FAEAs) are bioactive lipidsinvolvedin inflammation, pain modulation, and energy homeostasis, gaininginterest in the pharmaceutical, nutraceutical, and cosmetic sectors.Here, we present an intensified biocatalytic strategy for the synthesisof a mixture of FAEAspalmitoylethanolamide (PEA), oleoylethanolamide(OLA), stearoylethanolamide (SEA), and linoleoylethanolamide (LEA)startingfrom microbial lipids extracted fromCutaneotrichosporonoleaginosus, cultivated on whey permeate, a majordairy byproduct, supplemented with waste cooking oil. The two-stepenzymatic cascadetransesterification of triacylglycerols intoethyl esters followed by aminolysis with ethanolaminewas catalyzedby Novozym 435 (immobilized Candida antarctica lipaseB) in green solvents. Whereas ethanol has been used for the firststep, eucalyptol proved particularly effective in aminolysis reactionwith >99% conversion and complete selectivity. Process intensification via a SpinChem rotating bed reactor led to a 5-fold reductionin reaction time (48 to 10 h), a 5- to 7-times increase in space-timeyield and quantitative yields for both steps. Biocatalyst reusabilityand process reproducibility was preserved. This integrated platformexemplifies a circular bioeconomy approach by valorizing agri-industrialresidues into high-value compounds through clean and scalable technologies.The resulting FAEAs hold potential for synergistic therapeutic applications,while supporting cost-effective and sustainable manufacturing acrossdiverse industries.

Previous research has demonstrated that the transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) effectively models early brain inflammation resulting from sudden hypoperfusion and subsequent reperfusion. According to studies showing that diet and nutrition strongly influence brain neuroplasticity, in this study we evaluated whether kaempferol (KAM), a dietary flavonoid, offers neuroprotection in a rat BCCAO/R model. Adult Wistar rats were gavage fed a single dose of KAM (40 mg) six hours before surgery. Comprehensive lipidomic and molecular analyses were conducted on samples from the frontal and temporal-occipital cortices, as well as the plasma. In the frontal cortex, KAM elevated anti-inflammatory N-acylethanolamines palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHAEA) and reduced oxidized arachidonic acid metabolites. KAM also downregulated cyclooxygenase- 2 (COX-2) protein and selectively decreased the endocannabinoid 2-arachidonoylglycerol (2-AG), showing a shift in AA metabolism. These molecular changes correlated with increased levels of peroxisome proliferator-activated receptor alpha (PPARα) and cannabinoid receptors CB1R and CB2R, supporting activation of both nuclear and membrane-bound anti-inflammatory pathways. No significant changes were observed in the temporal-occipital cortex. In plasma, DHAEA levels increased similarly to those in the cortex. However, rises in PEA and OEA were detected only in sham-operated KAM-treated animals, suggesting possible central redistribution under hypoperfusion/reperfusion stress. In summary, these findings demonstrate that KAM exerts dual anti-inflammatory effects by inhibiting COX-2-mediated prostanoid synthesis and promoting PPARα-driven lipid signaling. This dual mechanism highlights the potential of KAM as a dietary intervention to reduce neuroinflammation associated with hypoperfusion–reperfusion challenges.

The endocannabinoid system regulates immune function, inflammation, and metabolism and has gained increasing attention in clinical research. However, the instability, low abundance, and physicochemical complexity of endocannabinoids (ECs) and EC-like substances (EC-like) make their quantification in plasma analytically challenging. The authors developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of N-arachidonoylethanolamide (AEA), 2-arachidonoylglycerol, and its isomer 1-arachidonoylglycerol (2-AG/1-AG), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA) in human plasma. Extraction was performed using liquid-liquid extraction combined with liquid chromatography-tandem mass spectrometry. The method achieved lower limits of quantification of 0.1 mcg/L for AEA, 0.2 mcg/L for 2-AG/1-AG, and 0.5 mcg/L for OEA and PEA, with calibration curves showing high linearity (R2 ≥ 0.995). Intra-assay and interassay accuracy and precision were both within 15%. Additional validation parameters, including selectivity, recovery, carryover, matrix suitability, and dilution integrity, fulfilled regulatory criteria. Preanalytical handling significantly influenced concentrations: Delayed centrifugation and postthaw storage increased AEA, OEA, and PEA levels. The validated method was applied to plasma samples from patients coinfected with HIV and hepatitis C virus, enabling reproducible quantification of ECs and EC-like substances in a clinically relevant cohort. The study demonstrates that biological and technical factors markedly affect plasma EC and EC-like concentrations. Standardized preanalytical processing is therefore essential for accurate measurement, and the proposed method provides a robust tool for clinical and pharmacological research.

