RESUMO
Chronic inflammation is a fundamental aspect of metabolic disorders such as obesity, diabetes and cardiovascular disease. Cholesterol crystals are metabolic signals that trigger sterile inflammation in atherosclerosis, presumably by activating inflammasomes for IL-1ß production. We found here that atherogenesis was mediated by IL-1α and we identified fatty acids as potent inducers of IL-1α-driven vascular inflammation. Fatty acids selectively stimulated the release of IL-1α but not of IL-1ß by uncoupling mitochondrial respiration. Fatty acid-induced mitochondrial uncoupling abrogated IL-1ß secretion, which deviated the cholesterol crystal-elicited response toward selective production of IL-1α. Our findings delineate a previously unknown pathway for vascular immunopathology that links the cellular response to metabolic stress with innate inflammation, and suggest that IL-1α, not IL-1ß, should be targeted in patients with cardiovascular disease.
Assuntos
Aterosclerose/metabolismo , Ácidos Graxos/metabolismo , Inflamassomos/metabolismo , Interleucina-1alfa/metabolismo , Mitocôndrias/metabolismo , Vasculite/metabolismo , Animais , Aterosclerose/genética , Aterosclerose/patologia , Sinalização do Cálcio , Gorduras na Dieta/metabolismo , Ácidos Graxos/farmacologia , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Canais Iônicos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Ácido Oleico/farmacologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Proteína Desacopladora 2 , Vasculite/patologiaRESUMO
Fatty acids are an important source of energy and a key component of phospholipids in membranes and organelles. Saturated fatty acids (SFAs) are converted into unsaturated fatty acids (UFAs) by stearoyl Co-A desaturase (SCD), an enzyme active in cancer. Here, we studied how the dynamics between SFAs and UFAs regulated by SCD impacts ovarian cancer cell survival and tumor progression. SCD depletion or inhibition caused lower levels of UFAs vs. SFAs and altered fatty acyl chain plasticity, as demonstrated by lipidomics and stimulated Raman scattering (SRS) microscopy. Further, increased levels of SFAs resulting from SCD knockdown triggered endoplasmic reticulum (ER) stress response with brisk activation of IRE1α/XBP1 and PERK/eIF2α/ATF4 axes. Disorganized ER membrane was visualized by electron microscopy and SRS imaging in ovarian cancer cells in which SCD was knocked down. The induction of long-term mild ER stress or short-time severe ER stress by the increased levels of SFAs and loss of UFAs led to cell death. However, ER stress and apoptosis could be readily rescued by supplementation with UFAs and reequilibration of SFA/UFA levels. The effects of SCD knockdown or inhibition observed in vitro translated into suppression of intraperitoneal tumor growth in ovarian cancer xenograft models. Furthermore, a combined intervention using an SCD inhibitor and an SFA-enriched diet initiated ER stress in tumors growing in vivo and potently blocked their dissemination. In all, our data support SCD as a key regulator of the cancer cell fate under metabolic stress and point to treatment strategies targeting the lipid balance.
Assuntos
Sobrevivência Celular , Endorribonucleases , Ácidos Graxos Insaturados , Neoplasias Ovarianas , Progressão da Doença , Ácidos Graxos Dessaturases , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Feminino , Humanos , Fosfolipídeos , Proteínas Serina-Treonina Quinases , Estearoil-CoA Dessaturase/metabolismoRESUMO
Medium-chain fatty acids (MCFAs) have 6-12 carbon atoms and are instantly absorbed into the bloodstream before traveling to the portal vein and the liver, where they are immediately used for energy and may have antitumor effects. Its role in breast cancer is poorly understood. To investigate the apoptosis-inducing effect of MCFAs in breast cancer cells, cell viability assay, colony formation assay, cell migration assay, cell invasion assay, nuclear morphology, cell cycle assay, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), apoptosis, RT-qPCR analysis, and Western blot analysis were performed. In the present study, MCFA treatments reduced proliferative capability, increased ROS level, increased the depletion of MMP, induced G0/G1 and S phase cell cycle arrest, and late apoptosis of breast cancer cells in an effective concentration. Besides, MCFA treatment contributed to the upregulation of proapoptotic protein (BAK) and caspase-3, and the downregulation of antiapoptotic protein (Bcl-2). Mechanistically, phosphorylation levels of EGFR, Akt, and mTOR were significantly reduced in breast cancer cells treated with MCFAs. However, no significant changes in apoptosis and signaling-related proteins were observed in lauric acid-treated ER-positive cancer cells. Our findings suggested that MCFAs suppressed breast cancer cell proliferation by modulating the PI3K/Akt/mTOR signaling pathway. MCFAs may be a promising therapeutic drug for treating breast cancer.
