RESUMO
Recently, the increasing incidence of malignant melanoma has become a major public health concern owing to its poor prognosis and impact on quality of life. Consuming foods with potent antitumor compounds can help prevent melanoma and maintain skin health. Fucoxanthin (FX), a naturally occurring carotenoid found in brown algae, possesses antitumor properties. However, its bioavailability, safety risks, and in vivo effects and mechanisms against melanoma remain unclear. This research focused on evaluating the safety and prospective antimelanoma impact of simulated gastrointestinal digestion products (FX-ID) on HaCaT and A375 cells.The results indicate that FX-ID exerts negative effects on mitochondria in A375 cells, increases Bax expression, releases Cytochrome C, and activates cleaved caspase-3, ultimately promoting apoptosis. Additionally, FX-ID influences the mitogen-activated protein kinase (MAPK) pathway by enhancing cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) levels, consequently facilitating apoptosis and inflammation without significantly impacting HaCaT cells. These findings provide insight into inhibitory mechanism of FX-ID against melanoma, guiding the development of functional foods for prevention.
Assuntos
Apoptose , Queratinócitos , Melanoma , Xantofilas , Humanos , Melanoma/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Apoptose/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/química , Linhagem Celular Tumoral , NF-kappa B/metabolismo , NF-kappa B/genética , Digestão , Modelos Biológicos , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Antineoplásicos/farmacologia , Antineoplásicos/química , Phaeophyceae/química , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 3/genéticaRESUMO
Hydrophobic bioactive compounds like astaxanthin (AST) exhibit poor water solubility and low bioavailability. Liposomes, which serve as nanocarriers, are known for their excellent biocompatibility and minimal immunogenicity. Traditionally, liposomes have been primarily constructed using phospholipids and cholesterol. However, the intake of cholesterol may pose a risk to human health. Phytosterol ester was reported to reduce level of cholesterol and improve properties of liposomes. In this study, phytosterol oleate was used to prepare liposomes instead of cholesterol to deliver AST (AST-P-Lip). The size range of AST-P-Lip was 100-220 nm, and the morphology was complete and uniform. In vitro studies showed that AST-P-Lip significantly enhanced the antioxidant activity and oral bioavailability of AST. During simulated digestion, AST-P-Lip protected AST from damage by gastric and intestinal digestive fluid. Additionally, AST-P-Lip had a good storage stability and safety. These results provide references for the preparation of novel liposomes and the delivery of bioactive compounds.
Assuntos
Colesterol , Lipossomos , Fitosteróis , Xantofilas , Lipossomos/química , Xantofilas/química , Xantofilas/farmacologia , Xantofilas/administração & dosagem , Humanos , Fitosteróis/química , Fitosteróis/farmacologia , Fitosteróis/administração & dosagem , Colesterol/química , Tamanho da Partícula , Disponibilidade Biológica , Ácido Oleico/química , Composição de Medicamentos , Animais , Antioxidantes/química , Antioxidantes/farmacologiaRESUMO
Fucoxanthin (Fx) has garnered significant interest due to its exceptional biological properties. However, its efficacy in enhancing food quality and human health is contingent upon the solubility of the compound in water and its physicochemical stability. Therefore, nanocarriers must be developed to enhance the stability and biocompatibility of Fx. In this study, oxidized paramylon and Fx self-assembled nanoparticles (Fx-OEP) were prepared via the anti-solvent method, with a loading rate of 82.47 % for Fx. The Fx-OEP exhibited robust storage and photostability. In vitro simulated digestion assays demonstrated that Fx-OEP effectively protected Fx from premature gastric release, while achieving a release efficiency of 72.17 % in the intestinal phase. Fx-OEP has the capacity to scavenge a range of reactive oxygen species (ROS) induced by cellular oxidative stress. Treatment with Fx-OEP resulted in a significant reduction in ROS accumulation in insulin-resistant HepG2 cells, which was attributed to the activation of the nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. This, in turn, activated insulin receptor substrate 1/glucose transporter type 4 (IRS1/GLUT4), promoting cellular glucose absorption and utilization. These findings indicate the potential of self-assembled nanoparticles based on oxidized paramylon as a new type of nanocarrier for delivering hydrophobic substances.
