RESUMO
Esterification of anthocyanins with saturated fatty acids have been widely investigated, while that with unsaturated fatty acids is little understood. In this study, crude extract (purity â¼ 35 %) of cyanidin-3-O-glucoside (C3G) from black bean seed coat was utilized as reaction substrate, and enzymatically acylated with unsaturated fatty acid (oleic acid). Optimization of various reaction parameters finally resulted in the highest acylation rate of 54.3 %. HPLC-MS/MS and NMR analyses elucidated the structure of cyanidin-3-O-glucoside-oleic acid ester (C3G-OA) to be cyanidin-3-O-(6â³-octadecene)-glucoside. Introduction of oleic acid into C3G improved the lipophilicity, antioxidant ability, and antibacterial activity. Further, the color and substance stability analyses showed that the susceptibility of C3G and C3G-OA to different thermal, peroxidative, and illuminant treatments were highly pH dependent, which suggested individual application guidelines. Moreover, C3G-OA showed lower toxicity to normal cell (QSG-7701) and better inhibitory effect on the proliferation of HepG2 cells than C3G, which indicated its potential anti-tumor bioactivity.
Assuntos
Antocianinas , Ácido Oleico , Antocianinas/química , Humanos , Ácido Oleico/química , Esterificação , Extratos Vegetais/química , Antioxidantes/química , Antioxidantes/farmacologia , Células Hep G2 , Phaseolus/química , Antibacterianos/química , Antibacterianos/farmacologia , Estrutura MolecularRESUMO
The objective of this study was to systematically elucidate the effects of conventional (Cold Pressing, CP; Hot Pressing, HP; Soxhlet Extraction; SE) and novel methods (Microwave-Assisted Extraction, MAE) on the physicochemical properties, bio-active substances, flavor and lipidomics of Camellia oleifera oil (COO). The cold-pressed COO contained the highest contents of squalene (176.38 mg/kg), α-tocopherol (330.52 mg/kg), polyphenols (68.33 mg/kg) and phytosterols (2782.55 mg/kg). Oleic acid was observed as the predominant fatty acid with the content of approximately 80%. HS-GC-IMS identified 47 volatile compounds, including 11 aldehydes, 11 ketones, 11 alcohols, 2 acids, 8 esters, 2 pyrazines, 1 furan, and 1 thiophene. A total of 5 lipid classes and 30 lipid subclasses of 339 lipids were identifed, among which TGs and DGs were observed as the major lipids. In summary, both cold-pressed and microwave-assisted technologies provided high-quality COO with high content of bio-active substances and diglycerides/triglycerides.
Assuntos
Camellia , Lipidômica , Óleos de Plantas/química , Ácidos Graxos , Ácido Oleico , Camellia/químicaRESUMO
BACKGROUND: Breast cancer survivors are a growing population due to improved treatment. It is known that postmenopausal women treated for breast cancer may experience weight gain and increased insulin resistance, but detailed knowledge on how chemotherapy impact metabolic and endocrine mechanisms remain unknown. OBJECTIVES: We performed a thorough, preliminary study to elucidate the differing mechanisms of postprandial absorption and metabolism in postmenopausal early breast cancer (EBC) patients treated with adjuvant chemotherapy compared to healthy controls. We hypothesize that chemotherapy has a negative impact on metabolism in EBC patients. METHODS: We examined four postmenopausal women shortly after treatment with chemotherapy for EBC and four age-matched healthy women who served as controls using isotopic tracers during a mixed meal-test. Blood was sampled during the 240 min meal-test to examine postprandial absorption and endogenous synthesis of lipid and carbohydrate metabolites. RESULTS: We found that insulin concentrations were numerically higher before the meal-test in the EBC patients compared to controls (76.3 pmol/L vs 37.0 pmol/L; P = 0.06). Glucose kinetics was increased postprandial (most pronounced at 30 min, 9.46 mmol/L vs 7.33 mmol/L; P = 0.51), with no difference between the groups regarding liver glucose output. Fatty acid kinetics showed a numeric increase in oleic acid rate of appearance in BC patients, but only during the first hour after the mixed meal. There was no significant difference in VLDL-TAG synthesis between the two groups. CONCLUSIONS: This preliminary study is unique in using advanced tracer methods to investigate in vivo metabolism of EBC patients after chemotherapy although no statistical differences in glucose and fatty acid kinetics was seen compared to controls. However, during the first two postprandial hours, oral glucose and oleic acid appearance in the systematic circulation was elevated in the EBC patients. This could be due to changes in gastrointestinal uptake and further studies with altered set-up could provide valuable insights.
