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Antioxidants (Basel, Switzerland) Sep 2023is a poorly understood plant in the context of biological activity, despite its widespread application in ethnomedicine in numerous European countries. The aim of this...
is a poorly understood plant in the context of biological activity, despite its widespread application in ethnomedicine in numerous European countries. The aim of this study was to assess the cytotoxic potential of the plant against human colorectal adenocarcinoma (HT29) and to isolate the plant components linked to this effect. Ultra-high performance liquid chromatography with a high-resolution/quadrupole time-of-flight mass spectrometer (UHPLC-HR/QTOF/MS-PDA) was used for the phytochemical characterization of the extract. Liquid-liquid extraction and preparative chromatography were employed for fractionation purposes. Our investigation demonstrated that the ethyl acetate fraction from showed significant cytotoxicity, and a bioactivity-guided approach led to the isolation of oxylipins, including traumatic acid, pinellic acid, and 9,10-dihydroxy-8-oxsooctadec-12-enic acid. The structures of the compounds were confirmed by nuclear magnetic resonance spectroscopy. Among these compounds, the last one exhibited significant cytotoxicity, though without selectivity, and traumatic acid was characterized by mild cytotoxicity. The cytotoxicity was linked to intracellular reactive oxygen species generation.
PubMed: 37760007
DOI: 10.3390/antiox12091704 -
F1000Research 2023Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by autoantibody production and synovial membrane damage. It significantly impairs overall... (Randomized Controlled Trial)
Randomized Controlled Trial
Role of specialized pro-resolving mediators on inflammation, cardiometabolic health, disease progression, and quality of life after omega-3 PUFA supplementation and aerobic exercise training in individuals with rheumatoid arthritis: a randomized 16-week, placebo-controlled interventional trial.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by autoantibody production and synovial membrane damage. It significantly impairs overall function and quality of life. Consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and regular aerobic exercise (AEx) training are reported to have positive effects on the progression of RA. However, the mechanisms behind these benefits are still inconclusive. This study protocol will investigate the effects of n-3 PUFA supplementation and AEx training on disease progression, cardiometabolic health, and quality of life, and their association with the plasma and synovial fluid levels of specialized pro-resolving mediators (SPMs) in subjects with RA. The study consists of a 16-week intervention period, during which participants will be randomly assigned in a double-blinded manner to one of four groups: placebo control (PLA), PLA+AEx, n-3, or n-3+AEx. The PLA groups will be given a gelatin-filled capsule, while the n-3 groups will be given n-3 PUFAs equivalent to 2.5 g/d of docosahexaenoic acid and 0.5 g/d of eicosapentaenoic acid. The AEx groups will perform exercise three times per week on a stationary electronically braked cycle ergometer at 60-70% of their VO2peak for 50-60 minutes. Before and after the intervention, participants will undergo RA-specific and functional measurements, peak aerobic capacity test, and a dietary and physical activity assessment. Venous blood and synovial fluid from the knee joint will be collected. Changes in disease progression, cardiometabolic health, and quality of life, as well as erythrocyte membrane composition to assess n-3 incorporation, SPM levels, inflammatory markers, and gene expression from blood and synovial fluid will be analyzed. The study aims to elucidate the SPMs that regulate the inflammatory gene expression pathways and associate them with the improvements in disease progression, cardiometabolic health, and quality of life after n-3 PUFA supplementation and AEx training. : ClinicalTrials.gov #NCT05945693.
Topics: Humans; Arthritis, Rheumatoid; Fatty Acids, Omega-3; Quality of Life; Dietary Supplements; Disease Progression; Exercise; Inflammation; Double-Blind Method; Male; Female; Middle Aged; Adult
PubMed: 38778807
DOI: 10.12688/f1000research.138392.1 -
Annals of Nutrition & Metabolism 2024Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype effect of iron metabolism disorders, we investigated the...
Eicosanoids and Oxylipin Signature in Hereditary Hemochromatosis Patients Are Similar to Dysmetabolic Iron Overload Syndrome Patients but Are Impacted by Dietary Iron Absorption.
INTRODUCTION
Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype effect of iron metabolism disorders, we investigated the oxylipin profile in hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) patients.
METHODS
An LC-MS/MS-based method was performed to quantify plasma oxylipins in 20 HH and 20 DIOS patients in fasting conditions and 3 h after an iron-rich meal in HH patients.
