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Cell Adhesion & Migration Dec 2021Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer's disease (AD). The extracellular burden of amyloid-β plaques...
Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer's disease (AD). The extracellular burden of amyloid-β plaques and Tau seed fabricate the activation of microglia. The seeding effect of extracellular Tau species is an emerging aspect to study about Tauopathies in AD. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. The excessive neuroinflammation cumulatively hampers phagocytic function of microglia reducing the clearance of extracellular protein aggregates. Omega-3 fatty acids, especially docosahexaenoic acid and eicosapentaenoic acid, are recognized to induce anti-inflammatory phenotype of microglia. In addition to increased cytokine production, omega-3 fatty acids enhance phagocytic receptors expression in microglia. In this study, we have observed the phagocytosis of extracellular Tau in the presence of α-linolenic acid (ALA). The increased phagocytosis of extracellular Tau monomer and aggregates have been observed upon ALA exposure to microglia cells. After internalization, the degradation status of Tau has been studied with early and late endosomal markers Rab5 and Rab7. Further, the lysosome-mediated degradation of internalized Tau was studied with LAMP-2A, a lysosome marker. The enhanced migratory ability in the presence of ALA could be beneficial for microglia to access the target and clear it. The increased migration of microglia was found to induce the microtubule-organizing center repolarization. The data indicate that the dietary fatty acids ALA could significantly enhance phagocytosis and intracellular degradation of internalized Tau. Our results suggest that microglia could be influenced to reduce extracellular Tau seed with dietary fatty acids.
Topics: Alzheimer Disease; Humans; Microglia; Neuroinflammatory Diseases; Phagocytosis; alpha-Linolenic Acid; tau Proteins
PubMed: 33724164
DOI: 10.1080/19336918.2021.1898727 -
Food & Function Feb 2023Sarcopenia is a syndrome of age-related loss of muscle mass and strength that seriously affects human health, and there are currently no effective drugs to treat the...
Sarcopenia is a syndrome of age-related loss of muscle mass and strength that seriously affects human health, and there are currently no effective drugs to treat the disease. Linolenic acid as a common n-3 polyunsaturated fatty acid (n-3 PUFA) is known to have many beneficial functions. Some studies have found that n-3 PUFA might have the potential to improve sarcopenia. In this study, () was used as a model animal to investigate the effects of linolenic acid on muscles. The results showed that 50 μg mL linolenic acid significantly improved sarcopenia by repairing mitochondrial function by promoting mitophagy and fighting oxidative stress ( < 0.05). This included the increase of the expression of the mitophagy gene and DAF-16/FOXO transcription factors, respectively, by linolenic acid. This study could provide some evidence for the application of n-3 PUFA in improving sarcopenia.
Topics: Animals; Humans; Caenorhabditis elegans; Sarcopenia; alpha-Linolenic Acid; Caenorhabditis elegans Proteins; Mitophagy; Oxidative Stress; Fatty Acids, Omega-3; Forkhead Transcription Factors; Longevity
PubMed: 36651495
DOI: 10.1039/d2fo02974j -
American Journal of Reproductive... Oct 2021This study aims to investigate the effects of alpha-linolenic acid (ALA) on the gut microbiota (GM) and the abdominal environment in mice with endometriosis (EMS).
PROBLEM
This study aims to investigate the effects of alpha-linolenic acid (ALA) on the gut microbiota (GM) and the abdominal environment in mice with endometriosis (EMS).
METHODS
The effects of faecal microbiota transplantation (FMT) from EMS mice on mice treated with antibiotic cocktail were conducted. The 16S rRNA sequencing and PICRUSt software were used to detect the structure and function of GM respectively. The protein levels of Claudin 4 and ZO-2 in the intestinal wall were detected using the western blotting. The level of LPS in the abdominal cavity was detected using enzyme-linked immunosorbent assay (ELISA). The content of macrophages in the abdominal cavity was detected using flow cytometry.
RESULTS
The exogenous supplementation of ALA could restore the abundance of Firmicutes and Bacteroidota in EMS mice. After the ALA treatment, the abundance of 125 functional pathways and 50 abnormal enzymes related to GM in EMS mice was significantly improved (p < .05). The expression of the ZO-2 protein in the intestinal wall was decreased, and the level of LPS in the abdominal cavity was significantly increased after FMT from EMS mice (p < .05). ALA could increase the expression of the ZO-2 protein in the intestinal wall of EMS mice, reduce the level of LPS in the abdominal cavity (p < .05) and reduce the aggregation of peritoneal macrophages (p < .05).
