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Molecules (Basel, Switzerland) Jun 2024Non-alcoholic fatty liver disease (NAFLD) is a significant hepatic condition that has gained worldwide attention. Kaempferol (Kae), renowned for its diverse biological...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is a significant hepatic condition that has gained worldwide attention. Kaempferol (Kae), renowned for its diverse biological activities, including anti-inflammatory, antioxidant, anti-aging, and cardio-protective properties, has emerged as a potential therapeutic candidate for non-alcoholic steatohepatitis (NASH). Despite its promising therapeutic potential, the precise underlying mechanism of Kae's beneficial effects in NASH remains unclear. Therefore, this study aims to clarify the mechanism by conducting comprehensive in vivo and in vitro experiments.
RESULTS
In this study, a murine model of non-alcoholic steatohepatitis (NASH) was established by feeding C57BL/6 female mice a high-fat diet for 12 weeks. Kaempferol (Kae) was investigated for its ability to modulate systemic inflammatory responses and lipid metabolism in this model (20 mg/kg per day). Notably, Kae significantly reduced the expression of NLRP3-ASC/TMS1-Caspase 3, a crucial mediator of liver tissue inflammation. Additionally, in a HepG2 cell model induced with palmitic acid/oleic acid (PA/OA) to mimic NASH conditions, Kae demonstrated the capacity to decrease lipid droplet accumulation and downregulate the expression of NLRP3-ASC/TMS1-Caspase 3 (20 µM and the final concentration to 20 nM). These findings suggest that Kae may hold therapeutic potential in the treatment of NASH by targeting inflammatory and metabolic pathways.
CONCLUSIONS
These findings suggest that kaempferol holds potential as a promising therapeutic intervention for ameliorating non-alcoholic fatty liver disease (NAFLD).
Topics: Kaempferols; Non-alcoholic Fatty Liver Disease; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Mice; Humans; Signal Transduction; Caspase 3; Female; Neutrophils; Disease Models, Animal; Mice, Inbred C57BL; Liver; Hep G2 Cells; Diet, High-Fat
PubMed: 38893506
DOI: 10.3390/molecules29112630 -
Molecules (Basel, Switzerland) May 2024This study investigates the chemical composition, nutritional, and biological properties of extracts obtained from berries using different extraction methods and...
This study investigates the chemical composition, nutritional, and biological properties of extracts obtained from berries using different extraction methods and solvents. Hydrodistillation and supercritical fluid extraction with CO allowed us to isolate fruit essential oil (HD) and fixed oil (SFE), respectively. A phenol-enriched extract was obtained using a mild ultrasound-assisted maceration with methanol (UAM). The HD most abundant component, using gas chromatography-mass spectrometry (GC/MS), was italicene epoxide (17.2%), followed by hexadecanoic acid (12.4%), khusinol (10.5%), limonene (9.7%), dodecanoic acid (9.7%), and (E)-anethole (6.1%). Linoleic (348.9 mg/g of extract, 70.5%), oleic (88.9 mg/g, 17.9%), and palmitic (40.8 mg/g, 8.2%) acids, followed by α-linolenic and stearic acids, were the main fatty acids in SFE determined using high-performance liquid chromatography coupled with a photodiode array detector and an evaporative light scattering detector (HPLC-DAD/ELSD). HPLC-DAD analyses of SFE identified β-carotene as the main carotenoid (1.7 mg/g), while HPLC with fluorescence detection (FLU) evidenced α-tocopherol (1.2 mg/g) as the most abundant tocopherol isoform in SFE. Liquid chromatography-electrospray ionization-MS (LC-ESI-MS) analysis of UAM showed the presence of quercetin-sulfate (15.6%, major component), malvidin 3--(6--p-coumaroyl) glucoside-4-vinylphenol adduct (pigment B) (9.3%), di-caffeoyl coumaroyl spermidine (7.6%), methyl-epigallocatechin (5.68%), and phloretin (4.1%), while flavonoids (70.5%) and phenolic acids (23.9%) emerged as the most abundant polyphenol classes. UAM exerted a complete inhibition of the cholesterol oxidative degradation at 140 °C from 75 μg of extract, showing 50% protection at 30.6 μg (IA). Furthermore, UAM significantly reduced viability (31-48%) in A375 melanoma cells in the range of 500-2000 μg/mL after 96 h of incubation (MTT assay), with a low toxic effect in normal HaCaT keratinocytes. The results of this research extend the knowledge of the nutritional and biological properties of berries, providing useful information on specific extracts for potential food, cosmetic, and pharmaceutical applications.