Assuntos
Neoplasias da Mama , Glucose , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Ácido Oleico , Pós-Menopausa , Dados Preliminares , Glicemia/metabolismo , Insulina , Ácidos Graxos , Período Pós-Prandial , TriglicerídeosRESUMO
The increasing antimicrobial resistance requires continuous investigation of new antimicrobial agents preferably derived from natural sources. New powerful antibacterial agents can be produced by simply combining oils that are known for their antibacterial activities. In this study, apricot seed oil (ASO), date seed oil (DSO), grape seed oil (GSO), and black seed oil (BSO) alone and in binary mixtures were assessed. Fatty acid profiles of individual oils and oil mixtures showed linoleic acid, oleic acid, palmitic acid, stearic acid, and linolenic acid contents. Linoleic acid was the most abundant fatty acid in all samples except for ASO, where oleic acid was the dominant one. GSO showed the highest total phenolic content while ASO showed the lowest one. Antibacterial screening was performed against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Staphylococcus aureus. Results showed antibacterial activity in all oils against tested strains except for ASO against S. aureus. Highest antibacterial activity recorded was for ASO against P. mirabilis. ASO-GSO mixture (AG) was the best mixture where it showed synergistic interactions against all strains except P. aeruginosa. In conclusion, seed oil mixtures are likely to show promising antibacterial activities against specific strains.
Assuntos
Prunus armeniaca , Vitis , Ácido Linoleico , Staphylococcus aureus , Ácidos Graxos/farmacologia , Óleos de Plantas/farmacologia , Ácido Oleico/farmacologia , Antibacterianos/farmacologia , SementesRESUMO
The Selçuk district of Izmir is one of the most essential regions in terms of olive oil production. In this study, 60 olive oil samples were obtained from five different locations (ES: Eski Sirince Yolu, KK: Kinali Köprü, AU: Abu Hayat Üst, AA: Abu Hayat Alt, and DB: Degirmen Bogazi) in the Selçuk region of Izmir during two (2019-2020 and 2020-2021) consecutive cropping seasons. Quality indices (free acidity, peroxide value, p-Anisidine value, TOTOX, and spectral absorption at 232 and 270 nm) and the fatty acid, phenolic, and sterol profiles of the samples were determined to analyze the changes in the composition of Selcuk olive oils according to their growing areas. When the quality criteria were analyzed, it was observed that KK had the lowest FFA (0.11% oleic acid, PV (6.66 meq O2/kg), p-ANV (11.95 mmol/kg), TOTOX (25.28), and K232 (1.99) values and K270 had the highest value. During the assessment of phenolic profiles, the ES group exhibited the highest concentration of the phenolic compound p-HPEA-EDA (oleocanthal), with a content of 93.58 mg/kg, equivalent to tyrosol. Upon analyzing the fatty acid and sterol composition, it was noted that AU displayed the highest concentration of oleic acid (71.98%) and ß-sitosterol (87.65%). PCA analysis illustrated the distinct separation of the samples, revealing significant variations in both sterol and fatty acid methyl ester distributions among oils from different regions. Consequently, it was determined that VOOs originating from the Selçuk region exhibit distinct characteristics based on their geographical locations. Hence, this study holds great promise for the region to realize geographically labeled VOOs.
Assuntos
Olea , Ácido Oleico , Azeite de Oliva/análise , Ácidos Graxos , Peróxidos , Esteróis , Óleos de PlantasRESUMO
We investigated the effects of fatty acid/ monoglyceride type and amount on the absorption of fat-soluble vitamins. Micelles or vesicles made with either caprylic acid (CA) + monocaprylin (MC) or oleic acid (OA) + monoolein (MO) at low or high concentrations were infused in bile duct-ligated mice. Retinol + retinyl ester and γ-tocopherol intestinal mucosa contents were higher in mice infused with CA + MC than with OA + MO (up to + 350 % for vitamin A and up to + 62 %, for vitamin E; p < 0.05). Cholecalciferol intestinal mucosa content was the highest in mice infused with micelles with CA + MC at 5 mg/mL (up to + 105 %, p < 0.05). Retinyl ester plasma response was higher with mixed assemblies formed at low concentration of FA + MG compared to high concentration (up to + 1212 %, p < 0.05), while no difference in cholecalciferol and γ-tocopherol plasma responses were measured. No correlation between size or zeta potential and vitamin absorption was found. The impact of FA and MG on fat-soluble vitamin absorption thus differs from one vitamin to another and should be considered to formulate adequate vitamin oral or enteral supplements.