Assuntos
Resistência à Insulina , Nanopartículas , Xantofilas , Humanos , Xantofilas/farmacologia , Xantofilas/química , Nanopartículas/química , Células Hep G2 , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Portadores de Fármacos/química , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Liberação Controlada de Fármacos , Glucanos/química , Glucanos/farmacologiaRESUMO
Fucoxanthin (Fx), a xanthophyll carotenoid abundant in brown algae, possesses several biological functions, such as antioxidant, anti-inflammatory, and cardiac-protective activities. However, the role of Fx in myocardial ischemia/reperfusion (MI/R) is still unclear. Thus, the aim of this study was to investigate the effect of Fx on MI/R-induced injury and explore the underlying mechanisms. Our results showed that in vitro, Fx treatment significantly suppressed inflammatory response, oxidative stress, and apoptosis in rat cardiomyocytes exposed to hypoxia/reoxygenation (H/R). In addition, Fx led to increased phosphorylation of AMPK, AKT, and GSK-3ß, and enhanced activation of Nrf2 in cardiomyocytes under H/R conditions. Notably, pretreatment with Compound C (AMPK inhibitor), partially reduced the beneficial effects of Fx in cardiomyocytes exposed to H/R. In vivo, Fx ameliorated myocardial damage, inhibited inflammatory response, oxidative stress, and apoptosis, and activated the AMPK/GSK-3ß/Nrf2 signaling in myocardial tissues in MI/R rat model. Taken together, these findings indicated that Fx attenuates MI/R-induced injury by inhibiting oxidative stress, inflammatory response, and apoptosis. The AMPK/GSK-3ß/Nrf2 pathway is involved in the cardioprotective effect of Fx in MI/R injury. Thus, Fx may be a promising drug for the treatment of MI/R.
Assuntos
Proteínas Quinases Ativadas por AMP , Apoptose , Glicogênio Sintase Quinase 3 beta , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Transdução de Sinais , Xantofilas , Animais , Ratos , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/químicaRESUMO
Phaeodactylum tricornutum (PT) is a microalgae extract that contains fucoxanthin and has been shown to enhance cognitive function in younger populations. The present study assessed if PT supplementation affects cognition in healthy, young-old, physically active adults with self-perceptions of cognitive and memory decline. METHODS: Forty-three males and females (64.3 ± 6.0 years, 79.8 ± 16.0 kg, 27.0 ± 4.0 kg/m2) with perceptions of cognitive and memory decline completed the double-blind, randomized, parallel-arm, placebo-controlled intervention clinical trial. Participants were counterbalanced by sex and BMI and randomly allocated to their respective 12-week supplementation interventions, which were either the placebo (PL) or 1100 mg/day of PT containing 8.8 mg of fucoxanthin (FX). Fasting blood samples were collected, and cognitive assessments were performed during the testing session at 0, 4, and 12 weeks of intervention. The data were analyzed by multivariate and univariate general linear model (GLM) analyses with repeated measures, pairwise comparisons, and mean changes from baseline analysis with 95% confidence intervals (CIs) to assess the clinical significance of the findings. RESULTS: FX supplementation significantly affected (p < 0.05) or exhibited tendencies toward significance (p > 0.05 to p < 0.10 with effect sizes ranging from medium to large) for word recall, picture recognition reaction time, Stroop color-word test, choice reaction time, and digit vigilance test variables. Additionally, FX supplementation promoted a more consistent clinical improvement from baseline values when examining mean changes with 95% CIs, although most differences were seen over time rather than between groups. CONCLUSIONS: The results demonstrate some evidence that FX supplementation can improve working and secondary memory, vigilance, attention, accuracy, and executive function. There was also evidence that FX promoted more positive effects on insulin sensitivity and perceptions about sleep quality with no negative effects on clinical blood panels or perceived side effects. Additional research should investigate how FX may affect cognition in individuals perceiving memory and cognitive decline. Registered clinical trial #NCT05759910.