Topics: Plant Extracts; Fruit; Photinia; Humans; Antioxidants; Fatty Acids; Oils, Volatile; Gas Chromatography-Mass Spectrometry; Chromatography, High Pressure Liquid; Phytochemicals
PubMed: 38893452
DOI: 10.3390/molecules29112577 -
Molecules (Basel, Switzerland) May 2024Metabolic reprogramming mediates antibiotic efficacy. However, metabolic adaptation of microbes evolving from antibiotic sensitivity to resistance remains undefined....
Metabolic reprogramming mediates antibiotic efficacy. However, metabolic adaptation of microbes evolving from antibiotic sensitivity to resistance remains undefined. Therefore, untargeted metabolomics was conducted to unveil relevant metabolic reprogramming and potential intervention targets involved in gentamicin resistance. In total, 61 metabolites and 52 metabolic pathways were significantly altered in gentamicin-resistant . Notably, the metabolic reprogramming was characterized by decreases in most metabolites involved in carbohydrate and amino acid metabolism, and accumulation of building blocks for nucleotide synthesis in gentamicin-resistant . Meanwhile, fatty acid metabolism and glycerolipid metabolism were also significantly altered in gentamicin-resistant . Additionally, glycerol, glycerol-3-phosphate, palmitoleate, and oleate were separately defined as the potential biomarkers for identifying gentamicin resistance in . Moreover, palmitoleate and oleate could attenuate or even abolished killing effects of gentamicin on , and separately increased the minimum inhibitory concentration of gentamicin against by 2 and 4 times. Furthermore, palmitoleate and oleate separately decreased intracellular gentamicin contents, and abolished gentamicin-induced accumulation of reactive oxygen species, indicating involvement of gentamicin metabolism and redox homeostasis in palmitoleate/oleate-promoted gentamicin resistance in . This study identifies the metabolic reprogramming, potential biomarkers and intervention targets related to gentamicin resistance in bacteria.
Topics: Gentamicins; Escherichia coli; Oleic Acid; Drug Resistance, Bacterial; Anti-Bacterial Agents; Fatty Acids, Monounsaturated; Microbial Sensitivity Tests; Metabolomics; Metabolic Networks and Pathways; Reactive Oxygen Species; Up-Regulation
PubMed: 38893378
DOI: 10.3390/molecules29112504 -
Nutrients May 2024In this study, we prepared fermented products of isoflavone-enriched soybean leaves (IESLs) and analyzed their nutrients, isoflavones, anti-obesity efficacy, and effects...
In this study, we prepared fermented products of isoflavone-enriched soybean leaves (IESLs) and analyzed their nutrients, isoflavones, anti-obesity efficacy, and effects on gut microbiota. Fermented IESLs (FIESLs) were found to be rich in nutrients, especially lauric acid, oleic acid, and linoleic acid. In addition, the concentrations of most essential free amino acids were increased compared to those of IESLs. The contents of bioactive compounds, such as total phenolic, total flavonoid, daidzein, and genistein, significantly increased as well. In addition, FIESLs administration in a high-fat diet (HFD) animal model improved the final body weight, epididymal fat, total lipid, triglyceride, total cholesterol, blood glucose, and leptin levels, as well as reverting microbiota dysbiosis. In conclusion, these findings indicate that FIESLs have the potential to inhibit obesity caused by HFDs and serve as a modulator of gut microbiota, offering the prevention of diet-induced gut dysbiosis and metabolite diseases associated with obesity.
Topics: Gastrointestinal Microbiome; Glycine max; Animals; Plant Leaves; Fermentation; Isoflavones; Obesity; Male; Diet, High-Fat; Anti-Obesity Agents; Lactic Acid; Mice, Inbred C57BL; Mice; Dysbiosis
PubMed: 38892626
DOI: 10.3390/nu16111693 -
Nutrients May 2024Breast milk (BM) plays a crucial role in providing essential fatty acids (FA) and energy for the growing infant. When the mother's own BM is not available, nutritional...
Breast milk (BM) plays a crucial role in providing essential fatty acids (FA) and energy for the growing infant. When the mother's own BM is not available, nutritional recommendations suggest donor milk (DM) in clinical and home practices. BM was collected from a variety of donor mothers in different lactation stages. Holder pasteurization (HoP) eliminates potential contaminants to ensure safety. FA content of BM samples from the Breast Milk Collection Center of Pécs, Hungary, were analyzed before and after HoP. HoP decreases the level of C6:0, C8:0, C14:1n-5c, C18:1n-9c, C18:3n-6c, C18:3n-3c, and C20:4n-6c in BM, while C14:0, C16:0, C18:1n-9t, C22:0, C22:1n-9c, C24:0, C24:1n-9c, and C22:6n-3c were found in elevated concentration after HoP. We did not detect time-dependent concentration changes in FAs in the first year of lactation. BM produced for girl infants contains higher C20:2n-6c levels. In the BM of mothers who delivered via cesarean section, C12:0, C15:0, C16:0, C17:0, C18:0, C18:1n-9t, C22:1n-9c levels were higher, while C18:2n-6c, C22:0, C24:0, and C22:6n-3c concentrations were lower compared to mothers who gave birth spontaneously. FAs in BM are constant during the first year of lactation. Although HoP modifies the concentration of different FAs, pasteurized DM provides essential FAs to the developing infant. Current data providing information about the FA profile of BM gives origination to supplementation guidelines.
