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Viruses Jun 2023Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to...
Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need. Since gut fermentation of fiber produces short-chain fatty acids (SCFA) with antiviral potential, developing a fatty acid-based broad-spectrum antiviral was investigated. Molecular docking of fatty acids showed α-linolenic acid (ALA) is likely to interact with CoV-2-S, NL63-CoV-S, and RSV-F, and an ALA-containing liposome interacted with CoV-2 directly, degrading the particle. Furthermore, a combination of ALA and a SCFA-acetate synergistically inhibited CoV2-N expression and significantly reduced viral plaque formation and IL-6 and IL-1β transcript expression in Calu-3 cells, while increasing the expression of IFN-β. A similar effect was also observed in RSV-infected A549 cells. Moreover, mice infected with a murine-adapted SARS-CoV-2 (MA10) and treated with an ALA-liposome encapsulating acetate showed significant reductions in plaque-forming units present in lung tissue and in infection-associated lung inflammation and cytokines. Taken together, these results demonstrate that the ALA liposome-encapsulating acetate can be a promising broad antiviral therapy against respiratory infections.
Topics: Animals; Mice; SARS-CoV-2; Liposomes; alpha-Linolenic Acid; Molecular Docking Simulation; COVID-19; Respiratory Syncytial Virus Infections; Antiviral Agents; Respiratory Syncytial Virus, Human; Acetates
PubMed: 37515117
DOI: 10.3390/v15071429 -
Progress in Lipid Research Oct 2016Alpha-linolenic acid (ALA) is an essential fatty acid and the substrate for the synthesis of longer-chain, more unsaturated ω-3 fatty acids, eicosapentaenoic acid... (Review)
Review
Alpha-linolenic acid (ALA) is an essential fatty acid and the substrate for the synthesis of longer-chain, more unsaturated ω-3 fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA). EPA and DHA are associated with human health benefits. The primary source of EPA and DHA is seafood. There is a need for sustainable sources of biologically active ω-3 fatty acids. Certain plants contain high concentrations of ALA and stearidonic acid (SDA). Here we review the literature on the metabolism of ALA and SDA in humans, the impact of increased ALA and SDA consumption on concentrations of EPA and DHA in blood and cell lipid pools, and the extent to which ALA and SDA might have health benefits. Although it is generally considered that humans have limited capacity for conversion of ALA to EPA and DHA, sex differences in conversion to DHA have been identified. If conversion of ALA to EPA and DHA is limited, then ALA may have a smaller health benefit than EPA and DHA. SDA is more readily converted to EPA and appears to offer better potential for health improvement than ALA. However, conversion of both ALA and SDA to DHA is limited in most humans.
Topics: Diet; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids, Omega-3; Humans; Plants; alpha-Linolenic Acid
PubMed: 27496755
DOI: 10.1016/j.plipres.2016.07.002 -
International Journal of Biological... Jan 2021Alzheimer's disease is characterized by important patho-proteins, which being composed of Amyloid-β plaques and intracellular neurofibrillary tangles of Tau....
Alzheimer's disease is characterized by important patho-proteins, which being composed of Amyloid-β plaques and intracellular neurofibrillary tangles of Tau. Intrinsically disordered protein tau has several interacting partners, which are necessary for its normal functioning. Tau has been shown to interact with various proteins, nucleic acid, and lipids. α-Linolenic acid (ALA) a plant-based omega-3 fatty acid has been studied for its role as neuroprotective and beneficial fatty acid in the brain. In this study, we are focusing on the ability of ALA to induce spontaneous assembly in tau protein. ALA inhibited the Tau aggregation as indicated by reduced ThS fluorescence kinetics, which indicates no aggregation of Tau. Similarly, SDS-PAGE analysis supported that ALA exposure inhibited the aggregation as no higher-order tau species were observed. Along with its ability to impede the aggregation of Tau, ALA also maintains a native random coiled structure, which was estimated by CD spectroscopy. Finally, TEM analysis showed that the formation of Tau fibrils was found to be discouraged by ALA. Hence, conclusion of the study suggested that ALA profoundly inhibited aggregation of Tau and maintained it's the random-coil structure.
Topics: Humans; Protein Conformation; Protein Multimerization; Protein Unfolding; alpha-Linolenic Acid; tau Proteins
PubMed: 33130263
DOI: 10.1016/j.ijbiomac.2020.10.226 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia,... (Meta-Analysis)
Meta-Analysis Review
Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.
Topics: Adult; Humans; Cardiovascular Diseases; alpha-Linolenic Acid; Overweight; Randomized Controlled Trials as Topic; Cholesterol, HDL; Obesity; Dietary Supplements
PubMed: 37778442
DOI: 10.1016/j.advnut.2023.09.010 -
International Journal of Nanomedicine 2021Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility....
PURPOSE
Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo.
METHODS
We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated.