CONCLUSION
Alpha-linolenic acid can improve the GM, intestinal wall barrier and abdominal inflammatory environment and reduce the level of LPS in mice with EMS.
Topics: Animals; Disease Models, Animal; Endometriosis; Female; Gastrointestinal Microbiome; Mice; Zonula Occludens-2 Protein; alpha-Linolenic Acid
PubMed: 34022075
DOI: 10.1111/aji.13471 -
Journal of Drug Targeting Feb 2023Dissolving microneedles, the promising vehicles for transdermal delivery, are incapable of directly loading hydrophobic components that limit the application of...
Dissolving microneedles, the promising vehicles for transdermal delivery, are incapable of directly loading hydrophobic components that limit the application of transdermal drug delivery. Microemulsion holds great potential in the solubilisation of water-insoluble drugs but is limited by the high epidermal retention. In this study, we fabricated microemulsion-incorporated dissolving microneedles co-loading celecoxib and α-linolenic acid (Cel-MEs@MNs) for enhancing osteoarthritis (OA) therapy synergistic anti-inflammation and potent transdermal delivery. Cel-MEs@MNs composed of celecoxib & α-linolenic acid-coloaded microemulsion (Cel-MEs) and hyaluronic acid-based microneedles (MNs) can be completely dissolved in 90 s with a particle size of ∼30 nm. Each microneedle array with a hardness exceeding 30 N contained 57.9 ± 2.5 μg of celecoxib and 442.5 ± 24.2 μg of α-linolenic acid. The 8 h-cumulative transdermal of celecoxib from Cel-MEs@MNs was 89.2 ± 5.1 μg celecoxib/cm, which is 2.98-fold higher than that from Cel-MEs. Combinational celecoxib and α-linolenic acid with a weight ratio of 1/5 can synergistically induce M1-like macrophage to M2 repolarization, reduce M1-like macrophages-resulted chondrocytes apoptosis, and lower serum prostaglandin E-2 (PGE-2). Notably, Cel-MEs@MNs amplified such collaborated anti-inflammatory effects. More importantly, in the treatment of OA-bearing rat models, Cel-MEs@MNs with a half-dose of celecoxib and α-linolenic acid significantly shrunk the paw swelling, reduced inflammatory cytokines, and improved cartilage damage compared with the oral administration of celecoxib and α-linolenic acid, as well as transdermal administration of Cel-MEs. Such an integrational strategy of microemulsion-incorporated dissolving MNs offers the feasibility of combinational celecoxib and α-linolenic acid in transdermal permeation and boosted OA therapy.
Topics: Rats; Animals; Administration, Cutaneous; Celecoxib; alpha-Linolenic Acid; Drug Delivery Systems; Osteoarthritis; Needles
PubMed: 36093744
DOI: 10.1080/1061186X.2022.2123492 -
Molecules (Basel, Switzerland) Jan 2022Water shortage caused by long-term drought is one of the most serious abiotic stress factors in maize. Different drought conditions lead to differences in growth,...
Water shortage caused by long-term drought is one of the most serious abiotic stress factors in maize. Different drought conditions lead to differences in growth, development, and metabolism of maize. In previous studies, proteomics and genomics methods have been widely used to explain the response mechanism of maize to long-term drought, but there are only a few articles related to metabolomics. In this study, we used transcriptome and metabolomics analysis to characterize the differential effects of drought stress imposed at seedling or flowering stages on maize. Through the association analysis of genes and metabolites, we found that maize leaves had 61 and 54 enriched pathways under seedling drought and flowering drought, respectively, of which 13 and 11 were significant key pathways, mostly related to the biosynthesis of flavonoids and phenylpropanes, glutathione metabolism and purine metabolism. Interestingly, we found that the α-linolenic acid metabolic pathway differed significantly between the two treatments, and a total of 10 differentially expressed genes and five differentially abundant metabolites have been identified in this pathway. Some differential accumulation of metabolites (DAMs) was related to synthesis of jasmonic acid, which may be one of the key pathways underpinning maize response to different types of long-term drought. In general, metabolomics provides a new method for the study of water stress in maize and lays a theoretical foundation for drought-resistant cultivation of silage maize.
