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Phytomedicine : International Journal... Apr 2023Nervonic acid (C24:1, 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fatty acid, plays an essential role in prevention of metabolic diseases,...
BACKGROUND
Nervonic acid (C24:1, 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fatty acid, plays an essential role in prevention of metabolic diseases, and immune regulation, and has anti-inflammatory properties. As a chronic, immune-mediated inflammatory disease, ulcerative colitis (UC) can affect the large intestine. The influences of NA on UC are largely unknown.
PURPOSE
The present study aimed to decipher the anti-UC effect of NA in the mouse colitis model. Specifically, we wanted to explore whether NA can regulate the levels of inflammatory factors in RAW264.7 cells and mouse colitis model.
METHODS
To address the above issues, the RAW264.7 cell inflammation model was established by lipopolysaccharide (LPS), then the inflammatory factors tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Interleukin-10 (IL-10) were detected by Enzyme-linked immunosorbent assay (ELISA). The therapeutic effects of NA for UC were evaluated using C57BL/6 mice gavaged dextran sodium sulfate (DSS). Hematoxylin and eosin (H&E) staining, Myeloperoxidase (MPO) kit assay, ELISA, immunofluorescence assay, and LC-MS/MS were used to assess histological changes, MPO levels, inflammatory factors release, expression and distribution of intestinal tight junction (TJ) protein ZO-1, and metabolic pathways, respectively. The levels of proteins involved in the nuclear factor kappa-B (NF-κB) pathway in the UC were investigated by western blotting and RT-qPCR.
RESULTS
In vitro experiments verified that NA could reduce inflammatory response and inhibit the activation of key signal pathways associated with inflammation in LPS-induced RAW264.7 cells. Further, results from the mouse colitis model suggested that NA could restore intestinal barrier function and suppress NF-κB signal pathways to ameliorate DSS-induced colitis. In addition, untargeted metabolomics analysis of NA protection against UC found that NA protected mice from colitis by regulating citrate cycle, amino acid metabolism, pyrimidine and purine metabolism.
CONCLUSION
These results suggested that NA could ameliorate the secretion of inflammatory factors, suppress the NF-κB signaling pathway, and protect the integrity of colon tissue, thereby having a novel role in prevention or treatment therapy for UC. This work for the first time indicated that NA might be a potential functional food ingredient for preventing and treating inflammatory bowel disease (IBD).
Topics: Animals; Mice; Chromatography, Liquid; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Acids, Monounsaturated; Inflammation; Lipopolysaccharides; Mice, Inbred C57BL; NF-kappa B; Signal Transduction; Tandem Mass Spectrometry
PubMed: 36764096
DOI: 10.1016/j.phymed.2023.154702 -
Clinical and Translational Medicine Jun 2022Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung...
Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer.
BACKGROUND
Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation.
METHODS
We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography-mass spectrometry (LC-MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC-MS-based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice.
RESULTS
Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all-trans-retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL-8 and NF-κB pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all-trans-retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri-treated Lewis lung cancer (LLC).
CONCLUSIONS
Overall, these results pointed out that P. copri-nervonic acid/all-trans-retinoic acid axis may contribute to the pathogenesis of NSCLC.
Topics: Animals; Bacteria; Carcinoma, Non-Small-Cell Lung; Humans; Inflammation; Lung Neoplasms; Metabolome; Mice; Mice, Inbred C57BL; Microbiota; Proteome; Tretinoin
PubMed: 35735103
DOI: 10.1002/ctm2.947 -
Journal of Oleo Science Oct 2023Nervonic acid (NA) is a very-long-chain monounsaturated fatty acid with great application values. It plays a vital role in the development of brain nervous system and...
Nervonic acid (NA) is a very-long-chain monounsaturated fatty acid with great application values. It plays a vital role in the development of brain nervous system and the treatment of neurological diseases, so it has attracted much attention from all walks of life. Although NA has a wide range of sources, its current acquisition methods are still mainly relied on chemical synthesis and plant extraction, which are challenging to meet the market and green industry demands, limiting its development and application. In recent years, with the rapid development of synthetic biology technology, NA biosynthesis has become an alternative production strategy. In this study, we summarize the physicochemical properties, pharmacological activities, resources, biosynthetic pathways and heterologous biosynthesis of NA, and discuss the challenges and prospects of NA biosynthesis. The application prospects of cell-free systems and retrobiosynthesis in NA synthesis were also reviewed.
PubMed: 37704446
DOI: 10.5650/jos.ess23039 -
Neurotherapeutics : the Journal of the... Apr 2022Adrenoleukodystrophy (ALD) is an X-linked inherited peroxisomal disorder due to mutations in the ALD protein and characterized by accumulation of very long-chain fatty...