RESULTS
The size of ALA-PTX NPs was approximately 110.7±1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5-2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models.
CONCLUSION
ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.
Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Endocytosis; Mice; Nanoparticles; Paclitaxel; alpha-Linolenic Acid
PubMed: 34737564
DOI: 10.2147/IJN.S331578 -
Acta Biomaterialia Mar 2022Polyunsaturated fatty acids (PUFAs) play an important role in the establishment and the maintenance of the skin barrier function. However, the impact of their derived...
Polyunsaturated fatty acids (PUFAs) play an important role in the establishment and the maintenance of the skin barrier function. However, the impact of their derived lipid mediators remains unclear. Skin substitutes were engineered according to the self-assembly method with a culture medium supplemented with 10 μM of both α-linolenic acid (ALA) and linoleic acid (LA). The supplementation with ALA and LA decreased testosterone absorption through a tissue-engineered reconstructed skin model, thus indicating an improved skin barrier function following supplementation. The exogenously provided fatty acids were incorporated into the phospholipid and triglyceride fractions of the skin substitutes. Indeed, the dual supplementation increased the levels of eicosapentaenoic acid (EPA) (15-fold), docosapentaenoic acid (DPA) (3-fold), and LA (1.5-fold) in the epidermal phospholipids while it increased the levels of ALA (>20-fold), DPA (3-fold) and LA (1.5-fold) in the epidermal triglycerides. The bioactive lipid mediator profile of the skin substitutes, including prostaglandins, hydroxy-fatty acids, N-acylethanolamines and monoacylglycerols, was next analyzed using liquid chromatography-tandem mass spectrometry. The lipid supplementation further modulated bioactive lipid mediator levels of the reconstructed skin substitutes, leading to a lipid mediator profile more representative of the one found in normal human skin. These findings show that an optimized supply of PUFAs via culture media is essential for the establishment of improved barrier function in vitro. STATEMENT OF SIGNIFICANCE: Supplementation of the culture medium with 10 μM of both α-linolenic acid (ALA) and linoleic acid (LA) improved the skin barrier function of a tissue-engineered skin model. The exogenously provided fatty acids were incorporated into the phospholipid and triglyceride fractions of the skin substitutes and further modulated bioactive lipid mediator levels, including prostaglandins, hydroxy-fatty acids, N-acylethanolamines and monoacylglycerols. These findings highlight the important role of ALA and LA in skin homeostasis and show that an optimized supply of polyunsaturated fatty acids via culture media is essential for the establishment of improved barrier function in vitro.
Topics: Eicosapentaenoic Acid; Humans; Linoleic Acid; Lipidomics; Skin; alpha-Linolenic Acid
PubMed: 34808417
DOI: 10.1016/j.actbio.2021.11.021 -
Molecules (Basel, Switzerland) Oct 2022Gas chromatography (GC) with flame ionization detection (FID) and mass spectrometry (MS) detection were used to characterize the fatty acid (FA) compositions of ten...
Gas chromatography (GC) with flame ionization detection (FID) and mass spectrometry (MS) detection were used to characterize the fatty acid (FA) compositions of ten commonly consumed (i.e., market class) pulses. Lipids from ground pulses were extracted using a classical chloroform/methanol extraction and quantified by GC-FID with structural confirmation by GC-MS. Principal component analysis (PCA) was applied to FA compositions of the pulse extracts, and the pulses clustered into three distinct groups: one rich in linolenic acid, 18:3 (carbon number:unsaturation, C:U), one rich in 16:0, and one in which 18:1 was highest, along with predominant 18:2. These ten pulses averaged 46.1% linoleic acid (18:2), 22.7% oleic acid (18:1), 18.0% palmitic acid (16:0), and 7.6% linolenic acid (18:3). Individual values ranged widely, with 18:2 ranging from 26.0% in black beans to 48.4% in garbanzo beans. The greatest difference was in 18:3, which ranged from 2.2% in garbanzo beans to 38.8% in pinto beans. Oxo-FA were observed in all ten samples, and the distribution of oxo-FA in the samples also varied. Overall, the very different FA compositions of pulses lead to the possibility of breeding and genetic modification between pulses to produce the most desirable FA composition for nutritional benefit.
Topics: Fatty Acids; Gas Chromatography-Mass Spectrometry; alpha-Linolenic Acid; Plant Breeding; Flame Ionization; Fabaceae
PubMed: 36364086
DOI: 10.3390/molecules27217260 -
Pediatric Research May 2022Intrauterine hyperglycemia can harm a fetus's growth and development, and this can be seen in the umbilical cord blood metabolism disorder. However, the metabolites and...
BACKGROUND
Intrauterine hyperglycemia can harm a fetus's growth and development, and this can be seen in the umbilical cord blood metabolism disorder. However, the metabolites and metabolic mechanisms involved in the condition remain unknown.