Topics: Droughts; Flowers; Gene Expression Regulation, Plant; Genes, Plant; Metabolomics; Seedlings; Stress, Physiological; Zea mays; alpha-Linolenic Acid
PubMed: 35164035
DOI: 10.3390/molecules27030771 -
Life Sciences Jan 2024Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia... (Review)
Review
Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia accompanied by memory loss and depression. The direct pathways and specific mechanisms in the central nervous system (CNS) for addressing fatty acid imbalances in MetS have not yet been fully elucidated. Among polyunsaturated acids, linoleic acid (LA, n6-PUFA) and α-linolenic acid (ALA, n3-PUFA), which are two essential fatty acids that should be provided by food sources (e.g., vegetable oils and seeds), have been reported to regulate various cellular mechanisms including apoptosis, inflammatory responses, mitochondrial biogenesis, and insulin signaling. Furthermore, inadequate intake of LA and ALA is reported to be involved in neuropathology and neuropsychiatric diseases as well as imbalanced metabolic conditions. Herein, we review the roles of LA and ALA on metabolic-related dementia focusing on insulin resistance, dyslipidemia, synaptic plasticity, cognitive function, and neuropsychiatric issues. This review suggests that LA and ALA are important fatty acids for concurrent treatment of both MetS and neurological problems.
Topics: Humans; Linoleic Acid; alpha-Linolenic Acid; Insulin Resistance; Fatty Acids; Cognitive Dysfunction; Dyslipidemias; Dementia
PubMed: 38123015
DOI: 10.1016/j.lfs.2023.122356 -
International Journal of Biological... Feb 2017In this study, we report the protective effects of linolenic acid towards the formation of early (HbAc) and advanced glycation end-products (AGEs) based on fluorescence,...
In this study, we report the protective effects of linolenic acid towards the formation of early (HbAc) and advanced glycation end-products (AGEs) based on fluorescence, circular dichroism, confocal microscopy and molecular interaction studies. Linolenic acid was found to be a potent inhibitor of AGEs formed by both glucose and fructose. The HbAc (early glycation product) level was found to be reduced to 7.4% when compared to glycated control (8.4%). Similarly, linolenic acid also inhibited the methylglyoxal mediated AGEs formation. Circular dichroism spectroscopy studies suggested that the protective effect of linolenic acid for the helical structure of albumin. The molecular interaction studies showed that linolenic acid interacts with arginine residues of albumin with high affinity. Results suggested linolenic acid to be a potent antiglycation compound and also it could be a better lead compound for AGE inhibition.
Topics: Animals; Cattle; Glycation End Products, Advanced; Glycosylation; Molecular Docking Simulation; Protein Aggregates; Protein Binding; Protein Conformation; Protein Stability; Serum Albumin, Bovine; alpha-Linolenic Acid
PubMed: 27845223
DOI: 10.1016/j.ijbiomac.2016.11.035 -
International Journal of Molecular... Jul 2023A reduced risk of obesity and metabolic syndrome has been observed in individuals with a low intake ratio of linoleic acid/α-linolenic acid (LA/ALA). However, the...
A reduced risk of obesity and metabolic syndrome has been observed in individuals with a low intake ratio of linoleic acid/α-linolenic acid (LA/ALA). However, the influence of a low ratio of LA/ALA intake on lipid metabolism and endogenous fatty acid distribution in obese patients remains elusive. In this investigation, 8-week-old C57BL/6J mice were randomly assigned to four groups: low-fat diet (LFD) as a control, high-fat diet (HFD), high-fat diet with a low LA/ALA ratio (HFD+H3L6), and high-fat diet with a high LA/ALA ratio (HFD+L3H6) for 16 weeks. Our results show that the HFD+H3L6 diet significantly decreased the liver index of HFD mice by 3.51%, as well as the levels of triacylglycerols (TGs) and low-density lipoprotein cholesterol (LDL-C) by 15.67% and 10.02%, respectively. Moreover, the HFD+H3L6 diet reduced the pro-inflammatory cytokines interleukin-6 (IL-6) level and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and elevated the level of superoxide dismutase (SOD) in the liver. The HFD+H3L6 diet also resulted in the downregulation of fatty acid synthetase () and sterol regulatory element binding proteins-1c () expression and the upregulation of peroxisome proliferator-activated receptor-α () and acyl-CoA oxidase 1 () gene expression in the liver. The low LA/ALA ratio diet led to a notable increase in the levels of ALA and its downstream derivative docosahexaenoic acid (DHA) in the erythrocyte, liver, perienteric fat, epididymal fat, perirenal fat, spleen, brain, heart, and gastrocnemius, with a strong positive correlation. Conversely, the accumulation of LA in abdominal fat was more prominent, and a high LA/ALA ratio diet exacerbated the deposition effect of LA. In conclusion, the low LA/ALA ratio not only regulated endogenous fatty acid levels but also upregulated and and downregulated and gene expression levels, thus maintaining lipid homeostasis. Optimizing dietary fat intake is important in studying lipid nutrition. These research findings emphasize the significance of understanding and optimizing dietary fat intake.