Assuntos
Apoptose , Neoplasias da Mama , Proliferação de Células , Ácidos Graxos , Proteínas Proto-Oncogênicas c-bcl-2 , Transdução de Sinais , Feminino , Humanos , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células MCF-7 , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
A growing appreciation of the importance of cellular metabolism and revelations concerning the extent of cell-cell heterogeneity demand metabolic characterization of individual cells. We present SpaceM, an open-source method for in situ single-cell metabolomics that detects >100 metabolites from >1,000 individual cells per hour, together with a fluorescence-based readout and retention of morpho-spatial features. We validated SpaceM by predicting the cell types of cocultured human epithelial cells and mouse fibroblasts. We used SpaceM to show that stimulating human hepatocytes with fatty acids leads to the emergence of two coexisting subpopulations outlined by distinct cellular metabolic states. Inducing inflammation with the cytokine interleukin-17A perturbs the balance of these states in a process dependent on NF-κB signaling. The metabolic state markers were reproduced in a murine model of nonalcoholic steatohepatitis. We anticipate SpaceM to be broadly applicable for investigations of diverse cellular models and to democratize single-cell metabolomics.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Metabolômica/métodos , Análise de Célula Única/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Técnicas de Cocultura , Células Epiteliais , Ácidos Graxos/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-17/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Células NIH 3T3 , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Transdução de Sinais , Estresse FisiológicoRESUMO
In this issue of Immunity, Haghikia and colleagues (2015) demonstrate that dietary fatty acids, by modulating gut microbes and their metabolism, regulate mucosal immune cells to impact systemic immunity. Using this mechanism, dietary and bacteria-derived medium-chain and long-chain fatty acids exacerbate, whereas short-chain fatty acids ameliorate, autoimmunity in the brain.
Assuntos
Autoimunidade/efeitos dos fármacos , Sistema Nervoso Central/imunologia , Gorduras na Dieta/farmacologia , Duodeno/imunologia , Encefalomielite Autoimune Experimental/etiologia , Ácidos Graxos/farmacologia , Linfopoese/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , AnimaisRESUMO
Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis.
Assuntos
Autoimunidade/efeitos dos fármacos , Sistema Nervoso Central/imunologia , Gorduras na Dieta/farmacologia , Duodeno/imunologia , Encefalomielite Autoimune Experimental/etiologia , Ácidos Graxos/farmacologia , Linfopoese/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , Animais , Gorduras na Dieta/toxicidade , Duodeno/metabolismo , Duodeno/microbiologia , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Ácidos Graxos/química , Ácidos Graxos/toxicidade , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Regulação da Expressão Gênica/imunologia , Ácidos Láuricos/toxicidade , Receptores X do Fígado , Sistema de Sinalização das MAP Quinases , Camundongos , Peso Molecular , Receptores Nucleares Órfãos/biossíntese , Receptores Nucleares Órfãos/genética , Receptores Acoplados a Proteínas G/biossíntese , Receptores Acoplados a Proteínas G/genética , Baço/imunologia , Baço/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , TranscriptomaRESUMO
Neuroblastoma and glioblastoma are the most commonly seen nervous system tumors, and their treatment is challenging. Relatively safe and easy acquisition of nutraceutical natural products make them suitable candidates for anticancer research. Royal jelly (RJ), a superfood, has many biological and pharmacological activities. This study was conducted to, for the first time, elucidate its anticancer efficiency, even in high doses, on neuroblastoma and glioblastoma cell lines through cell viability, apoptosis, cell cycle and biomolecular content evaluation. We performed experiments with RJ concentrations in the range of 1.25-10 mg mL-1 for 48 h. Cell viability assays revealed a notable cytotoxic effect of RJ in a concentration-dependent manner. Treatment with a high dose of RJ significantly increased the apoptotic cell population of both cell lines. Furthermore, we observed G0-G1 phase arrest in neuroblastoma cells but G2-M arrest in glioblastoma cells. All these cellular changes are closely associated with the alterations of the macromolecular makeup of the cells, such as decreased saturated lipid, protein, DNA and RNA amounts, protein conformational changes, decreased protein phosphorylation and increased protein carbonylation. These cellular changes are associated with RJ triggered-ROS formation. The clear segregation between the control and the RJ-treated groups proved these changes, obtained from the unsupervised and supervised chemometric analysis. RJ has good anticancer activity against nervous system cancers and could be safely used with current treatment strategies.
