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1.
Mol Omics ; 19(9): 726-734, 2023 Oct 30.
Article de Anglais | MEDLINE | ID: mdl-37466104

RÉSUMÉ

Parkinson's disease (PD) is a serious neurodegenerative disorder wherein changes in metabolites related to lipids, glutathione, and energy metabolism occur. Currently, metabolite changes in PD have been reported, yet their role in the prognosis of disease remains poorly understood. Functional metabolites can be used to diagnose diseases, especially PD, and can exert neuroprotective effects. This study used a PD animal model and a lipopolysaccharide (LPS)-mediated inflammatory response model (using the BV-2 mouse microglial cell line) to identify functional metabolites that can identify important metabolic disorders during PD, and comprehensively evaluated their profiles using a metabolomics-based approach. Our results showed that co-treatment with myristic acid and heptadecanoic acid downregulated the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α in BV-2 cells. Additionally, myristic acid and 10 µM heptadecanoic acid significantly inhibited the LPS-induced inflammatory response through the nuclear factor-κB pathway in BV-2 microglial cells, which provides a potential approach for PD treatment. Myristic acid and heptadecanoic acid were the active metabolites found by active metabolomics technology, but at present, there is no research report about their function for PD treatment, and our findings offer a novel research strategy for PD diagnosis and treatment.


Sujet(s)
Facteur de transcription NF-kappa B , Maladie de Parkinson , Souris , Animaux , Facteur de transcription NF-kappa B/métabolisme , Facteur de transcription NF-kappa B/pharmacologie , Lipopolysaccharides/métabolisme , Lipopolysaccharides/pharmacologie , Microglie/métabolisme , Acide myristique/pharmacologie , Acide myristique/métabolisme , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/métabolisme , Maladie de Parkinson/métabolisme
2.
Small ; 19(39): e2301751, 2023 09.
Article de Anglais | MEDLINE | ID: mdl-37259675

RÉSUMÉ

Sustained oral uncoupler 2,4-dinitrophenol (DNP) administration exerts prominent anti-obesity effects, but the adipose tissue off-target disadvantage leads to systemic adverse effects. A novel non-cardiotoxicity DNP delivery method using a biocompatible microneedles patch containing the amphiphilic tetradecanoic acid-DNP ester (TADNP) is described, which is synthesized via esterification on the phenolic hydroxyl of DNP. The TADNP is self-assembled as nanomicelles, which enhance the endocytosis rate of DNP by adipocytes and its permeation in isolated adipose tissues. The microenvironment of adipose tissues promotes the massive release of DNP and plasma and simulated gastrointestinal fluids. The microneedles-delivered TADNP nanomicelles (MN-TADNP) effectively deliver DNP in treated adipose tissues and reduce DNP content in off-target organs. Both oral and MN patch-delivered TADNP micelles effectively exert anti-obesity effects in a mouse model of high-fat diet-induced obesity; and noteworthily, MN-TADNP exhibit more satisfactory biosafety than oral administration. Here, a smart MN patch loaded with tetradecanoic acid-modified DNP is reported, which enhances its accumulation in adipose tissues and exerts an anti-obesity effect without causing any systemic toxicity.


Sujet(s)
2,4-Dinitro-phénol , Lipogenèse , Souris , Animaux , 2,4-Dinitro-phénol/pharmacologie , Acide myristique/pharmacologie , Esters/pharmacologie , Obésité/traitement médicamenteux , Adipocytes , Dinitrophénols/pharmacologie
3.
FEBS Open Bio ; 12(10): 1788-1796, 2022 10.
Article de Anglais | MEDLINE | ID: mdl-35856166

RÉSUMÉ

Effective amelioration of type II diabetes requires therapies that increase both glucose uptake activity per cell and skeletal muscle mass. Myristic acid (14:0) increases diacylglycerol kinase (DGK) δ protein levels and enhances glucose uptake in myotubes in a DGKδ-dependent manner. However, it is still unclear whether myristic acid treatment affects skeletal muscle mass. In this study, we found that myristic acid treatment increased the protein level of ß-tubulin, which constitutes microtubules and is closely related to muscle mass, in C2C12 myotubes but not in the proliferation stage in C2C12 myoblasts. However, lauric (12:0), palmitic (16:0) and oleic (18:1) acids failed to affect DGKδ and ß-tubulin protein levels in C2C12 myotubes. Moreover, knockdown of DGKδ by siRNA significantly inhibited the increased protein level of ß-tubulin in the presence of myristic acid, suggesting that the increase in ß-tubulin protein by myristic acid depends on DGKδ. These results indicate that myristic acid selectively affects ß-tubulin protein levels in C2C12 myotubes via DGKδ, suggesting that this fatty acid improves skeletal muscle mass in addition to increasing glucose uptake activity per cell.