Topics: Humans; Milk, Human; Female; Pasteurization; Fatty Acids; Infant; Adult; Infant, Newborn; Sex Factors; Pregnancy; Lactation; Delivery, Obstetric; Hungary; Milk Banks
PubMed: 38892622
DOI: 10.3390/nu16111689 -
International Journal of Molecular... May 2024Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes,...
Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes, excluding alcohol and other known liver injury factors. However, there are no specific drugs for the clinical treatment of NAFLD. Therefore, research on the pathogenesis of NAFLD at the cellular and molecular levels is a promising approach to finding therapeutic targets and developing targeted drugs for NAFLD. Pin1 is highly expressed during adipogenesis and contributes to adipose differentiation, but its specific mechanism of action in NAFLD is unclear. In this study, we investigated the role of Pin1 in promoting the development of NAFLD and its potential mechanisms in vitro and in vivo. First, Pin1 was verified in the NAFLD model in vitro using MCD diet-fed mice by Western Blot, RT-qPCR and immunohistochemistry (IHC) assays. In the in vitro study, we used the oleic acid (OA) stimulation-induced lipid accumulation model and examined the lipid accumulation in each group of cells by oil red O staining as well as BODIPY staining. The results showed that knockdown of Pin1 inhibited lipid accumulation in hepatocytes in an in vitro lipid accumulation model and improved lipid indices and liver injury levels. Moreover, in vivo, WT and Pin1-KO mice were fed a methionine-choline deficient (MCD) diet for 4 weeks to induce the NAFLD model. The effects of Pin1 on lipid accumulation, hepatic fibrosis, and oxidative stress were evaluated by biochemical analysis, glucose and insulin tolerance tests, histological analysis, IHC, RT-qPCR and Western blot assays. The results indicate that Pin1 knockdown significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NAFLD mice, improved glucose tolerance and alleviated insulin resistance in mice. Further studies showed that the AMPK/ACC1 signalling pathway might take part in the process by which Pin1 regulates NAFLD, as evidenced by the inhibition of the AMPK/ACC1 pathway. In addition, immunofluorescence (IF), coimmunoprecipitation (Co-IP) and GST pull-down experiments also showed that Pin1 interacts directly with ACC1 and inhibits ACC1 phosphorylation levels. Our study suggests that Pin1 promotes NAFLD progression by inhibiting the activation of the AMPK/ACC1 signalling pathway, and it is possible that this effect is achieved by Pin1 interacting with ACC1 and inhibiting the phosphorylation of ACC1.
Topics: Animals; NIMA-Interacting Peptidylprolyl Isomerase; Non-alcoholic Fatty Liver Disease; Mice; Male; Mice, Knockout; Hepatocytes; Humans; Lipid Metabolism; Mice, Inbred C57BL; Disease Models, Animal; Protein Binding; Acetyl-CoA Carboxylase
PubMed: 38892011
DOI: 10.3390/ijms25115822 -
Cells Jun 2024Precise control of neuronal activity is crucial for the proper functioning of neurons. How lipid homeostasis contributes to neuronal activity and how much of it is...
Precise control of neuronal activity is crucial for the proper functioning of neurons. How lipid homeostasis contributes to neuronal activity and how much of it is regulated by cells autonomously is unclear. In this study, we discovered that absence of the lipid regulator , a functional ortholog of the peroxisome proliferator-activated receptor (PPAR) in , resulted in defective pathogen avoidance behavior against (PA14). Functional NHR-49 was required in the neurons, and more specifically, in a set of oxygen-sensing body cavity neurons, URX, AQR, and PQR. We found that lowering the neuronal activity of the body cavity neurons improved avoidance in mutants. Calcium imaging in URX neurons showed that mutants displayed longer-lasting calcium transients in response to an O upshift, suggesting that excess neuronal activity leads to avoidance defects. Cell-specific rescue of NHR-49 in the body cavity neurons was sufficient to improve pathogen avoidance, as well as URX neuron calcium kinetics. Supplementation with oleic acid also improved avoidance behavior and URX calcium kinetics, suggesting that the defective calcium response in the neuron is due to lipid dysfunction. These findings highlight the role of cell-autonomous lipid regulation in neuronal physiology and immune behavior.