Assuntos
Glioblastoma , Neuroblastoma , Humanos , Apoptose , Glioblastoma/tratamento farmacológico , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular , Ácidos Graxos/farmacologia , Proliferação de Células , Neuroblastoma/tratamento farmacológicoRESUMO
Ceramides, crucial sphingolipids in cellular biology, play various roles ranging from structural membrane integrity to signaling pathway regulation. Structurally, a ceramide consists of a fatty acid connected to a sphingoid base. The characteristics of the fatty acid chain, including length and saturation, determine the physiological properties of the ceramide. Ceramides typically fall into the following categories based on chain length: medium, long, very-long, and ultra-long. Among them, two very-long-chain ceramides, Cer(24:1(15Z)) and Cer(24:0), have been extensively studied, and they are known for their regulatory functions. However, the hydrophobic natures of ceramides, arising from their long hydrocarbon chain impedes their solubilities and levels of cellular delivery. Although ω-pyridinium ceramide analogs (ω-PyrCers) have been developed to address this issue, ω-PyrCers with very-long fatty acid chains or unsaturation have not been developed, presumably due to limited access to the corresponding ω-bromo fatty acids required in their syntheses. In this study, we prepared the ω-PyrCers of Cer(24:1(15Z)) and Cer(24:0), PyrCer(24:1(15Z)) and PyrCer(24:0), respectively. The key in the synthesis is the Wittig reaction to prepare the ω-bromo fatty acid with an appropriate chain length and (Z)-double bond position. Preliminary evaluation of the PyrCer(24:1(15Z)) and PyrCer(24:0) revealed their potential in hepatocellular carcinoma treatment.
Assuntos
Antineoplásicos , Ceramidas , Esfingolipídeos , Ceramidas/farmacologia , Ceramidas/química , Ácidos Graxos/farmacologia , Compostos de Piridínio/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológicoRESUMO
Oncorhynchus mykiss, a significant aquaculture species, possesses compounds with numerous biological and pharmacological functions, including antioxidant, anticancer, anti-microbial, and anti-obesity effects. However, possible anti-inflammatory effects of lipids extracted from O. mykiss eggs on RAW264.7 cells induced by LPS have not been elucidated yet. The current study identified 13 fatty acids in lipids extracted from O. mykiss eggs that contained high amounts (51.92% of total fatty acids) of polyunsaturated fatty acids (PUFAs), especially DHA (33.66%) and EPA (7.77%). These O. mykiss lipids (100-400 µg/mL) showed significant anti-inflammatory effects by inhibiting NO and iNOS expression in LPS-stimulated RAW264.7 cells. They also inhibited expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α, while upregulating anti-inflammatory cytokines IL-10, IL-11, and TGF-ß. These lipids from O. mykiss effectively inhibited LPS-induced expression CD86 as a surface biomarker on RAW264.7 cells. Additionally, O. mykiss lipids suppressed phosphorylation of p38, JNK, and ERK1/2 and the expression of phosphorylated NF-κB subunit p65. These findings indicate that O. mykiss lipids possess anti-inflammatory properties by inhibiting NF-κB and MAPK signaling pathways.
Assuntos
Ácidos Graxos , Oncorhynchus mykiss , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Citocinas/genética , Citocinas/metabolismo , Ácidos Graxos/farmacologia , Inflamação/tratamento farmacológico , Lipopolissacarídeos , NF-kappa B/genética , NF-kappa B/metabolismo , Oncorhynchus mykiss/metabolismo , Células RAW 264.7RESUMO
PURPOSE: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo. METHODS: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed. RESULTS: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured. CONCLUSION: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.