Adrenoleukodystrophy (ALD) is an X-linked inherited peroxisomal disorder due to mutations in the ALD protein and characterized by accumulation of very long-chain fatty acids (VLCFA), specifically hexacosanoic acid (C26:0). This can trigger other pathological processes such as mitochondrial dysfunction, oxidative stress, and inflammation, which if involves the brain tissues can result in a lethal form of the disease called childhood cerebral ALD. With the recent addition of ALD to the Recommended Uniform Screening Panel, there is an increase in the number of individuals who are identified with ALD. However, currently, there is no approved treatment for pre-symptomatic individuals that can arrest or delay symptom development. Here, we report our observations investigating nervonic acid, a monounsaturated fatty acid as a potential therapy for ALD. Using ALD patient-derived fibroblasts, we examined whether nervonic acid can reverse VLCFA accumulation similar to erucic acid, the active ingredient in Lorenzo's oil, a dietary intervention believed to alter disease course. We have shown that nervonic acid can reverse total lipid C26:0 accumulation in a concentration-dependent manner in ALD cell lines. Further, we show that nervonic acid can protect ALD fibroblasts from oxidative insults, presumably by increasing intracellular ATP production. Thus, nervonic acid can be a potential therapeutic for individuals with ALD, which can alter cellular biochemistry and improve its function.
Topics: Adrenoleukodystrophy; Child; Fatty Acids; Fatty Acids, Monounsaturated; Fibroblasts; Humans
PubMed: 35378685
DOI: 10.1007/s13311-022-01226-7 -
Bioresources and Bioprocessing Oct 2023Nervonic acid, a natural fatty acid compound and also a core component of nerve fibers and nerve cells, has been widely used to prevent and treat related diseases of the...
Nervonic acid, a natural fatty acid compound and also a core component of nerve fibers and nerve cells, has been widely used to prevent and treat related diseases of the brain nervous system. At present, fatty acids and their derivatives are mainly obtained by natural extraction or chemical synthesis which are limited by natural resources and production costs. In this study, the de novo synthetic pathway of nervonic acid was constructed in Yarrowia lipolytica by means of synthetic biology, and the yield of nervonic acid was further improved by metabolic engineering and fermentation optimization. Specially, heterologous elongases and desaturases derived from different organism were successfully expressed and evaluated for their potential for the production of nervonic acid in Y. lipolytica. Meanwhile, we overexpressed the genes involved in the lipid metabolism to increase the nervonic acid titer to 111.6 mg/L. In addition, the potential of adding oil as auxiliary carbon sources for nervonic acid production by the engineered Y. lipolytica was analyzed. The results indicated that supplementation with colleseed oil as an auxiliary carbon source can be beneficial for the nervonic acid productivity, which led to the highest concentration of 185.0 mg/L in this work. To summarize, this study describes that the Y. lipolytica can be used as a promising platform for the production of nervonic acid and other very long-chain fatty acids.
PubMed: 38647797
DOI: 10.1186/s40643-023-00689-6 -
Frontiers in Plant Science 2021Nervonic acid (NA) is a very-long-chain monounsaturated fatty acid that plays crucial roles in brain development and has attracted widespread research interest. The... (Review)
Review
Nervonic acid (NA) is a very-long-chain monounsaturated fatty acid that plays crucial roles in brain development and has attracted widespread research interest. The markets encouraged the development of a refined, NA-enriched plant oil as feedstocks for the needed further studies of NA biological functions to the end commercial application. Plant seed oils offer a renewable and environmentally friendly source of NA, but their industrial production is presently hindered by various factors. This review focuses on the NA biosynthesis and assembly, NA resources from plants, and the genetic engineering of NA biosynthesis in oil crops, discusses the factors that affect NA production in genetically engineered oil crops, and provides prospects for the application of NA and prospective trends in the engineering of NA. This review emphasizes the progress made toward various NA-related topics and explores the limitations and trends, thereby providing integrated and comprehensive insight into the nature of NA production mechanisms during genetic engineering. Furthermore, this report supports further work involving the manipulation of NA production through transgenic technologies and molecular breeding for the enhancement of crop nutritional quality or creation of plant biochemical factories to produce NA for use in nutraceutical, pharmaceutical, and chemical industries.
PubMed: 33747006
DOI: 10.3389/fpls.2021.626625 -
Brain and Behavior Apr 2021Our previous metabolomics study showed that the plasma nervonic acid levels were higher in patients with major depressive disorder (MDD) than those in healthy controls...
OBJECTIVE
Our previous metabolomics study showed that the plasma nervonic acid levels were higher in patients with major depressive disorder (MDD) than those in healthy controls and patients with bipolar disorder (BD). To examine whether the nervonic acid levels differ in the central nervous system, we investigated the levels in the cerebrospinal fluid (CSF) of patients with MDD, BD, and healthy controls.
METHODS
Nervonic acid levels in CSF were measured by gas chromatography time-of-flight mass spectrometry. The participants included 30 patients with MDD, 30 patients with BD, and 30 healthy controls.
RESULTS
In contrast to our previous study, no significant differences were found in the nervonic acid level in the CSF among the patients with MDD, BD, and the healthy controls. Though no significant state-dependent changes were found among the three groups, we did observe a significant negative correlation between the nervonic acid levels and depressive symptoms in the depressive state of patients with MDD and BD (r = -0.38, p = .046). Further, a significant positive correlation was found between the nervonic acid levels and manic symptoms in the manic state of patients with BD (r = 0.79, p = .031).