Sujet(s)
Diabète de type 2 , Diacylglycérol kinase , Diabète de type 2/métabolisme , Diacylglycérol kinase/génétique , Diacylglycérol kinase/métabolisme , Diacylglycérol kinase/pharmacologie , Glucose/métabolisme , Humains , Fibres musculaires squelettiques/métabolisme , Acide myristique/pharmacologie , Petit ARN interférent/pharmacologie , Tubuline/pharmacologie
4.
Microb Biotechnol ; 15(2): 590-602, 2022 02.
Article de Anglais | MEDLINE | ID: mdl-34156757

RÉSUMÉ

Biofilms are communities of bacteria, fungi or yeasts that form on diverse biotic or abiotic surfaces, and play important roles in pathogenesis and drug resistance. A generic saw palmetto oil inhibited biofilm formation by Staphylococcus aureus, Escherichia coli O157:H7 and fungal Candida albicans without affecting their planktonic cell growth. Two main components of the oil, lauric acid and myristic acid, are responsible for this antibiofilm activity. Their antibiofilm activities were observed in dual-species biofilms as well as three-species biofilms of S. aureus, E. coli O157:H7 and C. albicans. Transcriptomic analysis showed that lauric acid and myristic acid repressed the expressions of haemolysin genes (hla and hld) in S. aureus, several biofilm-related genes (csgAB, fimH and flhD) in E. coli and hypha cell wall gene HWP1 in C. albicans, which supported biofilm inhibition. Also, saw palmetto oil, lauric acid and myristic acid reduced virulence of three microbes in a nematode infection model and exhibited minimal cytotoxicity. Furthermore, combinatorial treatment of fatty acids and antibiotics showed synergistic antibacterial efficacy against S. aureus and E. coli O157:H7. These results demonstrate that saw palmetto oil and its main fatty acids might be useful for controlling bacterial infections as well as multispecies biofilms.


Sujet(s)
Escherichia coli O157 , Staphylococcus aureus , Antibactériens/pharmacologie , Biofilms , Candida albicans , Acides lauriques/pharmacologie , Acide myristique/pharmacologie , Extraits de plantes , Serenoa
5.
Int J Mol Sci ; 22(24)2021 Dec 17.
Article de Anglais | MEDLINE | ID: mdl-34948362

RÉSUMÉ

ATP-binding cassette (ABC) transporters are conserved in all kingdoms of life, where they transport substrates against a concentration gradient across membranes. Some ABC transporters are known to cause multidrug resistances in humans and are able to transport chemotherapeutics across cellular membranes. Similarly, BmrA, the ABC transporter of Bacillus subtilis, is involved in excretion of certain antibiotics out of bacterial cells. Screening of extract libraries isolated from fungi revealed that the C14 fatty acid myristic acid has an inhibitory effect on the BmrA ATPase as well as the transport activity. Thus, a natural membrane constituent inhibits the BmrA activity, a finding with physiological consequences as to the activity and regulation of ABC transporter activities in biological membranes.


Sujet(s)
Transporteurs ABC/antagonistes et inhibiteurs , Bacillus subtilis/effets des médicaments et des substances chimiques , Protéines bactériennes/antagonistes et inhibiteurs , Acide myristique/pharmacologie , Transporteurs ABC/métabolisme , Adenosine triphosphatases/antagonistes et inhibiteurs , Adenosine triphosphatases/métabolisme , Bacillus subtilis/métabolisme , Protéines bactériennes/métabolisme , Découverte de médicament
6.
J Oleo Sci ; 70(9): 1239-1246, 2021 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-34373405

RÉSUMÉ

Fatty acids and their derivatives are interesting cosmetic ingredients because they show the selective antibacterial activity against Staphylococcus aureus (S. aureus). However, the antibacterial activity in mixed systems containing several active ingredients is unclear because previous studies focused antibacterial systems containing one kind of fatty acid. In the present study, the minimal inhibitory concentration (MIC) and the fractional inhibitory concentration (FIC) were evaluated for myristic acid/lauric acid, myristic acid/palmitoleic acid, and myristic acid/lactic acid mixed systems to show the effect of the coexisting components on the selective antibacterial activity of myristic acid. In the myristic acid/palmitoleic acid mixed system, the antibacterial activity against S. aureus was enhanced by additive effect, whereas the antibacterial activity was not observed against S. epidermidis. On the other hand, the myristic acid/lauric acid mixed system showed antibacterial activity against S. epidermidis: Lauric acid impaired the selectivity of antibacterial activity of myristic acid. These results suggest that the selective activity of myristic acid varies with the additives. The present findings are useful for designing formulations of cosmetics and body cleansers containing myristic acid.