RESULTS
Principal component analysis showed no separation between HH and DIOS, suggesting that the clinical phenotype has no direct impact on oxylipin metabolism. 20-HETE was higher in DIOS and correlated with hypertension (p = 0.03). Different oxylipin signatures were observed in HH before and after the iron-rich meal. Discriminant oxylipins include epoxy fatty acids derived from docosahexaenoic acid and arachidonic acid as well as 13-HODE and 9-HODE. Mediation analysis found no major contribution of dietary iron absorption for 16/22 oxylipins significantly affected by the meal.
DISCUSSION
The oxylipin profiles of HH and DIOS seemed similar except for 20-HETE, possibly reflecting different hypertension prevalence between the two groups. Oxylipins were significantly affected by the iron-rich meal, but the specific contribution of iron was not clear. Although iron may contribute to oxidative stress and inflammation in HH and DIOS, this does not seem to directly affect oxylipin metabolism.
Topics: Humans; Oxylipins; Male; Female; Hemochromatosis; Middle Aged; Iron, Dietary; Adult; Eicosanoids; Iron Overload; Hydroxyeicosatetraenoic Acids; Tandem Mass Spectrometry; Oxidative Stress; Principal Component Analysis; Aged; Linoleic Acids; Chromatography, Liquid
PubMed: 38354712
DOI: 10.1159/000536657 -
Arthritis Research & Therapy Feb 2024Rheumatoid arthritis (RA) is typically preceded by an extended preclinical period where circulating autoantibodies, particularly anti-citrullinated protein antibodies...
BACKGROUND
Rheumatoid arthritis (RA) is typically preceded by an extended preclinical period where circulating autoantibodies, particularly anti-citrullinated protein antibodies (ACPA), are detectable in the absence of clinical arthritis. Increased dietary intake of anti-inflammatory omega-3 (ω3) polyunsaturated fatty acids (PUFA) has been shown to be associated with a lower the risk of developing incident RA in large epidemiological studies. It is currently not known how changes in fatty acid (FA) metabolism may impact on the progression towards RA in at-risk individuals. To begin to address this question, we profiled serum FAs and oxylipins in an established cohort of at-risk ACPA-positive first-degree relatives (FDR) of RA patients (N = 31), some of whom developed RA (N = 4), and compared their profile to ACPA-negative FDR from the same population (N = 10).
METHODS
Gas chromatography (GC) was used for FA quantitation. Oxylipins were extracted and quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS).
RESULTS
Although we did not detect any meaningful differences in overall FA content between ACPA + and ACPA - FDR, the levels of oxylipins derived from FA metabolism demonstrated significant differences between the two groups, with the ACPA + group demonstrating enrichment in circulating arachidonic acid- and eicosapentaenoic acid-derived molecules. Compared with the ACPA - FDR group, the ACPA + FDR, including those who progressed into inflammatory arthritis, displayed higher levels of LOX-derived oxylipins.
CONCLUSION
ACPA seropositivity in otherwise unaffected individuals at-risk for developing future RA based on family history (FDR) is associated with alterations in the serum oxylipin profile that suggests dysregulated LOX activity.
Topics: Humans; Anti-Citrullinated Protein Antibodies; Oxylipins; Tandem Mass Spectrometry; Arthritis, Rheumatoid; Autoantibodies; Lipoxygenases
PubMed: 38360827
DOI: 10.1186/s13075-024-03274-0 -
Journal of Pharmaceutical and... Jun 2024Oxylipins are important low abundant signaling molecules in living organisms. In platelets they play a primary role in platelet activation and aggregation in the course...
Non-enantioselective, enantioselective, and two-dimensional liquid chromatography coupled with tandem mass spectrometry for the study of stereochemical disposition of oxylipins in cGMP-regulated hemin-treated platelets.