Assuntos
Células Endoteliais , Ácidos Graxos , Adulto , Humanos , Pessoa de Meia-Idade , Células Endoteliais/metabolismo , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados , Dieta , Laticínios , Período Pós-Prandial , Gorduras na Dieta/metabolismo , Estudos Cross-OverRESUMO
AIMS: This study aimed to investigate the changes of cell membrane structure and function of Issatchenkia terricola under citric acid by performing physiological analysis. METHODS AND RESULTS: The membrane integrity, surface hydrophobicity, structure, fluidity, apoptosis, and fatty acid methyl esters composition of I. terricola WJL-G4 cells were determined by propidium iodide staining, microbial adhesion to hydrocarbon test, transmission electron microscopy analysis, fluorescence anisotropy, flow cytometry, and gas chromatography-mass, respectively. The results showed that with the increasing of citric acid concentrations, the cell vitality, membrane integrity, and fluidity of I. terricola reduced; meanwhile, apoptosis rate, membrane permeable, hydrophobicity, and ergosterol contents augmented significantly. Compared to control, the activities of Na+, K+-ATPase, and Ca2+, Mg2+-ATPase increased by 3.73-fold and 6.70-fold, respectively, when citric acid concentration increased to 20 g l-1. The cells cracked and their cytoplasm effused when the citric acid concentration reached 80 g l-1. CONCLUSIONS: I. terricola could successfully adjust its membrane structure and function below 60 g l-1 of citric acid. However, for citric acid concentrations above 80 g l-1, its structure and function were dramatically changed, which might result in reduced functionality.
Assuntos
Estruturas da Membrana Celular , Ácido Cítrico , Pichia , Ácido Cítrico/farmacologia , Ácidos Graxos/farmacologia , Membrana Celular , Fluidez de MembranaRESUMO
Current small-molecule-based SARS-CoV-2 treatments have limited global accessibility and pose the risk of inducing viral resistance. Therefore, a marine algae and cyanobacteria extract library was screened for natural products that could inhibit two well-defined and validated COVID-19 drug targets, disruption of the spike protein/ACE-2 interaction and the main protease (Mpro) of SARS-CoV-2. Following initial screening of 86 extracts, we performed an untargeted metabolomic analysis of 16 cyanobacterial extracts. This approach led to the isolation of an unusual saturated fatty acid, jobosic acid (2,5-dimethyltetradecanoic acid, 1). We confirmed that 1 demonstrated selective inhibitory activity toward both viral targets while retaining some activity against the spike-RBD/ACE-2 interaction of the SARS-CoV-2 omicron variant. To initially explore its structure-activity relationship (SAR), the methyl and benzyl ester derivatives of 1 were semisynthetically accessed and demonstrated acute loss of bioactivity in both SARS-CoV-2 biochemical assays. Our efforts have provided copious amounts of a fatty acid natural product that warrants further investigation in terms of SAR, unambiguous determination of its absolute configuration, and understanding of its specific mechanisms of action and binding site toward new therapeutic avenues for SARS-CoV-2 drug development.
Assuntos
Antivirais , Metabolômica , SARS-CoV-2 , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Humanos , Cianobactérias/química , Relação Estrutura-Atividade , Ácidos Graxos/química , Ácidos Graxos/farmacologia , COVID-19 , Estrutura Molecular , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismoRESUMO
Phytochemical investigation of the fruit and flowers of Passiflora foetida led to the isolation of 14 compounds, of which five are previously undescribed fatty acid lactones. Four 2-pyrones, passifetilactones A-D (1-4), and one furanone, passifetilactone E (5), were identified by analysis of spectroscopic and spectrometric data. The previously undescribed lactones were tested for cytotoxic activities against the cancer cell lines HeLa, A549, PC-3, KKU-055, and KKU-213A and two normal cell lines, Vero and MMNK-1. Passifetilactones B (2) and C (3) displayed good to mild cytotoxic activity, at IC50 3.7-25.9 µM and 12.2-19.8 µM, respectively, against six cell lines, but were weakly active against the MMNK-1 cell line. Passifetilactones B and C (2 and 3) showed cell apoptosis induction on the KKU-055 cell line in a flow cytometry experiment. Passifetilactone D (4) is an isolation artifact produced by purification over silica gel, but we demonstrated that it can also be slowly formed within the crude EtOAc extract. This is the first investigation of the flowers and the fruit of this plant.