Topics: Animals; Caenorhabditis elegans; Lipid Metabolism; Caenorhabditis elegans Proteins; Neurons; Pseudomonas aeruginosa; Calcium; Mutation; Avoidance Learning; Receptors, Cytoplasmic and Nuclear
PubMed: 38891110
DOI: 10.3390/cells13110978 -
Foods (Basel, Switzerland) May 2024Palm oil has a bad reputation due to the exploitation of farmers and the destruction of endangered animal habitats. Therefore, many consumers wish to avoid the use of...
Palm oil has a bad reputation due to the exploitation of farmers and the destruction of endangered animal habitats. Therefore, many consumers wish to avoid the use of palm oil. Decorative sugar contains a small amount of palm oil to prevent the sugar from melting on hot bakery products. High-oleic sunflower oil used as a substitute for palm oil was analyzed in this study via multispectral imaging and an electronic nose, two methods suitable for potential large-batch analysis of sugar/oil coatings. Multispectral imaging is a nondestructive method for comparing the wavelength reflections of the surface of a sample. Reference samples enabled the estimation of the quality of unknown samples, which were confirmed via acid value measurements. Additionally, for quality determination, volatile compounds from decorative sugars were measured with an electronic nose. Both applications provide comparable data that provide information about the quality of decorative sugars.
PubMed: 38890921
DOI: 10.3390/foods13111693 -
Foods (Basel, Switzerland) May 2024The objective of this research was to investigate and compare the results obtained in the intensification and integration of (sc-CO) under different pressure conditions...
Intensification of the SFE Using Ethanol as a Cosolvent and Integration of the SFE Process with sc-CO Followed by PLE Using Pressurized Ethanol of Black Soldier Fly ( L.) Larvae Meal-Extract Yields and Characterization.
The objective of this research was to investigate and compare the results obtained in the intensification and integration of (sc-CO) under different pressure conditions (25 and 30 MPa) at 60 °C. When intensifying the process, ethanol (10%) was used as a co-solvent (sc-CO + EtOH). In the process integration, black soldier fly larvae flour, defatted via supercritical extraction (SFE), was the raw material for pressurized liquid extraction (PLE) using ethanol as solvent. The extract yields, fatty acid profile, free fatty acids, triacylglycerols (TAGs), oxidative stability, and nutritional quality of the oil obtained using sc-CO + EtOH were evaluated. The composition of bioactive compounds (carotenoids, acidity, antioxidant compounds, tocopherols, and phospholipids) was determined in both extracts. The yields of the extracts were different by 32.5 to 53.9%. In the extracts obtained with sc-CO + EtOH (10%), the predominant fatty acids were oleic, palmitic, and linoleic, with considerable levels of desirable fatty acids (DFA), tocopherols, and phospholipids. The nutritional indices showed good values for polyunsaturated and saturated fatty acids (PUFAs/SFAs), above 0.45%. Extracts from larvae meal defatted with SFE showed carotenoids, phenolic compounds, and antioxidant activity. HPTLC and HPLC analyses indicated the presence of amino acids, sugars, phenolics, and organic acids in their composition. This study revealed that the supercritical fluid extraction (SFE) process, or its conditions, can modify the fatty acid composition and the presence of minor bioactive compounds in the obtained extracts.
PubMed: 38890848
DOI: 10.3390/foods13111620 -
European Journal of Immunology Jun 2024Unsaturated fatty acids (UFA) are crucial for T-cell effector functions, as they can affect the growth, differentiation, survival, and function of T cells. Nonetheless,...
Unsaturated fatty acids (UFA) are crucial for T-cell effector functions, as they can affect the growth, differentiation, survival, and function of T cells. Nonetheless, the mechanisms by which UFA affects T-cell behavior are ill-defined. Therefore, we analyzed the processing of oleic acid, a prominent UFA abundantly present in blood, adipocytes, and the fat pads surrounding lymph nodes, in CD4 T cells. We found that exogenous oleic acid increases proliferation and enhances the calcium flux response upon CD3/CD28 activation. By using a variety of techniques, we found that the incorporation of oleic acid into membrane lipids, rather than regulation of cellular metabolism or TCR expression, is essential for its effects on CD4 T cells. These results provide novel insights into the mechanism through which exogenous oleic acid enhances CD4 T-cell function.
PubMed: 38890809
DOI: 10.1002/eji.202350685