Assuntos
Caprilatos , Ácidos Graxos , Glicerídeos , Monoglicerídeos , Camundongos , Animais , Ácidos Graxos/farmacologia , gama-Tocoferol , Ésteres de Retinil/farmacologia , Micelas , Absorção Intestinal , Vitaminas , Vitamina A/metabolismo , Colecalciferol , Ácido OleicoRESUMO
This study aims to introduce a new liposome to co-load Antarctic krill oil (AKO) and quercetin (QC) as a new delivery formulation to enrich the application of AKO and QC. The stability of liposomes could be increased by adding an appropriate quantity of soy lecithin (SL). Changes in the composition of the phospholipid membrane were strongly correlated with the stability and release capacity of loaded nutrients. SL2@QC/AKO-lips displayed a nearly spherical shape with higher oxidative stability and controlled the in vitro release performance of QC in simulated digestion. Moreover, in vitro studies indicated that new liposomes had no adverse effects on cell viability and could combine the physiological functions of AKO and QC to protect the HepG2 cells from oleic acid-induced steatosis and oxidative stress. The findings demonstrated that the AKO and QC co-loaded liposomes prepared with the addition of an appropriate quantity of SL had excellent loading efficiency of AKO/QC and good oxidative stability, security and functional activity.
Assuntos
Euphausiacea , Lipossomos , Animais , Lipossomos/farmacologia , Quercetina/farmacologia , Ácido Oleico/farmacologia , Óleos/farmacologia , Estresse Oxidativo , LecitinasRESUMO
Very long-chain fatty acids (VLCFAs) are degraded exclusively in peroxisomes, as evidenced by the accumulation of VLCFAs in patients with certain peroxisomal disorders. Although accumulation of VLCFAs is considered to be associated with health issues, including neuronal degeneration, the mechanisms underlying VLCFAs-induced tissue degeneration remain unclear. Here, we report the toxic effect of VLCFA and protective effect of C18: 1 FA in peroxisome-deficient CHO cells. We examined the cytotoxicity of saturated and monounsaturated VLCFAs with chain-length at C20-C26, and found that longer and saturated VLCFA showed potent cytotoxicity at lower accumulation levels. Furthermore, the extent of VLCFA-induced toxicity was found to be associated with a decrease in cellular C18:1 FA levels. Notably, supplementation with C18:1 FA effectively rescued the cells from VLCFA-induced apoptosis without reducing the cellular VLCFAs levels, implying that peroxisome-deficient cells can survive in the presence of accumulated VLCFA, as long as the cells keep sufficient levels of cellular C18:1 FA. These results suggest a therapeutic potential of C18:1 FA in peroxisome disease and may provide new insights into the pharmacological effect of Lorenzo's oil, a 4:1 mixture of C18:1 and C22:1 FA.
Assuntos
Ácido Oleico , Peroxissomos , Animais , Cricetinae , Humanos , Ácido Oleico/farmacologia , Ácido Oleico/metabolismo , Peroxissomos/metabolismo , Ácidos Graxos/metabolismo , Cricetulus , Células CHO , Ácidos Graxos não Esterificados/metabolismo , ApoptoseRESUMO
Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD via gut microbiota-dependent AA metabolism. These results highlight the need for reducing oral exposure to synthetic preservatives to improve metabolic disturbance under HFD conditions.
Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/metabolismo , Metabolismo dos Lipídeos , Parabenos/toxicidade , Dieta Hiperlipídica/efeitos adversos , Ácido Oleico/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Skeletal muscle is one of the largest metabolic tissues in mammals and is composed of four different types of muscle fibers (types 1, 2A, 2X, and 2B); however, type 2B is absent in humans. Given that slow-twitch fibers are superior to fast-twitch fibers in terms of oxidative metabolism and are rich in mitochondria, shift of muscle fiber types in direction towards slower fiber types improves metabolic disorders and endurance capacity. We previously had reported that oleic acid supplementation increases type 1 fiber formation in C2C12 myotubes; however, its function still remains unclear. This study aimed to determine the effect of oleic acid on the muscle fiber types and endurance capacity. An in vivo mouse model was used, and mice were fed a 10% oleic acid diet for 4 weeks. Two different skeletal muscles, slow soleus muscle with the predominance of slow-twitch fibers and fast extensor digitorum longus (EDL) muscle with the predominance of fast-twitch fibers, were used. We found that dietary oleic acid intake improved running endurance and altered fiber type composition of muscles, the proportion of type 1 and 2X fibers increased in the soleus muscle and type 2X increased in the EDL muscle. The fiber type shift in the EDL muscle was accompanied by an increased muscle TAG content. In addition, blood triacylglycerol (TAG) and non-esterified fatty acid levels decreased during exercise. These changes suggested that lipid utilization as an energy substrate was enhanced by oleic acid. Increased proliferator-activated receptor γ coactivator-1ß protein levels were observed in the EDL muscle, which potentially enhanced the fiber type transitions towards type 2X and muscle TAG content. In conclusion, dietary oleic acid intake improved running endurance with the changes of muscle fiber type shares in mice. This study elucidated a novel functionality of oleic acid in skeletal muscle fiber types. Further studies are required to elucidate the underlying mechanisms. Our findings have the potential to contribute to the field of health and sports science through nutritional approaches, such as the development of supplements aimed at improving muscle function.