Sex differences in endocannabinoid and inflammatory markers associated with posttraumatic stress disorder.

Endocannabinoid and steroid hormone levels during and after pregnancy in fingernail samples from mothers and their infants.

This systematic review and meta-analysis of randomized controlled trials study sought to assess the effects of oleoylethanolamide (OEA) supplementation on many parameters related to cardiometabolic disorders. A thorough search was conducted across major databases using specific keywords to identify randomized controlled trials assessing the impact of OEA on cardiometabolic variables. The weighted mean difference (WMD) and 95% confidence intervals were calculated with a random-effects model. Data from 13 studies indicated substantial reductions in fasting blood sugar (WMD: -5.84 mg/dl), insulin (WMD: -3.26 µU/ml), waist circumference (WMD: -2.15 cm), triglycerides (WMD: -17.73 mg/dl), tumor necrosis factor-alpha (WMD: -2.44 pg/ml), and interleukin 6 (WMD: -0.87 pg/ml). An elevation in total antioxidant capacity (WMD: 0.43 mg/dl) was seen subsequent to OEA treatment. No substantial impacts were seen on other parameters. OEA supplementation, among other lifestyle variables, seems to provide significant improvements in certain cardiometabolic and oxidative stress-related indicators.

Anti-obesity effects of Oleoylethanolamide: Modulation of mitochondrial bioenergetics, endocannabinoidome and gut microbiome.

Oleoylethanolamide-producing Lactobacillus paracasei F19 improves metabolic and behavioral disorders by restoring intestinal permeability and microbiota-gut-brain axis in high-fat diet-induced obese male mice.

The endocannabinoid and paracannabinoid systems in natural reward processes: possible pharmacological targets?

Oleoylethanolamide (OEA) is a naturally occurring lipid that has been studied for its potential role in weight management and metabolic health. Through comprehensive meta-analysis, we aim to clarify the potential benefits of OEA in improving inflammation, oxidative stress, and metabolic parameters. To identify relevant randomized controlled trials (RCTs), a comprehensive search was conducted using Google Scholar and four databases: PubMed, Embase, Scopus, and Web of Science, up to November 2024. Eligible trials were detected by screening, and related data were extracted, respectively. Pooled effect sizes were calculated using meta-analyses and expressed as standard mean difference (SMD) with a 95% confidence interval (CI). Ten trials (with 11 treatment arms) were eligible for inclusion in this review. Meta-analysis revealed that OEA supplementation led to a significant improvement in C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), total antioxidant capacity (TAC), malondialdehyde (MDA), body weight, body mass index (BMI), waist circumference (WC), fat mass (FM), body fat percentage (BFP), triglycerides (TG), fasting blood glucose (FBG), insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) levels. However, no significant changes were observed in interleukin 6 (IL-6), fat-free mass (FFM), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and hemoglobin A1C (HbA1c) following OEA intake. Supplementation with OEA may help improve glycemic control, weight loss, waist circumference, fat mass, fat percentage, inflammation, and oxidative stress. However, further research is needed to establish definitive conclusions regarding its efficacy and long-term benefits.

Intermittent fasting (IF), Time-Restricted Intermittent Fasting (TRIF), and fasting-mimicking diets have gained popularity among weight loss programs. The body efficiently utilizes its energy reserves to activate metabolic processes in response to food intake. Modifying food regimens can alter/extend life span and promote healthy aging by activating specific metabolic processes. However, changes in general lipid metabolism, especially the alteration in N-acylethanolamide (NAE) regulation and their role in promoting lipolysis and extending life span during TRIF, are still inadequately explored. To bridge the knowledge gap, this study focuses on enhancing Oleoylethanolamine (OEA), a precursor molecule that instigates satiety, promotes lipolysis and extends the life span of model system, Caenorhabditis elegans. TRIF regimen in C. elegans induces OEA, which in turn lead to satiety followed by lipolysis and ATP synthesis. Lipolysis is stimulated by the increase in Adipose Tissue Triglyceride Lipase-1 (ATGL-1) activity that results from the enrichment in OEA precursor. In addition, the TRIF regimen induces oxidative stress resistance in C. elegans. Subsequently, this promotes longevity and slow aging in C. elegans by altering the insulin/ insulin-like growth factor signaling (IIS) pathway. The present study suggested the beneficial effects of time-restricted fasting in the eukaryotic model nematodes through the activation of lipid metabolism that involves enhanced production of OEA precursors which promotes lipolysis. In addition, the data revealed that the increased ATP production resulted in oxidative stress tolerance that promoted longevity and slow aging processes.

Oleoylethanolamide ameliorates collagen-induced rheumatoid arthritis via activation of GPR119.