Assuntos
Antineoplásicos Fitogênicos , Flores , Frutas , Lactonas , Passiflora , Flores/química , Humanos , Frutas/química , Lactonas/química , Lactonas/farmacologia , Lactonas/isolamento & purificação , Passiflora/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Estrutura Molecular , Animais , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Ácidos Graxos/isolamento & purificação , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Células HeLa , Chlorocebus aethiops , Células VeroRESUMO
OBJECTIVES: Despite the growing rates of global obesity and the known positive associations between brown adipose tissue (BAT) and cardiovascular health, little is known about the metabolic effects of BAT activity in Samoans, a population at high risk of obesity and type II diabetes. Here we assessed the potential effects of inferred BAT activity on metabolic health markers in Samoan adults exposed to mild cold. METHODS: Using point-of-care finger prick technology we measured fasting glucose, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels before and after 30 min of cold exposure among 61 individuals (38 females, 23 males, ages 31-54) from 'Upolu Island, Samoa. Respiratory quotient was measured by indirect calorimetry to determine substrate metabolism at room temperature and cold exposure. RESULTS: Fasting glucose levels decreased significantly (p < .001) after cold exposure while neither total cholesterol (p = .88), HDL (p = .312), nor LDL (p = .089) changed. Respiratory quotient decreased significantly (p = .009) between exposures, suggesting an increased preference for lipid metabolism as a response to cold. CONCLUSIONS: The observed effects of inferred BAT activity on biomarkers suggest BAT activity utilizes both glucose and lipid-derived fatty acids as fuel for thermogenesis. Our work provides evidence for the beneficial metabolic effects of BAT and emphasizes the need for the population-specific development of metabolic treatments involving BAT to ensure the successful and equitable minimization of extreme consequences of obesity and metabolic health.
Assuntos
Diabetes Mellitus Tipo 2 , Glucose , População das Ilhas do Pacífico , Adulto , Feminino , Humanos , Masculino , Tecido Adiposo Marrom/fisiologia , Colesterol , Temperatura Baixa , Metabolismo Energético , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Glucose/metabolismo , Glucose/farmacologia , Obesidade , Termogênese , Pessoa de Meia-IdadeRESUMO
The association between dysbiotic microbiota biofilm and colon cancer has recently begun to attract attention. In the study, the apitherapeutic effects of bee products (honey, bee venom, royal jelly, pollen, perga and propolis) obtained from the endemic Yigilca ecotype of Apis mellifera anatoliaca were investigated. Antibiofilm activity were performed by microplate assay using crystal violet staining to measure adherent biofilm biomass of Escherichia coli capable of forming biofilms. Bee venom showed the highest inhibition effect (73.98%) at 50% concentration. Honey, perga and royal jelly reduced biofilm formation by >50% at all concentrations. The antiproliferation effect on the HCT116 colon cancer cell line was investigated with the watersoluble tetrazolium salt1 assay. After 48 h of honey application at 50% concentration, cell proliferation decreased by 86.51%. The high cytotoxic effects of royal jelly and bee venom are also remarkable. Additionally, apoptotic pathway analysis was performed by ELISA using caspase 3, 8 and 9 enzyme-linked immunosorbent assay kits. All bee products induced a higher expression of caspase 9 compared with caspase 8. Natural products that upregulate caspase proteins are promising therapeutic targets for proliferative diseases.
Assuntos
Antineoplásicos , Venenos de Abelha , Biofilmes , Neoplasias do Colo , Escherichia coli , Ácidos Graxos , Própole , Biofilmes/efeitos dos fármacos , Humanos , Animais , Venenos de Abelha/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Neoplasias do Colo/tratamento farmacológico , Abelhas/efeitos dos fármacos , Células HCT116 , Própole/farmacologia , Própole/química , Ácidos Graxos/farmacologia , Antineoplásicos/farmacologia , Mel , Proliferação de Células/efeitos dos fármacos , Pólen/química , Antibacterianos/farmacologia , Apoptose/efeitos dos fármacosRESUMO
Shrimp processing generates substantial waste, which is rich in valuable components such as polysaccharides, proteins, carotenoids, and fatty acids. This review provides a comprehensive overview of the valorization of shrimp waste, mainly shrimp shells, focusing on extraction methods, bioactivities, and potential applications of these bioactive compounds. Various extraction techniques, including chemical extraction, microbial fermentation, enzyme-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, and pressurized techniques are discussed, highlighting their efficacy in isolating polysaccharides, proteins, carotenoids, and fatty acids from shrimp waste. Additionally, the bioactivities associated with these compounds, such as antioxidant, antimicrobial, anti-inflammatory, and antitumor properties, among others, are elucidated, underscoring their potential in pharmaceutical, nutraceutical, and cosmeceutical applications. Furthermore, the review explores current and potential utilization avenues for these bioactive compounds, emphasizing the importance of sustainable resource management and circular economy principles in maximizing the value of shrimp waste. Overall, this review paper aims to provide insights into the multifaceted aspects of shrimp waste valorization, offering valuable information for researchers, industries, and policymakers interested in sustainable resource utilization and waste-management strategies.