Topics: Mice; Animals; Fatty Acids; Lipid Metabolism; alpha-Linolenic Acid; Linoleic Acid; Mice, Obese; Peroxisome Proliferator-Activated Receptors; Sterol Regulatory Element Binding Protein 1; Mice, Inbred C57BL; Liver; Diet, High-Fat; Obesity
PubMed: 37569494
DOI: 10.3390/ijms241512117 -
Brazilian Journal of Biology = Revista... 2021The objective of the current study was to investigate the synergistic impact of α-Tocopherol and α-Linolenic acid (100 µM) on IVM and IVC of Nili Ravi buffalo...
The objective of the current study was to investigate the synergistic impact of α-Tocopherol and α-Linolenic acid (100 µM) on IVM and IVC of Nili Ravi buffalo oocytes. Oocytes were obtained from the ovaries of slaughtered buffaloes within two hours after slaughter and brought to laboratory. Buffalo cumulus oocyte complexes were placed randomly in the five experimental groups included; GROUP 1: Maturation media (MM) + 100 µM ALA (control), GROUP 2: MM + 100 µM ALA + 50μM α-Tocopherol, GROUP 3: MM + 100 µM ALA + 100μM α-Tocopherol, GROUP 4: MM + 100 µM ALA + 200 μM α-Tocopherol and GROUP 5: MM + 100 µM ALA + 300 μM α-Tocopherol under an atmosphere of 5% CO2 in air at 38.5 °C for 22-24 h. Cumulus expansion and nuclear maturation status was determined (Experiment 1). In experiment 2, oocytes were matured as in experiment 1. The matured oocytes were then fertilized in Tyrode's Albumin Lactate Pyruvate (TALP) medium for about 20 h and cultured in synthetic oviductal fluid (SOF) medium to determine effect of α-Linolenic acid (100 µM) and α-Tocopherol in IVM medium on IVC of presumptive zygotes. To study the effect of α-Linolenic acid (100 µM) in IVM media and increasing concentration of α-tocopherol in the culture media on early embryo development (Experiment 3), the presumptive zygotes were randomly distributed into the five experimental groups with increasing concentration of α-tocopherol in culture media. Higher percentage of MII stage oocytes in experiment 1(65.2±2.0), embryos at morula stage in experiment 2 (30.4±1.5) and experiment 3 (22.2±2.0) were obtained. However, overall results for cumulus cell expansion, maturation of oocyte to MII stage and subsequent embryo development among treatments remain statistically similar (P > 0.05). Supplementation of α-tocopherol in maturation media having α-Linolenic acid and/or in embryo culture media did not further enhance in vitro maturation of oocyte or embryo production.
Topics: Animals; Buffaloes; Culture Media; Embryonic Development; Oocytes; alpha-Linolenic Acid; alpha-Tocopherol
PubMed: 34932678
DOI: 10.1590/1519-6984.253514 -
International Journal of Molecular... Aug 2018Jasmonic acid (JA) and its related derivatives are ubiquitously occurring compounds of land plants acting in numerous stress responses and development. Recent studies... (Review)
Review
Jasmonic acid (JA) and its related derivatives are ubiquitously occurring compounds of land plants acting in numerous stress responses and development. Recent studies on evolution of JA and other oxylipins indicated conserved biosynthesis. JA formation is initiated by oxygenation of α-linolenic acid (α-LeA, 18:3) or 16:3 fatty acid of chloroplast membranes leading to 12-oxo-phytodienoic acid (OPDA) as intermediate compound, but in and , OPDA and some of its derivatives are final products active in a conserved signaling pathway. JA formation and its metabolic conversion take place in chloroplasts, peroxisomes and cytosol, respectively. Metabolites of JA are formed in 12 different pathways leading to active, inactive and partially active compounds. The isoleucine conjugate of JA (JA-Ile) is the ligand of the receptor component COI1 in vascular plants, whereas in the bryophyte COI1 perceives an OPDA derivative indicating its functionally conserved activity. JA-induced gene expressions in the numerous biotic and abiotic stress responses and development are initiated in a well-studied complex regulation by homeostasis of transcription factors functioning as repressors and activators.
Topics: Bryopsida; Chloroplasts; Cyclopentanes; Fatty Acids; Fatty Acids, Unsaturated; Marchantia; Metabolic Networks and Pathways; Oxylipins; Peroxisomes; Species Specificity; alpha-Linolenic Acid
PubMed: 30150593
DOI: 10.3390/ijms19092539