Sujet(s)
Cosmétiques/composition chimique , Cosmétiques/pharmacologie , Acide myristique/pharmacologie , Staphylococcus aureus/effets des médicaments et des substances chimiques , Interactions médicamenteuses , Résistance bactérienne aux médicaments , Acides gras monoinsaturés/pharmacologie , Acides lauriques/pharmacologie , Staphylococcus epidermidis/effets des médicaments et des substances chimiques
7.
J Oleo Sci ; 70(6): 787-797, 2021 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-33967172

RÉSUMÉ

1,2-Alkanediols are characteristic cosmetic ingredients because these moisturizers exhibit the antibacterial activity against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). However, the antimicrobial behavior in mixed systems containing several active ingredients is unclear because previous reports focus on an antibacterial system containing only 1,2-alkanediol. In this study, the minimal inhibitory concentration (MIC) and the fractional inhibitory concentration (FIC) were evaluated for 1,2-dodecanediol/lactic acid, 1,2-dodecanediol/myristic acid, 1,2-dodecanediol/methylparaben, and 1,2-dodecanediol/isopropyl methylphenol mixed systems to show the effect of the addition of other antimicrobial components to 1,2-dodecanediol. The antibacterial property of 1,2-dodecanediol/lactic acid mixed system was almost similar compared to 1,2-dodecanediol monomeric system. On the other hand, the antimicrobial activity of 1,2-dodecanediol against S. epidermidis was inhibited in the 1,2-dodecanediol/myristic acid mixed system. Because the selective antimicrobial activity of myristic acid against S. aureus was demonstrated in the mixed system. The present findings are useful for designing formulations of cosmetics and body cleansers containing 1,2-dodecanediol.


Sujet(s)
Antibactériens/pharmacologie , Alcools gras/pharmacologie , Glycols/pharmacologie , Staphylococcus aureus/effets des médicaments et des substances chimiques , Staphylococcus epidermidis/effets des médicaments et des substances chimiques , Synergie des médicaments , Acide lactique/pharmacologie , Tests de sensibilité microbienne , Acide myristique/pharmacologie , Parabènes/pharmacologie , Phénols/pharmacologie
8.
Life Sci ; 278: 119605, 2021 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-33989665

RÉSUMÉ

Diabetes mellitus (DM) may lead to testicular-related infertility while Myristic acid (MA) is beneficial to lower hyperglycaemia. Thus, we hypothesized that MA could protect testes against hyperglycaemia-induced damage in DM. DM was induced in adult male rats by high-fat diet consumption for 12 weeks, accompanied by a single dose streptozotocin injection. Following DM confirmation, the rats were fed orally with 10 and 20 mg/kg body weight MA for 28 consecutive days. After completion of treatment, rats were sacrificed and blood, cauda epididymis and testes were harvested. Serum was separated, epididymal sperm was collected for analysis. Molecular studies of the testes were performed by qPCR, Western blotting and immunostaining. MA was found to protect the testes against oxidative stress via preventing the upregulation of RAGE, Keap1, and the downregulation of Nrf2, NQO1, HO1, SOD, CAT and GPx. MA also prevented increase in testicular inflammation and apoptosis, as indicated by low inflammatory (NF-κB p65, IKKß, TNF-α, IL-1ß and iNOS) and apoptosis (Bax and caspase-9), but high anti-apoptosis (Bcl-2) markers' levels. Besides, MA prevented the downregulation of testicular steroidogenic markers (3ßHSD, 17ßHSD, StAR, ARA-54 and CYP11A1). Sperm analysis revealed near normal sperm count, motility, viability, lower abnormal sperm morphology in diabetic rats received MA. MA also prevented the loss of germ cells via preventing the decreased in cell proliferative marker (PCNA) while maintaining near normal epithelial height, tubular and Leydig cell diameters in the testes in DM. MA protects the testes against damage in DM, thus maintaining spermatogenesis and steroidogenesis, consequently preserving male fertility in diabetes.


Sujet(s)
Anti-inflammatoires/pharmacologie , Antioxydants/pharmacologie , Diabète expérimental/complications , Acide myristique/pharmacologie , Spermatogenèse/effets des médicaments et des substances chimiques , Testicule/effets des médicaments et des substances chimiques , Animaux , Apoptose/effets des médicaments et des substances chimiques , Mâle , Stress oxydatif/effets des médicaments et des substances chimiques , Rats , Rat Sprague-Dawley , Testicule/cytologie , Testicule/physiologie
9.
PLoS One ; 16(2): e0247657, 2021.
Article de Anglais | MEDLINE | ID: mdl-33626104

RÉSUMÉ

Mass trapping of gravid females represents one promising strategy for the development of sustainable tools against Aedes aegypti. However, this technique requires the development of effective odorant lures that can compete with natural breeding sites. The presence of conspecific larvae has been shown to stimulate oviposition. Hence, we evaluated the role of four major molecules previously identified from Ae. aegypti larvae (isovaleric, myristoleic, myristic [i.e. tetradecanoic], and pentadecanoic acids) on the oviposition of conspecific females, as well as their olfactory perception to evaluate their range of detection. Using flight cage assays, the preference of gravid females to oviposit in water that previously contained larvae (LHW) or containing the four larval compounds was evaluated. Then, compounds and doses inducing the highest stimulation were challenged for their efficacy against LHW. Only isovaleric acid elicited antennal response, suggesting that the other compounds may act as taste cues. Pentadecanoic acid induced significant oviposition stimulation, especially when dosed at 10 ppm. Myristoleic acid and isovaleric acid deterred oviposition at 10 and 100 ppm, while no effect on oviposition was observed with myristic acid irrespectively of the dose tested. When the four compounds were pooled to mimic larvae's chemical signature, they favored oviposition at 1 ppm but negatively affected egg-laying at higher concentrations. When properly dosed, pentadecanoic acid and the blend of compounds may be promising lures for ovitraps as they could compete with LHW. Due to their low volatility, their effect should be further evaluated under field conditions, in addition with long-range attractants for developing effective tools against gravid females.