Oxylipins are important low abundant signaling molecules in living organisms. In platelets they play a primary role in platelet activation and aggregation in the course of thrombotic events. In vivo, they are enzymatically synthesized by cyclooxygenases, lipoxygenases, or cytochrome P450 isoenzmes, resulting in diverse polyunsaturated fatty acid (FA) metabolites including hydroxy-, epoxy-, oxo-FAs, and endoperoxides with pro-thrombotic or anti-thrombotic effects. In a recent study, it was reported that hemin induces platelet death which was accompanied by enhanced reactive oxygen species (ROS) production (measured by flow cytometry) and lipid peroxidation (as determined by proxy using flow cytometry with BODIPY-C11 as sensor). Lipidomic studies further indicated significant changes of the platelet lipidome upon ex vivo hemin treatment, amongst others oxylipins were increased. The effect could be (at least partly) reversed by riociguat/diethylamine NONOate diethylammonium salt (DEA/NO) which modulates the soluble guanylate cyclase(sGC)-cGMP-cGMP-dependent protein kinase I(cGKI) signaling axis. In the original work, oxylipins were measured by a non-enantioselective UHPLC-tandem-MS assay which may not give the full picture whether oxylipin elevation is due to ROS or by enzymatic processes. We present here the study of the stereochemical disposition of hemin-induced platelet lipidome alterations using Chiralpak IA-U column with amylose tris(3,5-dimethylphenylcarbamate) chiral selector immobilized on 1.6 µm silica particles. It was found that the major platelet oxylipins 12-HETE, 12-HEPE and 14-HDoHE (from 12-LOX) and 12-HHT (from COX-1) were present in S-configuration indicating their enzymatic formation. On the other hand, both R and S enantiomers of 9- and 13-HODE, 11- and 15-HETE were detected, possibly due to enzyme promiscuity rather than non-specific oxidation (by ROS or autoxidation), as confirmed by multi-loop based two-dimensional LC-MS using selective comprehensive mode with achiral RPLC in the 1st dimension and chiral LC in the 2nd using a multiple heart-cutting interface. For 12-HETrE, a peak at the retention time of the R-enantiomer was ruled out as isobaric interference by 2D-LC-MS. In particular, arachidonic acid derivates 12(S)-HHT, 11(R)-HETE and 15(S)-HETE were found to be sensitive to hemin and cGMP modulation.
PubMed: 38943819
DOI: 10.1016/j.jpba.2024.116328 -
International Journal of Molecular... Sep 2023Stressed organisms identify intracellular molecules released from damaged cells due to trauma or pathogen infection as components of the innate immune response. These...
Stressed organisms identify intracellular molecules released from damaged cells due to trauma or pathogen infection as components of the innate immune response. These molecules called DAMPs (Damage-Associated Molecular Patterns) are extracellular ATP, sugars, and extracellular DNA, among others. Animals and plants can recognize their own DNA applied externally (self-exDNA) as a DAMP with a high degree of specificity. However, little is known about the microalgae responses to damage when exposed to DAMPs and specifically to self-exDNAs. Here we compared the response of the oilseed microalgae to self-exDNA, with the stress responses elicited by nonself-exDNA, methyl jasmonate (MeJA) and sodium bicarbonate (NaHCO). We analyzed the peroxidase enzyme activity related to the production of reactive oxygen species (ROS), as well as the production of polyphenols, lipids, triacylglycerols, and phytohormones. After 5 min of addition, self-exDNA induced peroxidase enzyme activity higher than the other elicitors. Polyphenols and lipids were increased by self-exDNA at 48 and 24 h, respectively. Triacylglycerols were increased with all elicitors from addition and up to 48 h, except with nonself-exDNA. Regarding phytohormones, self-exDNA and MeJA increased gibberellic acid, isopentenyladenine, and benzylaminopurine at 24 h. Results show that have self-exDNA specific responses.
Topics: Animals; Microalgae; Plant Growth Regulators; Peroxidase; Alarmins; Chlorophyceae; Coloring Agents; DNA; Oxylipins; Peroxidases
PubMed: 37762475
DOI: 10.3390/ijms241814172 -
BMC Plant Biology Apr 2024Mango (Mangifera indica L.) is grown in Hainan, Guangdong, Yunnan, Sichuan, and Fujian provinces and Guanxi autonomous region of China. However, trees growing in these...
BACKGROUND
Mango (Mangifera indica L.) is grown in Hainan, Guangdong, Yunnan, Sichuan, and Fujian provinces and Guanxi autonomous region of China. However, trees growing in these areas suffer severe cold stress during winter, which affects the yield. To this regard, data on global metabolome and transcriptome profiles of leaves are limited. Here, we used combined metabolome and transcriptome analyses of leaves of three mango cultivars with different cold stress tolerance, i.e. Jinhuang (J)-tolerant, Tainung (T) and Guiremang No. 82 (G)-susceptible, after 24 (LF), 48 (MF) and 72 (HF) hours of cold.