Assuntos
Cognição , Disfunção Cognitiva , Suplementos Nutricionais , Microalgas , Xantofilas , Humanos , Masculino , Feminino , Cognição/efeitos dos fármacos , Pessoa de Meia-Idade , Método Duplo-Cego , Xantofilas/farmacologia , Xantofilas/administração & dosagem , Idoso , Biomarcadores/sangue , DiatomáceasRESUMO
Microcystin-LR (MC-LR), frequently generated by cyanobacteria, has been demonstrated to raise the likelihood of liver disease. Few previous studies have explored the potential antagonist against MC-LR. Astaxanthin (ASX) has been shown to possess various beneficial effects in regulating lipid metabolism in the liver. However, whether ASX could alleviate MC-LR-induced hepatic lipid metabolic dysregulation is as yet unclear. In this work, the important roles and mechanisms of ASX in countering MC-LR-induced liver damage and lipid metabolic dysregulation were explored for the first time. The findings revealed that ASX not only prevented weight loss but also enhanced liver health after MC-LR exposure. Moreover, ASX effectively decreased triglyceride, total cholesterol, aspartate transaminase, and alanine aminotransferase contents in mice that were elevated by MC-LR. Histological observation showed that ASX significantly alleviated lipid accumulation and inflammation induced by MC-LR. Mechanically, ASX could significantly diminish the expression of genes responsible for lipid generation (Srebp-1c, Fasn, Cd36, Scd1, Dgat1, and Pparg), which probably reduced lipid accumulation induced by MC-LR. Analogously, MC-LR increased intracellular lipid deposition in THLE-3 cells, while ASX decreased these symptoms by down-regulating the expression of key genes in the lipid synthesis pathway. Our results implied that ASX played a crucial part in lipid synthesis and effectively alleviated MC-LR-induced lipid metabolism dysregulation. ASX might be developed as a novel protectant against hepatic impairment and lipid metabolic dysregulation associated with MC-LR. This study offers new insights for further management of MC-LR-related metabolic diseases.
Assuntos
Metabolismo dos Lipídeos , Fígado , Toxinas Marinhas , Microcistinas , Xantofilas , Microcistinas/toxicidade , Animais , Xantofilas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controleRESUMO
Fucoxanthin, a dietary carotenoid, is predominantly found in edible brown algae and is commonly consumed worldwide. Fucoxanthin has been shown to possess beneficial health activities such as antidiabetic, anti-inflammatory, antimutagenic, and antiobesity; however, the effects of fucoxanthin on VEGF-mediated angiogenesis and its possible binding with VEGF are unknown. Here, different lines of evidence supported the suppressive roles of fucoxanthin in VEGF-mediated angiogenesis. In human umbilical vein endothelial cells, fucoxanthin remarkedly suppressed VEGF-mediated cell proliferative, migration, and invasive abilities, as well as tube formation, without cytotoxicity. In addition, fucoxanthin inhibited the subintestinal vessel formation of zebrafish in vivo. In signaling cascades, fucoxanthin was proposed to interact with VEGF, thus attenuating VEGF's functions in activating the VEGF receptor and its related downstream signaling, i.e., phosphorylations of MEK and Erk. Fucoxanthin also significantly blocked VEGF-triggered ROS formation. Furthermore, the outcomes of applying fucoxanthin in cancer cells were identified, which included (i) inhibiting VEGF-mediated cell proliferation and migration and (ii) inhibiting NF-κB translocation via limiting MMP2 expression. These lines of investigations supported the antiangiogenic roles of fucoxanthin, as well as reviewing its signaling mechanisms, in blocking the VEGF-triggered responses. The results would benefit the potential development of fucoxanthin for the prevention and treatment of angiogenesis-related diseases.
Assuntos
Movimento Celular , Proliferação de Células , Células Endoteliais da Veia Umbilical Humana , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Xantofilas , Peixe-Zebra , Humanos , Xantofilas/farmacologia , Xantofilas/química , Transdução de Sinais/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/química , Phaeophyceae/química , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , AngiogêneseRESUMO
BACKGROUND: Staphylococcus aureus is an infectious bacterium that is frequently found in healthcare settings and the community. This study aimed to prepare rutin-loaded chitosan nanoparticles (Rut-CS NPs) and assess their antibacterial activity against pathogenic strains of S. aureus. RESULTS: The synthesized Rut-CS NPs exhibited an amorphous morphology with a size ranging from 160 to 240 nm and a zeta potential of 37.3 mV. Rut-CS NPs demonstrated significant antibacterial activity against S. aureus strains. Following exposure to Rut-CS NPs, the production of staphyloxanthin pigment decreased by 43.31-89.63%, leading to increased susceptibility of S. aureus to hydrogen peroxide. Additionally, visual inspection of cell morphology indicated changes in membrane integrity and permeability upon Rut-CS NPs exposure, leading to a substantial increase (107.07-191.08%) in cytoplasmic DNA leakage in the strains. Furthermore, ½ MIC of Rut-CS NPs effectively inhibited the biofilm formation (22.5-37.5%) and hemolytic activity (69-82.59%) in the S. aureus strains. CONCLUSIONS: Our study showcases that Rut-CS NPs can serve as a novel treatment agent to combat S. aureus infections by altering cell morphology and inhibiting virulence factors of S. aureus.