Sujet(s)
Aedes/effets des médicaments et des substances chimiques , Comportement animal/effets des médicaments et des substances chimiques , Acides gras monoinsaturés/pharmacologie , Acides gras/pharmacologie , Hémiterpènes/pharmacologie , Acide myristique/pharmacologie , Oviposition/effets des médicaments et des substances chimiques , Acides pentanoïques/pharmacologie , Animaux , Signaux , Femelle , Odorisants , Perception olfactive/effets des médicaments et des substances chimiques
10.
Biomed Pharmacother ; 133: 111043, 2021 Jan.
Article de Anglais | MEDLINE | ID: mdl-33378951

RÉSUMÉ

Nosocomial Candida colonization causes Systemic candidiasis in human with invasive infections in immunocompromised patients. Of all Candida spp., C. albicans is dominant in morbidity of all systemic candidiasis but C. tropicalis is phenomenal in mortality, virulence aspects and resistance development against antifungal drugs. The present study investigated the synergistic anti-virulent activity of myristic acid (MA) and palmitic acid (PA) against insidious dimorphic Candida spp. (C. albicans and C. tropicalis). In vitro and qPCR results revealed the mechanisms of MA-PA combination effectively inhibiting various virulence aspects such as biofilm, hyphal formation, secreted aspartyl proteases, lipases, ergosterol biosynthesis and drug effluxes. Further, in Danio rerio (Zebrafish), the MA-PA treatment increased the survival of animals and also the treated groups showed decreased level of fungal burden compared to the infected controls, after 3rd day of post infection. Histopathology of vital organs and SEM analysis of skin revealed a drastic recovery and reduced the inflammation of both Candida spp. infections in MA-PA treated animals. In addition, MA-PA treatment reduced the haemolysin and increased the susceptibility of Candida spp. in human blood model. Hence, this study suggested the therapeutic utilization of MA-PA as synergistic combination for their anti-inflammatory potency against systemic candidiasis and candidemia.


Sujet(s)
Anti-inflammatoires/pharmacologie , Antifongiques/pharmacologie , Candida albicans/effets des médicaments et des substances chimiques , Candida tropicalis/effets des médicaments et des substances chimiques , Candidose/traitement médicamenteux , Acide myristique/pharmacologie , Acide palmitique/pharmacologie , Animaux , Candida albicans/croissance et développement , Candida albicans/pathogénicité , Candida tropicalis/croissance et développement , Candida tropicalis/pathogénicité , Candidose/microbiologie , Modèles animaux de maladie humaine , Synergie des médicaments , Association de médicaments , Humains , Viabilité microbienne , Virulence , Danio zébré
11.
J Nutr ; 150(10): 2707-2715, 2020 10 12.
Article de Anglais | MEDLINE | ID: mdl-32710763

RÉSUMÉ

BACKGROUND: In the settings of primary and secondary prevention for coronary artery disease (CAD), a crucial role is played by some key molecules involved in triglyceride (TG) metabolism, such as ApoCIII. Fatty acid (FA) intake is well recognized as a main determinant of plasma lipids, including plasma TG concentration. OBJECTIVES: The aim was to investigate the possible relations between the intakes of different FAs, estimated by their plasma concentrations, and circulating amounts of ApoCIII. METHODS: Plasma samples were obtained from 1370 subjects with or without angiographically demonstrated CAD (mean ± SD age: 60.6 ± 11.0 y; males: 75.8%; BMI: 25.9 ± 4.6 kg/m2; CAD: 73.3%). Plasma lipid, ApoCIII, and FA concentrations were measured. Data were analyzed by regression models adjusted for FAs and other potential confounders, such as sex, age, BMI, diabetes, smoking, and lipid-lowering therapies. The in vitro effects of FAs were tested by incubating HepG2 hepatoma cells with increasing concentrations of selected FAs, and the mRNA and protein contents in the cells were quantified by real-time RT-PCR and LC-MS/MS analyses. RESULTS: Among all the analyzed FAs, myristic acid (14:0) showed the most robust correlations with both TGs (R = 0.441, P = 2.6 × 10-66) and ApoCIII (R = 0.327, P = 1.1 × 10-31). By multiple regression analysis, myristic acid was the best predictor of both plasma TG and ApoCIII variability. Plasma TG and ApoCIII concentrations increased progressively at increasing concentrations of myristic acid, independently of CAD diagnosis and gender. Consistent with these data, in the in vitro experiments, an ∼2-fold increase in the expression levels of the ApoCIII mRNA and protein was observed after incubation with 250 µM myristic acid. A weaker effect (∼30% increase) was observed for palmitic acid, whereas incubation with oleic acid did not affect ApoCIII protein or gene expression. CONCLUSIONS: Plasma myristic acid is associated with increased ApoCIII concentrations in cardiovascular patients. In vitro experiments indicated that myristic acid stimulates ApoCIII expression in HepG2 cells.