Assuntos
Fibras Musculares Esqueléticas , Ácido Oleico , Humanos , Animais , Camundongos , Ácido Oleico/farmacologia , Músculo Esquelético , Respiração Celular , Suplementos Nutricionais , MamíferosRESUMO
The emergence and spread of antimalarial drug resistance have become a significant problem worldwide. The search for natural products to develop novel antimalarial drugs is challenging. Therefore, this study aimed to assess the antimalarial and toxicological effects of Chan-Ta-Lee-La (CTLL) and Pra-Sa-Chan-Dang (PSCD) formulations and their plant ingredients. The crude extracts of CTLL and PSCD formulations and their plant ingredients were evaluated for in vitro antimalarial activity using Plasmodium lactate dehydrogenase enzyme and toxicity to Vero and HepG2 cells using the tetrazolium salt method. An extract from the CTLL and PSCD formulations exhibiting the highest selectivity index value was selected for further investigation using Peter's 4-day suppressive test, curative test, prophylactic test, and acute oral toxicity in mice. The phytochemical constituents were characterized using gas chromatography-mass spectrometry (GC-MS). Results showed that ethanolic extracts of CTLL and PSCD formulations possessed high antimalarial activity (half maximal inhibitory concentration = 4.88, and 4.19 g/mL, respectively) with low cytotoxicity. Ethanolic extracts of the CTLL and PSCD formulations demonstrated a significant dose-dependent decrease in parasitemia in mice. The ethanolic CTLL extract showed the greatest suppressive effect after 4 days of suppressive (89.80%) and curative (35.94%) testing at a dose of 600 mg/kg. Moreover, ethanolic PSCD extract showed the highest suppressive effect in the prophylactic test (65.82%) at a dose of 600 mg/kg. There was no acute toxicity in mice treated with ethanolic CTLL and PSCD extracts at 2,000 mg/kg bodyweight. GC-MS analysis revealed that the most abundant compounds in the ethanolic CTLL extract were linderol, isoborneol, eudesmol, linoleic acid, and oleic acid, whereas ethyl 4-methoxycinnamate was the most commonly found compound in the ethanolic PSCD extract, followed by 3-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-4H-chromen-4-one, flamenol, oleic acid amide, linoleic acid, and oleic acid. In conclusions, ethanolic CTLL and PSCD extracts exhibited high antimalarial efficacy in vitro. The ethanolic CTLL extract at a dose of 600 mg/kg exhibited the highest antimalarial activity in the 4-day suppressive and curative tests, whereas the ethanolic PSCD extract at a dose of 600 mg/kg showed the highest antimalarial activity in the prophylactic test.