Assuntos
Penaeidae , Gerenciamento de Resíduos , Animais , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/química , Carotenoides/farmacologia , Carotenoides/isolamento & purificação , Carotenoides/química , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Penaeidae/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/química , Proteínas/isolamento & purificação , Gerenciamento de Resíduos/métodos , ResíduosRESUMO
Objective: This study aimed to evaluate the expression of genes involved in cholesterol metabolism and establish their association with oxidative stress (OS). Methods: We employed an in vitro experimental design and cells were divided into six groups: C (control), CH (HepG2 + H2O2), CHN (HepG2 + H2O2 + NAC), F (FFA-treated HepG2), FH (FFA-treated HepG2 + H2O2), and FHN (FFA-treated HepG2 + H2O2 + NAC). Cell viability was assessed using the MTT assay, while successful FFA model establishment was confirmed via Oil Red staining and absorbance. Oxidative stress injury was gauged by measuring ROS, SOD activity, and MDA content. RNA transcription and protein expression of cholesterol-related (DHCR24, DHCR7) and oxidative stress-related (NFE2L2, HMOX1) genes were also examined via RT-qPCR and WB. Results: The impact of H2O2 on cell viability exhibited a time-dose-dependent pattern, paralleling the changes in reactive oxygen species (ROS) levels. Compared to the C group, FFA treatment led to an increase in Oil Red absorption and MDA content and decreased SOD activity. However, it did not result in a significant reduction in cell viability. The FH group exhibited reduced cell viability and SOD activity, along with a further elevation in MDA content compared to the F group. Furthermore, the increased SOD activity and decreased MDA content observed in the CH group were effectively reversed following NAC treatment. Such a reversal was not evident between the FHN and FH groups. Compared to the control group, genes associated with cholesterol metabolism and oxidative stress (OS) displayed heightened expression levels in the other treatment groups, with the FHN group showing lower expression levels than the FH group. Notably, changes in the protein expressions of DHCR24, DHCR7, NFE2L2, and HMOX1 were consistent and exhibited correlations. Conclusions: Cholesterol metabolism emerges as a potential mechanism underlying H2O2-induced oxidative stress injury in HepG2 cells treated with FFA.
Assuntos
Ácidos Graxos , Peróxido de Hidrogênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Peróxido de Hidrogênio/farmacologia , Ácidos Graxos/farmacologia , Células Hep G2 , Estresse Oxidativo , Colesterol/farmacologia , Superóxido Dismutase , ApoptoseRESUMO
Renal interstitial fibrosis (RIF) is the main pathological basis for the progression of chronic kidney disease (CKD), however, effective interventions are limited. Here, we investigated the effect of Icariside II (ICA-II) on RIF and explored the underlying mechanisms. Rats receiving 5/6 ablation and infarction (A/I) surgery were gavaged with ICA-II (5 or 10 mg/kg) for 8 weeks. In vitro, TGF-ß1-stimulated NRK-52E cells were treated with ICA-II and (or) oleic acid, etomoxir, ranolazine, fenofibrate, and GW6471. The effects of ICA-II on RIF, fatty acid oxidation, lipid deposition, and mitochondrial function were determined by immunoblotting, Oil red O staining, colorimetric, and fluorometric assays. Using adeno-associated virus injection and co-culture methods, we further determined mechanisms of ICA-II anti-RIF. ICA-II ameliorated the fibrotic responses in vivo and in vitro. RNA-seq analysis indicated that ICA-II regulated fatty acid degradation and PPAR pathway in 5/6 (A/I) kidneys. ICA-II attenuated lipid accumulation and up-regulated expression of PPARα, CPT-1α, Acaa2, and Acadsb proteins in vivo and in vitro. Compared to ICA-II treatment, ICA-II combined with Etomoxir exacerbated mitochondrial dysfunction and fibrotic responses in TGF-ß-treated NRK-52E cells. Importantly, we determined that ICA-II improved lipid metabolism, fatty acid oxidation, mitochondrial function, and RIF by restoring PPARα. Co-culture revealed that ICA-II decreased the expression of Fibronectin, Collagen-I, α-SMA, and PCNA proteins in NRK-49F cells by restoring PPARα of renal tubular cells. ICA-II may serve as a promising therapeutic agent for RIF in 5/6 (A/I) rats, which may be important for the prevention and treatment of CKD.