Sujet(s)
Apolipoprotéine C-III/sang , Maladies cardiovasculaires/sang , Acide myristique/sang , Sujet âgé , Régulation de l'expression des gènes/effets des médicaments et des substances chimiques , Cellules HepG2 , Hépatocytes/effets des médicaments et des substances chimiques , Hépatocytes/métabolisme , Humains , Mâle , Adulte d'âge moyen , Acide myristique/pharmacologie , ARN messager/génétique , ARN messager/métabolisme
12.
Mar Drugs ; 18(4)2020 Apr 18.
Article de Anglais | MEDLINE | ID: mdl-32325719

RÉSUMÉ

Wound healing is a fundamental response to tissue injury and a number of natural products has been found to accelerate the healing process. Herein, we report the preparation of a series of different polarity (organic and aqueous) extracts of the marine isopod Ceratothoa oestroides and the in vivo evaluation of their wound healing activity after topical administration of ointments incorporating the various extracts on wounds inflicted on SKH-hr1 hairless mice. The most active extract was fractionated for enrichment in the bioactive constituents and the fractions were further evaluated for their wound healing activity, while their chemical profiles were analyzed. Wound healing was evaluated by clinical assessment, photo-documentation, histopathological analysis and measurement of biophysical skin parameters, such as transepidermal water loss (TEWL), hydration, elasticity, and skin thickness. The highest levels of activity were exerted by treatment of the wounds with a fraction rich in eicosapentaenoic acid (EPA), as well as myristic and palmitoleic acids. Topical application of the bioactive fraction on the wounds of mice resulted in complete wound closure with a skin of almost normal architecture without any inflammatory elements.


Sujet(s)
Isopoda/composition chimique , Extraits tissulaires/pharmacologie , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Administration par voie topique , Animaux , Acide eicosapentanoïque/pharmacologie , Acides gras monoinsaturés/pharmacologie , Mâle , Souris , Souris hairless , Acide myristique/pharmacologie , Onguents , Peau/anatomopathologie , Extraits tissulaires/composition chimique
13.
J Sep Sci ; 43(8): 1566-1575, 2020 Apr.
Article de Anglais | MEDLINE | ID: mdl-32053742

RÉSUMÉ

Phenyl myristate was isolated from Homalium nepalense, which is known for its therapeutic virtues in traditional medicine. However, the study of radical scavenging-capacity of phenyl myristate is limited by its relatively low abundance in medicinal plants. We have studied the isolation, structure-elucidation, and bioactivities of high-performance thin-layer chromatography validated phenyl myristate from hydroalcohol-extract of bark of H. nepalense. The chemical structure of phenyl myristate was elucidated by spectroscopic methods. The chromatography was performed on high-performance thin-layer chromatography aluminum plates coated with silica-gel 60 F254 . Determination and quantitation of phenyl myristate were performed by densitometric-scanning at 254 nm (chloroform-methanol, 9:1, v/v; Rf 0.49). The method was validated according to International Council for Harmonisation guidelines in terms of linearity, specificity, sensitivity, accuracy, precision, robustness, and stability. Linearity-range of phenyl myristate was 100-500 ng/5 µL with correlation-coefficient r2  = 0.9997. Limits of detection and quantitation were 3.35 and 10.17 ng, respectively. Phenyl myristate showed significant free-radical-scavenging activities in 2,2-diphenyl-1-picrylhydrazyl, oxygen-radical-absorbance-capacity, and ex vivo cell-based-antioxidant-protection-in-erythrocytes assays. Molecular-docking approach of phenyl myristate showed effective binding at active sites of human serum albumin (HSA) with the lowest binding energy (-8.4 kcal/mol) that was comparable with ascorbic acid (-5.0 kcal/mol). These studies provide mechanistic insight into the potential free radical scavenging activities of phenyl myristate.