Assuntos
Antibacterianos , Biofilmes , Quitosana , Testes de Sensibilidade Microbiana , Nanopartículas , Rutina , Staphylococcus aureus , Xantofilas , Staphylococcus aureus/efeitos dos fármacos , Quitosana/farmacologia , Quitosana/química , Rutina/farmacologia , Rutina/química , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/química , Hemólise/efeitos dos fármacos , Fatores de Virulência , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Humanos , Peróxido de Hidrogênio/farmacologiaRESUMO
Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.
Assuntos
Movimento Celular , Proliferação de Células , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Xantofilas , Humanos , Serina-Treonina Quinases TOR/metabolismo , Xantofilas/farmacologia , Xantofilas/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Metástase Neoplásica , Simulação de Acoplamento MolecularRESUMO
Fucoxanthin, a carotenoid with remarkable antioxidant properties, has considerable potential for high-value biotechnological applications in the pharmaceutical, nutraceutical, and cosmeceutical fields. However, conventional extraction methods of this molecule from microalgae are limited in terms of cost-effectiveness. This study focused on optimizing biomass and fucoxanthin production from Isochrysis galbana, isolated from the coast of Tadjoura (Djibouti), by testing various culture media. The antioxidant potential of the cultures was evaluated based on the concentrations of fucoxanthin, carotenoids, and total phenols. Different nutrient formulations were tested to determine the optimal combination for a maximum biomass yield. Using the statistical methodology of principal component analysis, Walne and Guillard F/2 media were identified as the most promising, reaching a maximum fucoxanthin yield of 7.8 mg/g. Multiple regression models showed a strong correlation between antioxidant activity and the concentration of fucoxanthin produced. A thorough study of the optimization of I. galbana growth conditions, using a design of experiments, revealed that air flow rate and CO2 flow rate were the most influential factors on fucoxanthin production, reaching a value of 13.4 mg/g. Finally, to validate the antioxidant potential of fucoxanthin, an in silico analysis based on molecular docking was performed, showing that fucoxanthin interacts with antioxidant proteins (3FS1, 3L2C, and 8BBK). This research not only confirmed the positive results of I. galbana cultivation in terms of antioxidant activity, but also provided essential information for the optimization of fucoxanthin production, opening up promising prospects for industrial applications and future research.
Assuntos
Antioxidantes , Biologia Computacional , Haptófitas , Microalgas , Xantofilas , Microalgas/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Xantofilas/isolamento & purificação , Xantofilas/farmacologia , Xantofilas/química , Haptófitas/química , Biomassa , Meios de Cultura/química , Simulação de Acoplamento Molecular , Fenóis/farmacologia , Fenóis/químicaRESUMO
Tendinopathy is one of the most frequent musculoskeletal disorders characterized by sustained tissue inflammation and oxidative stress, accompanied by extracellular matrix remodeling. Patients suffering from this pathology frequently experience pain, swelling, stiffness, and muscle weakness. Current pharmacological interventions are based on nonsteroidal anti-inflammatory drugs; however, the effectiveness of these strategies remains ambiguous. Accumulating evidence supports that oral supplementation of natural compounds can provide preventive, and possibly curative, effects. Vitamin C (Vit C), collagen peptides (Coll), resveratrol (Res), and astaxanthin (Asx) were reported to be endowed with potential beneficial effects based on their anti-inflammatory and antioxidant activities. Here, we analyzed the efficacy of a novel combination of these compounds (Mix) in counteracting proinflammatory (IL-1ß) and prooxidant (H2O2) stimuli in human tenocytes. We demonstrated that Mix significantly impairs IL-6-induced IL-1ß secretion, NF-κB nuclear translocation, and MMP-2 production; notably, a synergistic effect of Mix over the single compounds could be observed. Moreover, Mix was able to significantly counteract H2O2-triggered ROS production. Together, these results point out that Mix, a novel combination of Vit C, Coll, Resv, and Asx, significantly impairs proinflammatory and prooxidant stimuli in tenocytes, mechanisms that contribute to the onset of tendinopathies.