Assuntos
Antimaláricos , Malária , Animais , Camundongos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Antimaláricos/química , Ácido Linoleico , Ácido Oleico/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Malária/tratamento farmacológico , Misturas Complexas/farmacologia , Plasmodium bergheiRESUMO
The concept that fat supplementation impairs total-tract fiber digestibility in ruminants has been widely accepted over the past decades. Nevertheless, the recent interest in the dietary fatty acid profile to dairy cows enlightened the possible beneficial effect of specific fatty acids (e.g., palmitic, stearic, and oleic acids) on total-tract fiber digestibility. Because palmitic, stearic, and oleic acids are the main fatty acids present in ruminal bacterial cells, we hypothesize that the dietary supply of these fatty acids will favor their incorporation into the bacterial cell membranes, which will support the growth and enrichment of fiber-digesting bacteria in the rumen. Our objective in this experiment was to investigate how dietary supply of palmitic, stearic, and oleic acid affect fiber digestion, bacterial membrane fatty acid profile, microbial growth, and composition of the rumen bacterial community. Diets were randomly assigned to 8 single-flow continuous culture fermenters arranged in a replicated 4 × 4 Latin square with four 11-d experimental periods. Treatments were (1) a control basal diet without supplemental fatty acids (CON); (2) the control diet plus palmitic acid (PA); (3) the control diet plus stearic acid (SA); and (4) the control diet plus oleic acid (OA). All fatty acid treatments were included in the diet at 1.5% of the diet (dry matter [DM] basis). The basal diet contained 50% orchardgrass hay and 50% concentrate (DM basis) and was supplied at a rate of 60 g of DM/d in 2 equal daily offers (0800 and 1600 h). Data were analyzed using a mixed model considering treatments as fixed effect and period and fermenter as random effects. Our results indicate that PA increased in vitro fiber digestibility by 6 percentage units compared with the CON, while SA had no effect and OA decreased fiber digestibility by 8 percentage units. Oleic acid decreased protein expression of the enzymes acetyl-CoA carboxylase compared with CON and PA, while fatty acid synthase was reduced by PA, SA, and OA. We observed that PA, but not SA or OA, altered the bacterial community composition by enhancing bacterial groups responsible for fiber digestion. Although the dietary fatty acids did not affect the total lipid content and the phospholipid fraction in the bacterial cell, PA increased the flow of anteiso C13:0 and anteiso C15:0 in the phospholipidic membrane compared to the other treatments. In addition, OA increased the flow of C18:1 cis-9 and decreased C18:2 cis-9,cis-12 in the bacterial phospholipidic membranes compared to the other treatments. Palmitic acid tended to increase bacterial growth compared to other treatments, whereas SA and OA did not affect bacterial growth compared with CON. To our knowledge, this is the first research providing evidence that palmitic acid supports ruminal fiber digestion through shifts in bacterial fatty acid metabolism that result in changes in growth and abundance of fiber-degrading bacteria in the microbial community.
Assuntos
Suplementos Nutricionais , Ácido Oleico , Bovinos , Feminino , Animais , Ácido Oleico/metabolismo , Leite/metabolismo , Lactação , Rúmen/metabolismo , Digestão , Ácidos Graxos/metabolismo , Dieta/veterinária , Ácido Palmítico/metabolismoRESUMO
Hippophae rhamnoides exhibit a wide variety of medicinal and pharmacological effects. The present study aims to determine the role of ethanol extract of H. rhamnoides on oleic acid (OA)-induced acute respiratory distress syndrome (ARDS) in rats. Male rats were randomly divided into the following groups: (I) Control, (II) OA, and (III) OA+H. rhamnoides. H. rhamnoides extract (500 mg/kg) was given orally for 2 weeks before OA in Group III. Levels of total antioxidant capacity, total oxidant status (TOS), myeloperoxidase (MPO), mitogen-activated protein kinase (MAPK), acetylcholinesterase (AChE), and angiotensin-converting enzyme (ACE) were quantified by enzyme-linked immunosorbent assay (ELISA). Real time quantitative polymerase chain reaction was utilized to evaluate the expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and matrix metalloproteinase 2 (MMP2). Also, Caspase-3 immunostaining and expression were performed to evaluate apoptosis. Compared with the OA group, there was a significantly decrease in the levels of MPO, TOS, MAPK, and ACE and in the expression of NF-κB, TNF-α, IL-6, MMP2, and Caspase-3 in the H. rhamnoides administration group. Moreover, the activity of AChE and level of TAS were substantially higher in the H. rhamnoides administration compared with the OA group. The findings in the study suggest that the protective effect of H. rhamnoides pretreatment may act through inhibition of the ACE activity, releasing AChE, regulation of inflammatory cytokine levels, and suppression of apoptotic process in ARDS.
Assuntos
Hippophae , Síndrome do Desconforto Respiratório , Ratos , Masculino , Animais , NF-kappa B/metabolismo , Metaloproteinase 2 da Matriz , Acetilcolinesterase , Ácido Oleico , Hippophae/metabolismo , Caspase 3 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Interleucina-6/genética , AngiotensinasRESUMO
The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. This disease encompasses several stages, from steatosis to steatohepatitis and, eventually, to fibrosis and cirrhosis. Exposure to environmental contaminants is one of the risk factors and an increasing amount of evidence points to a role for endocrine disrupting compounds (EDCs). This study assesses the impact of selected EDCs on the formation of lipid droplets, the marker for steatosis in a hepatic model. The mechanisms underlying this effect are then explored. Ten compounds were selected according to their obesogenic properties: bisphenol A, F and S, butyl-paraben, cadmium chloride, p,p'-DDE, DBP, DEHP, PFOA and PFOS. Using a 2D or 3D model, HepaRG cells were exposed to the compounds with or without fatty acid supplementation. Then, the formation of lipid droplets was quantified by an automated fluorescence-based method. The expression of genes and proteins involved in lipid metabolism and the impact on cellular respiration was analyzed. The formation of lipid droplets, which is revealed or enhanced by oleic acid supplementation, was most effectively induced by p,p'-DDE and DEHP. Experiments employing either 2D or 3D culture conditions gave similar results. Both compounds induced the expression of PLIN2. p,p'-DDE also appears to act by decreasing in fatty acid oxidation. Some EDCs were able to induce the formation of lipid droplets, in HepaRG cells, an effect which was increased after supplementation of the cells with oleic acid. A full understanding of the mechanisms of these effects will require further investigation. The novel automated detection method described here may also be useful in the future as a regulatory test for EDC risk assessment.