CONCLUSION
The nervonic acid levels in the CSF did not differ among the patients with MDD, BD, and the healthy controls; however, a significant negative correlation with depressive symptoms and a positive correlation with manic symptoms was observed. Thus, the nervonic acid levels in the CSF may be a candidate biomarker for mood symptoms.
Topics: Biomarkers; Depressive Disorder, Major; Fatty Acids, Monounsaturated; Humans; Pilot Projects
PubMed: 33599392
DOI: 10.1002/brb3.2075 -
Biomedicines Sep 2021is a nosocomial pathogen, and its biofilms are tolerant to desiccation, nutrient starvation, and antimicrobial treatment on biotic and abiotic surfaces, tissues, and...
is a nosocomial pathogen, and its biofilms are tolerant to desiccation, nutrient starvation, and antimicrobial treatment on biotic and abiotic surfaces, tissues, and medical devices. Biofilm formation by is triggered by a quorum sensing cascade, and we hypothesized that fatty acids might inhibit its biofilm formation by interfering with quorum sensing. Initially, we investigated the antibiofilm activities of 24 fatty acids against ATCC 17978 and two clinical isolates. Among these fatty acids, two unsaturated fatty acids, nervonic and oleic acid, at 20 μg/mL significantly inhibited biofilm formation without affecting its planktonic cell growth (MICs were >500 μg/mL) and markedly decreased the motility of but had no toxic effect on the nematode . Interestingly, molecular dynamic simulations showed that both fatty acids bind to the quorum sensing acyl homoserine lactone synthase (AbaI), and decent conformational stabilities of interactions between the fatty acids and AbaI were exhibited. Our results demonstrate that nervonic and oleic acid inhibit biofilm formation by strains and may be used as lead molecules for the control of persistent infections.
PubMed: 34572317
DOI: 10.3390/biomedicines9091133 -
Food Science & Nutrition Oct 2023Nervonic acid (NA) is a kind of ultra-long-chain monounsaturated fatty acid, which can repair nerve cell damage caused by oxidative stress. Alzheimer's disease (AD) is a...
Nervonic acid (NA) is a kind of ultra-long-chain monounsaturated fatty acid, which can repair nerve cell damage caused by oxidative stress. Alzheimer's disease (AD) is a nervous system disease and often accompanied by the decline of learning and memory capacity. In this study, the combined dose of D-galactose/AlCl was used to establish a mouse model of AD. Meanwhile, the mice were treated with different doses of NA (10.95 and 43.93 mg/kg). The results showed that NA delayed the decline of locomotion and learning ability caused by D-galactose/AlCl, increased the activity of total superoxide dismutase, catalase, glutathione peroxidase, and reduced the content of malondialdehyde in vivo. Besides, NA reduced the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), aspartate aminotransferase, alanine aminotransferase, increased the levels of 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, alleviated the cell morphology damage induced by D-galactose/AlCl in hippocampus and liver tissue. Furthermore, the intervention of NA upregulated the expression levels of PI3K, AKT, and mTOR genes and downregulated the expression levels of TNF-α, IL-6, and IL-1β genes. Therefore, we speculate the intervention of NA could be an effective way in improving cognitive impairment through the activation of PI3K signaling pathway. These results suggest that NA has the potential to be developed as antioxidant drug for the prevention and early therapy of AD.
PubMed: 37823115
DOI: 10.1002/fsn3.3533 -
Frontiers in Plant Science 2018HSO-3-1 is a potential producer of nervonic acid, which could be accumulated to 2-3% of dry cell weight. Improving the productivity of nervonic acid is critical to...
HSO-3-1 is a potential producer of nervonic acid, which could be accumulated to 2-3% of dry cell weight. Improving the productivity of nervonic acid is critical to promote the commercialization of this product. In this study, 1-naphthylacetic acid (NAA) and tea polyphenol (TP) were selected as bioactive additives to stimulate the growth of . Supplementing NAA in the early growth stage and TP in the middle and late growth stage led to improved lipid accumulation in . The cultures supplemented with TP at the late growth stage maintained higher photosynthetic efficiency than the control groups without TP. Furthermore, the intracellular reactive oxygen species (ROS) accumulations in supplemented with 500 mg/L of TP was 63% lower than the control group. A linear relationship (= 0.899) between the values of Fv/Fm and ROS accumulation was established. We hypothesize supplement of bioactive additives at different growth stage could promote the cell growth rate and nervonic acid productivity of by retrieving intracellular ROS level. Further analysis of photosynthetic system II (PSII) protein in cultured in presence of NAA and TP indicated the levels of D1 and D2 proteins, the core skeleton proteins of PSII, showed 33.3 and 25.6% higher than the control group. CP43 protein, a critical module in PSII repair cycle, decreased significantly. These implied that TP possesses the function of slowing down the damage of PSII by scavenging excess intracellular ROS.
PubMed: 29731762
DOI: 10.3389/fpls.2018.00506