METHODS
Targeted metabolomics using liquid chromatography and MetaboAnalyst were conducted in this study to explore differences in metabolites and metabolic pathways between individuals with hyperglycemia or well-controlled gestational diabetes mellitus (GDM) and healthy controls.
RESULTS
Univariate analysis found that the hyperglycemic and healthy control groups differed in 30 metabolites, while the well-controlled GDM and the healthy control groups differed only in three metabolites-ursodeoxycholic acid, docosahexaenoic acid, and 8,11,14-eicosatrienoic acid. Most of these metabolic variations were negatively associated with neonatal weights. Further research showed that the variations in the metabolites were primarily associated with the metabolic pathways of linoleic acid (LA) and alpha-linolenic acid (ALA).
CONCLUSION
Gestational hyperglycemia and well-controlled GDM, which may play a major role by inhibiting the LA and ALA metabolic pathways, have detrimental effects on cord blood metabolism.
IMPACT
The main point of this paper is that intrauterine hyperglycemia has a negative effect on cord blood metabolism mainly through the linoleic acid and alpha-linolenic acid metabolic pathways. This is a study to report a new association between well-controlled GDM and cord blood metabolism. This study provides a possible explanation for the association between intrauterine hyperglycemia and neonatal adverse birth outcomes.
Topics: Diabetes, Gestational; Female; Fetal Blood; Humans; Hyperglycemia; Infant, Newborn; Linoleic Acid; Metabolomics; Pregnancy; alpha-Linolenic Acid
PubMed: 33980991
DOI: 10.1038/s41390-021-01516-4 -
The Journal of Biological Chemistry Jul 2023Sustainable TGF-β1 signaling drives organ fibrogenesis. However, the cellular adaptation to maintain TGF-β1 signaling remains unclear. In this study, we revealed that...
Sustainable TGF-β1 signaling drives organ fibrogenesis. However, the cellular adaptation to maintain TGF-β1 signaling remains unclear. In this study, we revealed that dietary folate restriction promoted the resolution of liver fibrosis in mice with nonalcoholic steatohepatitis. In activated hepatic stellate cells, folate shifted toward mitochondrial metabolism to sustain TGF-β1 signaling. Mechanistically, nontargeted metabolomics screening identified that α-linolenic acid (ALA) is exhausted by mitochondrial folate metabolism in activated hepatic stellate cells. Knocking down serine hydroxymethyltransferase 2 increases the bioconversion of ALA to docosahexaenoic acid, which inhibits TGF-β1 signaling. Finally, blocking mitochondrial folate metabolism promoted liver fibrosis resolution in nonalcoholic steatohepatitis mice. In conclusion, mitochondrial folate metabolism/ALA exhaustion/TGF-βR1 reproduction is a feedforward signaling to sustain profibrotic TGF-β1 signaling, and targeting mitochondrial folate metabolism is a promising strategy to enforce liver fibrosis resolution.
Topics: Animals; Mice; alpha-Linolenic Acid; Hepatic Stellate Cells; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Transforming Growth Factor beta1; Folic Acid; Mitochondria; Folic Acid Deficiency; Signal Transduction; Feedback, Physiological
PubMed: 37307917
DOI: 10.1016/j.jbc.2023.104909 -
Journal of Animal Science Jan 2024Both n-6 and n-3 fatty acids (FA) have numerous significant physiological roles for mammals. The interplay between these families of FA is of interest in companion... (Review)
Review
Both n-6 and n-3 fatty acids (FA) have numerous significant physiological roles for mammals. The interplay between these families of FA is of interest in companion animal nutrition due to the influence of the n-6:n-3 FA ratio on the modulation of the inflammatory response in disease management and treatment. As both human and animal diets have shifted to greater consumption of vegetable oils rich in n-6 FA, the supplementation of n-3 FA to canine, feline, and equine diets has been advocated for. Although fish oils are commonly added to supply the long-chain n-3 FA eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), a heavy reliance on this ingredient by the human, pet food, and equine supplement industries is not environmentally sustainable. Instead, sustainable sourcing of plant-based oils rich in n-3 α-linolenic acid (ALA), such as flaxseed and camelina oils, emerges as a viable option to support an optimal n-6:n-3 FA ratio. Moreover, ALA may offer health benefits that extend beyond its role as a precursor for endogenous EPA and DHA production. The following review underlines the metabolism and recommendations of n-6 and n-3 FA for dogs, cats, and horses and the ratio between them in promoting optimal health and inflammation management. Additionally, insights into both marine and plant-based n-3 FA sources will be discussed, along with the commercial practicality of using plant oils rich in ALA for the provision of n-3 FA to companion animals.
Topics: Animals; Dogs; Horses; Cats; Fatty Acids, Omega-3; alpha-Linolenic Acid; Fatty Acids, Omega-6; Animal Feed; Diet; Animal Nutritional Physiological Phenomena
PubMed: 38776363
DOI: 10.1093/jas/skae143