Assuntos
Dietilexilftalato , Disruptores Endócrinos , Fígado Gorduroso , Humanos , Metabolismo dos Lipídeos , Ácidos Graxos/metabolismo , Disruptores Endócrinos/metabolismo , Ácido Oleico/toxicidade , Ácido Oleico/metabolismo , Diclorodifenil Dicloroetileno/metabolismo , Dietilexilftalato/toxicidade , Fígado Gorduroso/metabolismo , HepatócitosRESUMO
Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies that can be influenced by Fusobacterium nucleatum (Fn), a bacterium that promotes tumor development and chemoresistance, resulting in limited therapeutic efficacy. Traditional antibiotics cannot effectively eliminate Fn at tumor site due to issues like biofilm formation, while chemotherapy alone fails to suppress tumor progression. Therefore, the development of new methods to eliminate Fn and promote antitumor efficacy is of great significance for improving the outcome of CRC treatment. Herein, we developed a nanodrug (OPPL) that integrates oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) and an amphiphilic polymer (PPL) to deliver the platinum prodrug and antimicrobial lauric acid (LA) for enhancing the treatment of CRC. We demonstrated that OPPL can synergistically enhance antibacterial and biofilm disruption activities against Fn along with the antimicrobial LA by producing reactive oxygen species (ROS) through its peroxidase-like activity. Furthermore, the OPPL nanodrug can increase intracellular ROS, promote lipid peroxides and deplete glutathione, leading to ferroptosis. By combining chemotherapy and induced ferroptosis, the OPPL nanodrug exhibited high cytotoxicity against CRC cells. In vivo studies showed that the OPPL nanodrug could enhance tumor accumulation, enable magnetic resonance imaging, suppresse tumor growth, and inhibit growth of intratumor Fn. These results suggest that OPPL is an effective and promising candidate for the treatment of Fn-infected CRC. STATEMENT OF SIGNIFICANCE: The enrichment of Fusobacterium nucleatum (Fn) in colorectal cancer is reported to exacerbate tumor malignancy and is particularly responsible for chemoresistance. To this respect, we strategically elaborated multifaceted therapeutics, namely OPPL nanodrug, combining oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) with a polymer containing a platinum prodrug and antimicrobial lauric acid. The O-SPION components exert distinctive peroxidase-like activity, capable of stimulating Fenton reactions selectively in the tumor microenvironment, consequently accounting for the progressive production of reactive oxygen species. Hence, O-SPIONs have been demonstrated to not only supplement the antimicrobial activities of lauric acid in overcoming Fn-induced chemoresistance but also stimulate potent tumor ferroptosis. Our proposed dual antimicrobial and chemotherapeutic nanodrug provides an appreciable strategy for managing challenging Fn-infected colorectal cancer.