RESULTS
A total of 1,323 metabolites belonging to 12 compound classes were detected. Of these, amino acids and derivatives, nucleotides and derivatives, and lipids accumulated in higher quantities after cold stress exposure in the three cultivars. Notably, Jinhuang leaves showed increasing accumulation trends of flavonoids, terpenoids, lignans and coumarins, and alkaloids with exposure time. Among the phytohormones, jasmonic acid and abscisic acid levels decreased, while N6-isopentenyladenine increased with cold stress time. Transcriptome analysis led to the identification of 22,526 differentially expressed genes. Many genes enriched in photosynthesis, antenna proteins, flavonoid, terpenoid (di- and sesquiterpenoids) and alkaloid biosynthesis pathways were upregulated in Jihuang leaves. Moreover, expression changes related to phytohormones, MAPK (including calcium and HO), and the ICE-CBF-COR signalling cascade indicate involvement of these pathways in cold stress responses.
CONCLUSION
Cold stress tolerance in mango leaves is associated with regulation of primary and secondary metabolite biosynthesis pathways. Jasmonic acid, abscisic acid, and cytokinins are potential regulators of cold stress responses in mango leaves.
Topics: Transcriptome; Cold-Shock Response; Mangifera; Plant Growth Regulators; Abscisic Acid; Hydrogen Peroxide; China; Gene Expression Profiling; Gene Expression Regulation, Plant; Cyclopentanes; Oxylipins
PubMed: 38600447
DOI: 10.1186/s12870-024-04983-z -
Scientific Reports May 2024Fatty acids are precursors of inflammatory oxylipins. In the context of COVID-19, an excessive production of pro-inflammatory cytokines is associated with disease...
Fatty acids are precursors of inflammatory oxylipins. In the context of COVID-19, an excessive production of pro-inflammatory cytokines is associated with disease severity. The objective was to investigate whether the baseline omega 3/omega 6 fatty acids ratio and the oxylipins were associated with inflammation and oxidative stress in unvaccinated patients with COVID-19, classified according to the severity of the disease during hospitalization. This Prospective population-based cohort study included 180 hospitalized patients with COVID-19. The patients were classified into five groups according to the severity of their disease. Group 1 was the least severe and Group 5 was the most severe. Three specific types of fatty acids-eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)-as well as their enzymatic and non-enzymatic oxylipins were determined using chromatography coupled mass spectrometry. There was no difference in the ratio of omega-3 to omega-6 fatty acids between the groups (p = 0.276). However, the EPA/AA ratio was lower in Group 4 compared to Group 1 (p = 0.015). This finding was associated with an increase in both C-Reactive Protein (p < 0.001) and Interleukin-6 (p = 0.002). Furthermore, the concentration of F-Isoprostanes was higher in Group 4 than in Group 1 (p = 0.009), while no significant changes were observed for other oxylipins among groups. Multivariate analysis did not present any standard of biomarkers, suggesting the high complexity of factors involved in the disease severity. Our hypothesis was confirmed in terms of EPA/AA ratio. A higher EPA/AA ratio upon hospital admission was found to be associated with lower concentration of C-Reactive Protein and Interleukin-6, leading to a better prognosis of hospitalized SARS-CoV-2 patients. Importantly, this beneficial outcome was achieved without any form of supplementation. The trial also provides important information that can be further applied to reduce the severity of infections associated with an uncontrolled synthesis of pro-inflammatory cytokines.Trial registration: https://clinicaltrials.gov/study/NCT04449718 -01/06/2020. ClinicalTrials.gov Identifier: NCT04449718.
Topics: Humans; COVID-19; Male; Female; Middle Aged; Fatty Acids, Omega-3; Aged; Severity of Illness Index; Prospective Studies; Hospitalization; SARS-CoV-2; Oxylipins; Eicosapentaenoic Acid; Oxidative Stress; Docosahexaenoic Acids; Adult; Inflammation
PubMed: 38702342
DOI: 10.1038/s41598-024-60815-y -
Frontiers in Immunology 2023Phagocytosis of inhaled crystalline silica (cSiO) particles by tissue-resident alveolar macrophages (AMs) initiates generation of proinflammatory eicosanoids derived...