Sujet(s)
Piégeurs de radicaux libres/analyse , Simulation de docking moléculaire , Acide myristique/analyse , Extraits de plantes/analyse , Salicaceae/composition chimique , Dérivés du biphényle/antagonistes et inhibiteurs , Chromatographie sur couche mince , Érythrocytes/effets des médicaments et des substances chimiques , Piégeurs de radicaux libres/pharmacologie , Humains , Structure moléculaire , Acide myristique/pharmacologie , Picrates/antagonistes et inhibiteurs , Extraits de plantes/pharmacologie
14.
Prostaglandins Other Lipid Mediat ; 149: 106423, 2020 08.
Article de Anglais | MEDLINE | ID: mdl-32006664

RÉSUMÉ

Saturated fatty acids (SFA) have been known to trigger inflammatory signaling in metabolic tissues; however, the effects of specific SFAs in the intestinal epithelium have not been well studied. Several previous studies have implicated disruptions in sphingolipid metabolism by oversupply of SFAs in inflammatory process. Also, our previous studies have implicated sphingosine kinase 1 (SK1) and its product sphingosine-1-phosphate (S1P) as having key roles in the regulation of inflammatory processes in the intestinal epithelium. Therefore, to define the role for specific SFAs in inflammatory responses in intestinal epithelial cells, we examined myristate (C14:0) and palmitate (C16:0). Myristate, but not palmitate, significantly induced the pro-inflammatory cytokine tumor necrosis factor α (TNFα), and it was SK1-dependent. Interestingly, myristate-induced TNFα expression was not suppressed by inhibition of S1P receptors (S1PRs), hinting at a potential novel intracellular target of S1P. Additionally, myristate regulated the expression of TNFα via JNK activation in an SK1-dependent manner, suggesting a novel S1PR-independent target as a mediator between SK1 and JNK in response to myristate. Lastly, a myristate-enriched milk fat-based diet (MFBD) increased expression of TNFα in colon tissues and elevated the S1P to sphingosine ratio, demonstrating the potential of myristate-involved pathobiologies in intestinal tissues. Taken together our studies suggest that myristate regulates the expression of TNFα in the intestinal epithelium via regulation of SK1 and JNK.


Sujet(s)
Régulation de l'expression des gènes/effets des médicaments et des substances chimiques , Muqueuse intestinale/cytologie , Acide myristique/pharmacologie , Phosphotransferases (Alcohol Group Acceptor)/métabolisme , Facteur de nécrose tumorale alpha/génétique , Animaux , Lignée cellulaire tumorale , Cyclooxygenase 2/génétique , Femelle , Humains , Mâle , Souris , Rats
15.
Mitochondrion ; 50: 1-13, 2020 01.
Article de Anglais | MEDLINE | ID: mdl-31655165

RÉSUMÉ

Patients affected by very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency commonly present liver dysfunction whose pathogenesis is poorly known. We demonstrate here that major metabolites accumulating in this disorder, namely cis-5-tetradecenoic acid (Cis-5) and myristic acid (Myr), markedly impair mitochondrial respiration, decreasing ATP production in liver mitochondrial preparations from adolescent rats. Other parameters of mitochondrial homeostasis such as membrane potential (ΔΨm) and Ca2+retention capacity were strongly compromised by these fatty acids, involving induction of mitochondrial permeability transition. The present data indicate that disruption of mitochondrial bioenergetics and Ca2+homeostasis may contribute to the liver dysfunction of VLCAD deficient patients.


Sujet(s)
Foie/effets des médicaments et des substances chimiques , Potentiel de membrane mitochondriale/effets des médicaments et des substances chimiques , Potentiel de membrane mitochondriale/physiologie , Mitochondries du foie/physiologie , Vieillissement , Animaux , Calcium/métabolisme , Cytochromes c/métabolisme , Cellules HepG2 , Hépatocytes/effets des médicaments et des substances chimiques , Hépatocytes/métabolisme , Humains , Foie/métabolisme , Mâle , Mitochondries du foie/effets des médicaments et des substances chimiques , Acide myristique/pharmacologie , Rats , Rat Wistar
16.
Sci Rep ; 9(1): 14926, 2019 10 17.
Article de Anglais | MEDLINE | ID: mdl-31624310

RÉSUMÉ

Deep eutectic solvents have been recently reported as an interesting alternative to improve the therapeutic efficacy of conventional drugs, hence called therapeutic deep eutectic solvents (THEDES). The main objective of this work was to evaluate the potential of limonene (LIM) based THEDES as new possible systems for cancer treatment. LIM is known to have antitumor activity, however it is highly toxic and cell viability is often compromised, thus this compound is not selective towards cancer cells. Different THEDES based on LIM were developed to unravel the anticancer potential of such systems. THEDES were prepared by gently mixing saturated fatty acids menthol or ibuprofen (IBU) with LIM. Successful THEDES were obtained for Menthol:LIM (1:1), CA:LIM (1:1), IBU:LIM (1:4) and IBU:LIM(1:8). The results indicate that all the THEDES present antiproliferative properties, but IBU:LIM (1:4) was the only formulation able to inhibit HT29 proliferation without comprising cell viability. Therefore, IBU:LIM (1:4) was the formulation selected for further assessment of anticancer properties. The results suggest that the mechanism of action of LIM:IBU (1:4) is different from isolated IBU and LIM, which suggest the synergetic effect of DES. In this work, we unravel a methodology to tune the selectivity of LIM towards HT29 cell line without compromising cell viability of healthy cells. We demonstrate furthermore that coupling LIM with IBU leads also to an enhancement of the anti-inflammatory activity of IBU, which may be important in anti-cancer therapies.