Assuntos
Anti-Infecciosos , Neoplasias Colorretais , Pró-Fármacos , Humanos , Espécies Reativas de Oxigênio , Ácido Oleico , Platina , Fusobacterium nucleatum , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Polímeros , Nanopartículas Magnéticas de Óxido de Ferro , Antibacterianos/farmacologia , Peroxidases , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) involves hepatic accumulation of intracellular lipid droplets via incompletely understood processes. Here, we report distinct and cooperative NAFLD roles of LysTTT-5'tRF transfer RNA fragments and microRNA miR-194-5p. METHODS: Combined use of diet induced obese mice with human-derived oleic acid-exposed Hep G2 cells revealed new NAFLD roles of LysTTT-5'tRF and miR-194-5p. RESULTS: Unlike lean animals, dietary-induced NAFLD mice showed concurrent hepatic decrease of both LysTTT-5'tRF and miR-194-5p levels, which were restored following miR-132 antisense oligonucleotide treatment which suppresses hepatic steatosis. Moreover, exposing human-derived Hep G2 cells to oleic acid for 7 days co-suppressed miR-194-5p and LysTTT-5'tRF levels while increasing lipid accumulation. Inversely, transfecting fattened cells with a synthetic LysTTT-5'tRF mimic elevated mRNA levels of the metabolic regulator ß-Klotho while decreasing triglyceride amounts by 30% within 24 h. In contradistinction, antisense suppression of miR-194-5p induced accumulation of its novel target, the NAFLD-implicated lipid droplet-coating PLIN2 protein. Further, two out of 15 steatosis-alleviating screened drug-repurposing compounds, Danazol and Latanoprost, elevated miR-194-5p or LysTTT-5'tRF levels. CONCLUSION: Our findings highlight the different yet complementary roles of miR-194-5p and LysTTT-5'tRF and offer new insights into the complex roles of small non-coding RNAs and the multiple pathways involved in NAFLD pathogenesis.
Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Lisina , MicroRNAs/genética , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico , Perilipina-2RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: A combination of 6 different Chinese herbs known as Erchen decoction (ECD) has been traditionally used to treat digestive tract diseases and found to have a protective effect against nonalcoholic fatty liver disease (NAFLD). Despite its efficacy in treating NAFLD, the precise molecular mechanism by which Erchen Decoction regulated iron ion metabolism to prevent disease progression remained poorly understood. AIM OF STUDY: Our study attempted to confirm the specific mechanism of ECD in reducing lipid and iron in NAFLD from the perspective of regulating the expression of Caveolin-1 (Cav-1). STUDY DESIGN: In our study, the protective effect of ECD was investigated in Palmitic Acid + Oleic Acid-induced hepatocyte NAFLD model and high-fat diet-induced mice NAFLD model. To investigate the impact of Erchen Decoction (ECD) on lipid metabolism and iron metabolism via mediating Cav-1 in vitro, Cav-1 knockdown cell lines were established using lentivirus-mediated transfection techniques. MATERIALS AND METHODS: We constructed NAFLD model by feeding with high-fat diet for 12 weeks in vivo and Palmitic Acid + Oleic Acid treatment for 24 h in vitro. The regulation of Lipid and iron metabolism results by ECD were detected by serological diagnosis, immunofluorescent and immunohistochemical staining, and western blotting. The binding ability of 6 small molecules of ECD to Cav-1 was analyzed by molecular docking. RESULTS: We demonstrated that ECD alleviated the progression of NAFLD by inhibiting lipid accumulation, nitrogen oxygen stress, and iron accumulation in vivo and in vitro experiments. Furthermore, ECD inhibited lipid and iron accumulation in liver by up-regulating the expression of Cav-1, which indicated that Cav-1 was an important target for ECD to exert its curative effect. CONCLUSIONS: In summary, our study demonstrated that ECD alleviated the accumulation of lipid and iron in NAFLD through promoting the expression of Cav-1, and ECD might serve as a novel Cav-1 agonist to treat NAFLD.
Assuntos
Sobrecarga de Ferro , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Palmítico/toxicidade , Caveolina 1/genética , Ácido Oleico/farmacologia , Simulação de Acoplamento Molecular , Fígado , Metabolismo dos Lipídeos , Sobrecarga de Ferro/tratamento farmacológico , Ferro/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BLRESUMO
Edible oils with high unsaturated fatty acids, particularly oleic acid, are beneficial to human health. Cotton is one of the top five oil crops in the world, but the mechanism of high-quality oil synthesis and regulatory networks in cotton are largely unclear. Here, we identified Leafy cotyledon1-like 1 (GhL1L1), a NF-YB subfamily gene that is specifically expressed during somatic embryogenesis and seed maturation in cotton. Overexpression of GhL1L1 regulates the contents of unsaturated fatty acids in cotton, especially in the seeds, which is associated with altered expression of the cotton fatty acid biosynthesis-related genes. GhL1L1 synergistically enhanced the expression of GhFAD2-1A by binding to the G-box in its promoter, leading to an increase in the content of linoleic acid. Furthermore, this activation could be enhanced by GhNF-YC2 and GhNF-YA1 by form a transcriptional complex. Collectively, these results contribute to provide new insights into the molecular mechanism of oil biosynthesis in cotton and can facilitate genetic manipulation of cotton varieties with enhanced oil content.