INTRODUCTION
Phagocytosis of inhaled crystalline silica (cSiO) particles by tissue-resident alveolar macrophages (AMs) initiates generation of proinflammatory eicosanoids derived from the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (ARA) that contribute to chronic inflammatory disease in the lung. While supplementation with the ω-3 PUFA docosahexaenoic acid (DHA) may influence injurious cSiO-triggered oxylipin responses, investigation of this hypothesis in physiologically relevant AMs is challenging due to their short-lived nature and low recovery numbers from mouse lungs. To overcome these challenges, we employed fetal liver-derived alveolar-like macrophages (FLAMs), a self-renewing surrogate that is phenotypically representative of primary lung AMs, to discern how DHA influences cSiO-induced eicosanoids.
METHODS
We first compared how delivery of 25 µM DHA as ethanolic suspensions or as bovine serum albumin (BSA) complexes to C57BL/6 FLAMs impacts phospholipid fatty acid content. We subsequently treated FLAMs with 25 µM ethanolic DHA or ethanol vehicle (VEH) for 24 h, with or without LPS priming for 2 h, and with or without cSiO for 1.5 or 4 h and then measured oxylipin production by LC-MS lipidomics targeting for 156 oxylipins. Results were further related to concurrent proinflammatory cytokine production and cell death induction.
RESULTS
DHA delivery as ethanolic suspensions or BSA complexes were similarly effective at increasing ω-3 PUFA content of phospholipids while decreasing the ω-6 PUFA arachidonic acid (ARA) and the ω-9 monounsaturated fatty acid oleic acid. cSiO time-dependently elicited myriad ARA-derived eicosanoids consisting of prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acids in unprimed and LPS-primed FLAMs. This cSiO-induced eicosanoid storm was dramatically suppressed in DHA-supplemented FLAMs which instead produced potentially pro-resolving DHA-derived docosanoids. cSiO elicited marked IL-1α, IL-1β, and TNF-α release after 1.5 and 4 h of cSiO exposure in LPS-primed FLAMs which was significantly inhibited by DHA. DHA did not affect cSiO-triggered death induction in unprimed FLAMs but modestly enhanced it in LPS-primed FLAMs.
DISCUSSION
FLAMs are amenable to lipidome modulation by DHA which suppresses cSiO-triggered production of ARA-derived eicosanoids and proinflammatory cytokines. FLAMs are a potential alternative to primary AMs for investigating interventions against early toxicant-triggered inflammation in the lung.
Topics: Mice; Animals; Docosahexaenoic Acids; Oxylipins; Macrophages, Alveolar; Lipopolysaccharides; Silicon Dioxide; Mice, Inbred C57BL; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Arachidonic Acid; Dietary Supplements
PubMed: 38022527
DOI: 10.3389/fimmu.2023.1274147 -
Genes Aug 2023Foliage-feeding fall armyworm (FAW; ) and root-feeding western corn rootworm (WCR; ) are maize ( L.) pests that cause significant yield losses. Jasmonic acid (JA) plays...
Foliage-feeding fall armyworm (FAW; ) and root-feeding western corn rootworm (WCR; ) are maize ( L.) pests that cause significant yield losses. Jasmonic acid (JA) plays a pivotal defense role against insects. 12-oxo-phytodienoic acid (12-OPDA) is converted into JA by peroxisome-localized OPDA reductases (OPR). However, little is known about the physiological functions of cytoplasmic OPRs. Here, we show that disruption of reduced wound-induced JA production and defense against FAW while accumulating more JA catabolites. Overexpression of in enhanced JA production and defense against beet armyworm (BAW; ). In addition, double mutants were more susceptible than either single mutant, suggesting that and uniquely and additively contributed to defense. In contrast to the defensive roles of and in leaves, single mutants did not display any alteration in root herbivory defense against WCR. Feeding on double mutants resulted in increased WCR mortality associated with greater herbivory-induced production of insecticidal death acids and ketols. Thus, and cooperatively inhibit the synthesis of these metabolites during herbivory by WCR. We conclude that and regulate JA-mediated resistance in leaves against FAW while suppressing insecticidal oxylipin synthesis in roots during WCR infestation.
PubMed: 37761872
DOI: 10.3390/genes14091732