Sujet(s)
Antinéoplasiques/pharmacologie , Prolifération cellulaire/effets des médicaments et des substances chimiques , Liquides ioniques/pharmacologie , Limonène/pharmacologie , Tumeurs/traitement médicamenteux , Antinéoplasiques/composition chimique , Antinéoplasiques/usage thérapeutique , Cellules Caco-2 , Survie cellulaire/effets des médicaments et des substances chimiques , Acides capriques/composition chimique , Acides capriques/pharmacologie , Acides capriques/usage thérapeutique , Préparation de médicament/méthodes , Tests de criblage d'agents antitumoraux , Cellules HT29 , Humains , Ibuprofène/composition chimique , Ibuprofène/pharmacologie , Ibuprofène/usage thérapeutique , Liquides ioniques/composition chimique , Liquides ioniques/usage thérapeutique , Limonène/composition chimique , Limonène/usage thérapeutique , Menthol/composition chimique , Menthol/pharmacologie , Menthol/usage thérapeutique , Acide myristique/composition chimique , Acide myristique/pharmacologie , Acide myristique/usage thérapeutique , Tumeurs/anatomopathologie
17.
J Proteomics ; 208: 103503, 2019 09 30.
Article de Anglais | MEDLINE | ID: mdl-31454558

RÉSUMÉ

Candida albicans, a dimorphic opportunistic fungus is known to form robust biofilm and commonly associated with superficial and life threatening systemic infections. The repertoire of C. albicans infection is comprehensive due to its biofilm mediated virulence and occurrence of resistance against conventional antifungal drugs. Natural bioactive compounds are known for their antivirulence potency against fungi circumventing their resistance. In the present study, antibiofilm and antihyphal efficacies of myristic acid (MA), a major component of Myristica fragrans against C. albicans was assessed. Results of biofilm assays, optical microscopic analyses showed the potent inhibition of biofilm and hyphal formation by MA at 125 µg mL-1. Proteomic analysis revealed the ability of MA to target proteins involved in various virulence pathways such as ergosterol synthesis, sphingolipid metabolism, multidrug resistance and the oxidative stress. The results of gene expression analysis and biochemical assays validated the outcomes of proteomic analysis. This investigation emphasized the potent antibiofilm and virulence inhibitory potentials of MA. Hence, MA could be clinically utilized to control infections caused by C. albicans. BIOLOGICAL SIGNIFICANCE: The conventional antifungal drugs acquire single target pattern by regulating either sterol synthesis or drug efflux pump in C. albicans that ushers drug-resistance. But Myristic acid attenuates C. albicans virulence by negative regulation of proteins involved in sterol synthesis & uptake, sphingolipids and antioxidant activity. In the current study, the multi-target efficacy and the ability to inhibit biofilm and hyphae mediated virulence factors without affecting the cellular metabolism of C. albicans marks myristic acid as a potent anti-candida agent against drug resistant Candida species.


Sujet(s)
Biofilms/effets des médicaments et des substances chimiques , Candida albicans , Ergostérol/biosynthèse , Protéines fongiques/métabolisme , Acide myristique/pharmacologie , Stress oxydatif/effets des médicaments et des substances chimiques , Protéomique , Sphingolipides/biosynthèse , Biofilms/croissance et développement , Candida albicans/pathogénicité , Candida albicans/physiologie , Hyphae/métabolisme
18.
Appl Microbiol Biotechnol ; 103(13): 5367-5377, 2019 Jul.
Article de Anglais | MEDLINE | ID: mdl-31053917

RÉSUMÉ

The bacterium, Bacillus amyloliquefaciens Pc3, was previously isolated from Antarctic seawater and has been found to show antagonistic activity against the fungus, Rhizoctonia solani ACCC 36316, which causes a severe disease known as Sclerotinia sclerotiorum in rapeseed plants. Bacillus lipopeptides had been widely used as biocontrol agents for plant diseases. In this study, we isolated 11 lipopeptide compounds from B. amyloliquefaciens Pc3 culture broth via reversed-phase high-performance liquid chromatography (RP-HPLC) and used matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to identify these as iturin A (C14, C15, C16, C17), fengycin B (C14, C15, C16, C17), and surfactin (C14, C15, C16). We further found that the addition of exogenous alkanoic acids, including myristic acid, pentadecanoic acid, palmitic acid, heptadecanoic acid, octadecanoic acid, and nonadecanoic acid, to the bacterial growth media could promote lipopeptide production and enhance the antifungal activities of crude lipopeptide extracts from B. amyloliquefaciens Pc3. In addition, the transcriptional levels of three lipopeptide synthesis genes, ituD, fenA, and srfA-A, and two fatty acid metabolism-related genes, FabI, which encodes enoyl-ACP reductase, and FadB, which encodes enoyl-CoA hydratase, were found to be upregulated in cells grown with exogenous alkanoic acids. Among the six alkanoic acids tested, those with odd carbon chain lengths had a greater effect on lipopeptide production, antifungal activity, and target gene upregulation than those with even carbon chain lengths. These results provide a practical approach for the efficient production of lipopeptides in Bacillus amyloliquefaciens Pc3.