Assuntos
Ácidos Graxos Insaturados , Proteínas de Plantas , Humanos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácidos Graxos Insaturados/genética , Ácidos Graxos Insaturados/metabolismo , Ácido Oleico/metabolismo , Ácido Linoleico , Sementes/genética , Sementes/metabolismo , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Óleos de Plantas , Regulação da Expressão Gênica de PlantasRESUMO
Protein-bound Nε-(carboxymethyl)lysine (CML), an advanced glycation end product within meat products, poses a potential health risk to humans. The objective of this study was to explore the impact of various edible oils on the formation of protein-bound CML in roasted pork patties. Eleven commercially edible oils including lard oil, corn oil, palm oil, olive oil, flaxseed oil, blended oil, camellia oil, walnut oil, soybean oil, peanut oil, and colza oil were added to pork tenderloin mince, respectively, at a proportion of 4 % to prepare raw pork patties. The protein-bound CML contents in the pork patties were determined by HPLC-MS/MS before and after roasting at 200 °C for 20 min. The results indicated that walnut oil, flaxseed oil, colza oil, olive oil, lard oil, corn oil, blended oil, and palm oil significantly reduced the accumulation of protein-bound CML in pork patties, of which the inhibition rate was in the 24.43 %-37.96 % range. Moreover, the addition of edible oil contributed to a marginal reduction in the loss of lysine. Meanwhile, glyoxal contents in pork patties were reduced by 16.72 %-43.21 % after roasting. Other than blend oil, all the other edible oils restrained protein oxidation in pork patties to varying degrees (between 20.16 % and 61.26 %). In addition, camellia oil, walnut oil, and flaxseed oil increased TBARS values of pork patties by 2.2-8.6 times when compared to the CON group. After analyzing the fatty acid compositions of eleven edible oils, five main fatty acids (palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid) were selected to establish Myofibrillar protein-Glucose-fatty acids systems to simulate the roasting process. The results showed that palmitic acid, oleic acid, linoleic acid, and linolenic acid obviously mitigated the formation of myofibrillar protein-bound CML, exhibiting suppression rates ranging from 10.38 % to 40.32 %. In conclusion, the addition of specific edible oil may curb protein-bound CML production in roasted pork patty by restraining protein or lipid oxidation, reducing lysine loss, and suppressing glyoxal production, which may be attributed to the fatty acid compositions of edible oils. This finding provides valuable guidance for the selection of healthy roasting oils in the thermal processing of meat products.
Assuntos
Carne de Porco , Carne Vermelha , Animais , Humanos , Suínos , Azeite de Oliva , Óleo de Semente do Linho , Lisina , Óleo de Milho , Espectrometria de Massas em Tandem , Óleos de Plantas , Ácido Linoleico , Ácido Palmítico , Ácido Oleico , Glioxal , Ácidos LinolênicosRESUMO
Acylethanolamides (NAEs) are bioactive lipids derived from diet fatty acids that modulate important homeostatic functions, including appetite, fatty acid synthesis, mitochondrial respiration, inflammation, and nociception. Among the naturally circulating NAEs, the pharmacology of those derived from either arachidonic acid (Anandamide), oleic acid (OEA), and palmitic acid (PEA) have been extensively characterized in diet-induced obesity. For the present work, we extended those studies to linoleoylethanolamide (LEA), one of the most abundant NAEs found not only in plasma and body tissues but also in foods such as cereals. In our initial study, circulating concentrations of LEA were found to be elevated in overweight humans (body mass index (BMI, Kg/m2) > 25) recruited from a representative population from the south of Spain, together with AEA and the endocannabinoid 2-Arachidonoyl glycerol (2-AG). In this population, LEA concentrations correlated with the circulating levels of cholesterol and triglycerides. In order to gain insight into the pharmacology of LEA, we administered it for 14 days (10 mg/kg i.p. daily) to obese male Sprague Dawley rats receiving a cafeteria diet or a standard chow diet for 12 consecutive weeks. LEA treatment resulted in weight loss and a reduction in circulating triglycerides, cholesterol, and inflammatory markers such as Il-6 and Tnf-alpha. In addition, LEA reduced plasma transaminases and enhanced acetyl-CoA-oxidase (Acox) and Uncoupling protein-2 (Ucp2) expression in the liver of the HFD-fed animals. Although the liver steatosis induced by the HFD was not reversed by LEA, the overall data suggest that LEA contributes to the homeostatic signals set in place in response to diet-induced obesity, potentially contributing with OEA to improve lipid metabolism after high fat intake. The anti-inflammatory response associated with its administration suggests its potential for use as a nutrient supplement in non-alcoholic steatohepatitis.