Assuntos
Compostos de Epóxi , Flavonoides , Nefropatias , Insuficiência Renal Crônica , Ratos , Animais , PPAR alfa/metabolismo , Linhagem Celular , Nefropatias/tratamento farmacológico , Rim , Fator de Crescimento Transformador beta1/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Ácidos Graxos/farmacologia , Metabolismo dos Lipídeos , Fibrose , LipídeosRESUMO
The fatty acid profile, antioxidant/antibacterial, and cytotoxic effects of the extracts obtained from Jurinea turcica B.Dogan& A.Duran have been evaluated for the first time in the current study. The fatty acid profile of ethanolic extracts was determined using the Soxhlet extractor by a gas chromatography-mass spectrometer. The antioxidant and antibacterial activities were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferrous reduction tests and the disc diffusion technique. Additionally, the cytotoxicity and wound healing assays were performed on A549 cells. The highest amount of component in the leaf extract was docosanoic acid methyl ester, whereas abundant arachidonic acid methyl ester was mainly found in the flower extract. The IC50 values, the 50 % scavenging value for the DPPH radical, were 179.13 and 124.67â µg/mL for the leaf and flower extracts, respectively. IC50 values (the half-maximal inhibitory concentration) were 10.4 and 24.7â µg/mL for the flower and leaf extracts, respectively. The leaf extract showed more potent antibacterial activity on Enterococcus faecalis (17â mm) and Staphylococcus aureus (16â mm) bacteria than the flower extract. In conclusion, the extracts of J. turcica have anti-cancerogenic and antibacterial effects. Leaf extracts have antibacterial and anti-metastatic effects, while flower extracts show antioxidant, cytotoxic, and apoptotic properties in A549 cells.
Assuntos
Antineoplásicos , Antioxidantes , Antioxidantes/farmacologia , Antioxidantes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Ácidos Graxos/farmacologia , ÉsteresRESUMO
Royal jelly (RJ) is a highly nutritious natural product with great potential for use in medicine, cosmetics, and as a health-promoting food. This bee product is a mixture of important compounds, such as proteins, vitamins, lipids, minerals, hormones, neurotransmitters, flavonoids, and polyphenols, that underlie the remarkable biological and therapeutic activities of RJ. Various bioactive molecules like 10-hydroxy-2-decenoic acid (10-HDA), antibacterial protein, apisin, the major royal jelly proteins, and specific peptides such as apisimin, royalisin, royalactin, apidaecin, defensin-1, and jelleins are characteristic ingredients of RJ. RJ shows numerous physiological and pharmacological properties, including vasodilatory, hypotensive, antihypercholesterolaemic, antidiabetic, immunomodulatory, anti-inflammatory, antioxidant, anti-aging, neuroprotective, antimicrobial, estrogenic, anti-allergic, anti-osteoporotic, and anti-tumor effects. Moreover, RJ may reduce menopause symptoms and improve the health of the reproductive system, liver, and kidneys, and promote wound healing. This article provides an overview of the molecular mechanisms underlying the beneficial effects of RJ in various diseases, aging, and aging-related complications, with special emphasis on the bioactive components of RJ and their health-promoting properties. The data presented should be an incentive for future clinical studies that hopefully will advance our knowledge about the therapeutic potential of RJ and facilitate the development of novel RJ-based therapeutic opportunities for improving human health and well-being.