Sujet(s)
Antibiose , Antifongiques/pharmacologie , Bacillus amyloliquefaciens/effets des médicaments et des substances chimiques , Bacillus amyloliquefaciens/métabolisme , Acides carboxyliques/pharmacologie , Lipopeptides/biosynthèse , Bacillus amyloliquefaciens/génétique , Acides gras/pharmacologie , Lipopeptides/isolement et purification , Acide myristique/pharmacologie , Peptides cycliques/isolement et purification , Rhizoctonia/effets des médicaments et des substances chimiques
19.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(7): 1031-1038, 2019 07.
Article de Anglais | MEDLINE | ID: mdl-30980919

RÉSUMÉ

Decreased levels of the δ isozyme of diacylglycerol kinase (DGK) in skeletal muscle attenuate glucose uptake and, consequently, are critical for the pathogenesis of type 2 diabetes. We recently found that free myristic acid (14:0), but not free palmitic acid (16:0), increased the DGKδ protein levels and enhanced glucose uptake in C2C12 myotube cells. However, it has been unclear how myristic acid regulates the level of DGKδ2 protein. In the present study, we characterized the myristic acid-dependent increase of DGKδ protein. A cycloheximide chase assay demonstrated that myristic acid, but not palmitic acid, markedly stabilized DGKδ protein. Moreover, other DGK isozymes, DGKη and ζ, as well as glucose uptake-related proteins, such as protein kinase C (PKC) α, PKCζ, Akt and glycogen synthase kinase 3ß, failed to be stabilized by myristic acid. Furthermore, DGKδ was not stabilized in cultured hepatocellular carcinoma cells, pancreas carcinoma cells or neuroblastoma cells, and only a moderate stabilizing effect was observed in embryonic kidney cells. A proteasome inhibitor and a lysosome inhibitor, MG132 and chloroquine, respectively, partly inhibited DGKδ degradation, suggesting that myristic acid prevents, at least in part, the degradation of DGKδ by the ubiquitin-proteasome system and the autophagy-lysosome pathway. Overall, these results strongly suggest that myristic acid attenuates DGKδ protein degradation in skeletal muscle cells and that this attenuation is fatty acid-, protein- and cell line-specific. These new findings provide novel insights into the molecular mechanisms of the pathogenesis of type 2 diabetes mellitus.


Sujet(s)
Diacylglycérol kinase/métabolisme , Muscles squelettiques/cytologie , Acide myristique/pharmacologie , Stabilité protéique/effets des médicaments et des substances chimiques , Animaux , Lignée cellulaire , Diabète de type 2/étiologie , Glucose/pharmacocinétique , Humains , Isoenzymes/métabolisme , Souris , Muscles squelettiques/métabolisme , Protéolyse/effets des médicaments et des substances chimiques
20.
J Antibiot (Tokyo) ; 72(5): 298-305, 2019 05.
Article de Anglais | MEDLINE | ID: mdl-30787402

RÉSUMÉ

Listeria monocytogenes (L. monocytogenes), an important food-borne pathogenic microorganism, has resistance immune function to many commonly used drugs. Myristic acid is a traditional Chinese herbal medicine, but it has been rarely used as a food additive, limiting the development of natural food preservatives. In this study, the antibacterial activity and mechanism of myristic acid against L. monocytogenes were studied. The minimum inhibitory concentration (MIC) of myristic acid against 13 L. monocytogenes strains ranged from 64 to 256 µg ml-1. The time-kill assay demonstrated that when myristic acid was added to dairy products, flow cytometry confirmed that myristic acid influenced cell death and inhibited the growth of L. monocytogenes. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and NPN uptake studies illustrated that myristic acid changed the bacterial morphology and membrane structure of L. monocytogenes, which led to rapid cell death. Myristic acid could bind to DNA and lead to changes in DNA conformation and structure, as identified by fluorescence spectroscopy. Our studies provide additional evidence to support myristic acid being used as a natural antibacterial agent and also further fundamental understanding of the modes of antibacterial action.


Sujet(s)
Antibactériens/pharmacologie , Listeria monocytogenes/effets des médicaments et des substances chimiques , Lait/microbiologie , Acide myristique/pharmacologie , Animaux , Membrane cellulaire/effets des médicaments et des substances chimiques , Transmission de maladie infectieuse , Cytométrie en flux , Listeria monocytogenes/cytologie , Listeria monocytogenes/croissance et développement , Listeria monocytogenes/physiologie , Tests de sensibilité microbienne , Viabilité microbienne/effets des médicaments et des substances chimiques , Microscopie électronique à balayage , Microscopie électronique à transmission , Conformation d'acide nucléique/effets des médicaments et des substances chimiques , Spectrométrie de fluorescence
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