Assuntos
Anti-Inflamatórios , Antioxidantes , Ácido Ascórbico , Colágeno , Resveratrol , Tendinopatia , Tenócitos , Xantofilas , Humanos , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Resveratrol/farmacologia , Antioxidantes/farmacologia , Xantofilas/farmacologia , Xantofilas/uso terapêutico , Tendinopatia/tratamento farmacológico , Tendinopatia/metabolismo , Colágeno/metabolismo , Anti-Inflamatórios/farmacologia , Tenócitos/metabolismo , Tenócitos/efeitos dos fármacos , Interleucina-1beta/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Peróxido de Hidrogênio/metabolismo , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Células Cultivadas , Estresse Oxidativo/efeitos dos fármacosRESUMO
This study aimed to elaborate the combination effect of polysaccharides on physicochemical properties and in vitro digestive behavior of astaxanthin (AST)-loaded Pickering emulsion gel. AST-loaded Pickering emulsion gel was prepared by heating Pickering emulsion with konjac glucomannan (KGM) and κ-carrageenan (CRG). The microstructure revealed that adding the two polysaccharides resulted in Pickering emulsion forming a network structure. It exhibited a denser and more uniform network structure, enhancing its mechanical properties four times and increasing its water-holding capacity by 20 %. In vitro digestion experiments demonstrated that the release of free fatty acids from the Pickering emulsion gel (4.25 %) was notably lower than that from conventional Pickering emulsion (17.19 %), whereas AST bioaccessibility was remarkably low at 0.003 %. It provided a feasible strategy to regulate the bioaccessibility in Pickering emulsion, which has theoretical significance to guide the current eutrophic diet people.
Assuntos
Carragenina , Emulsões , Géis , Mananas , Xantofilas , Mananas/química , Carragenina/química , Emulsões/química , Xantofilas/química , Xantofilas/farmacologia , Géis/química , Digestão/efeitos dos fármacos , Fenômenos QuímicosRESUMO
Fucoxanthin (FX), a non-provitamin-A carotenoid, is a well-known major xanthophyll contained in edible brown algae. The nanoencapsulation of FX was motivated due to its multiple activities. Here, nano-encapsulated-FX (nano-FX) was prepared according to our early method by using whey protein and flaxseed gum as the biomacromolecule carrier material, then in vivo antitumor effect and mechanism of nano-FX on xenograft mice were investigated. Thirty 4-week-old male BALB/c nude mice were fed adaptively for 7 days to establish xenograft tumor model with Huh-7 cells. The tumor-bearing mice consumed nano-FX (50, 25, and 12.5 mg kg-1) and doxorubicin hydrochloride (DOX, 1 mg kg-1) or did not consume (Control) for 21 days, n = 6. The tumor inhibition rates of nano-FX were as high as 54.67 ± 1.04 %. Nano-FX intervention promoted apoptosis and induced hyperchromatic pyknosis and focal necrosis in tumor tissue by down-regulating the expression of p-JNK, p-ERK, PI3Kp85α, p-AKT, p-p38MAPK, Bcl-2, CyclinD1 and Ki-67, while up-regulating the expression of cleaved caspase-3 and Bax. Nano-FX inhibited tumor growth and protected liver function of tumor bearing mice in a dose-dependent manner, up-regulate the level of apoptosis-related proteins, inhibit the MAPK-PI3K/Akt pathways, and promote tumor cell apoptosis.
Assuntos
Apoptose , Camundongos Nus , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas do Soro do Leite , Xantofilas , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Linhagem Celular Tumoral , Xantofilas/farmacologia , Xantofilas/química , Proteínas do Soro do Leite/química , Proteínas do Soro do Leite/farmacologia , Masculino , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
This in vivo study performed in rat adjuvant arthritis aims to advance the understanding of astaxanthin's therapeutic properties for the possible treatment of rheumatoid arthritis (RA) in monotherapy and along with the standard RA treatment, methotrexate (MTX), in combination therapy. The main goal was to elucidate astaxanthin's full therapeutic potential, evaluate its dose dependency, and compare its effects in monotherapy with other carotenoids such as ß-carotene and ß-cryptoxanthin (KXAN). Moreover, potential differences in therapeutic activity caused by using different sources of astaxanthin, synthetic (ASYN) versus isolated from Blakeslea trispora (ASTAP), were evaluated using one-way ANOVA (Tukey-Kramer post hoc test). KXAN was the most effective in reducing plasma MMP-9 levels in monotherapy, significantly better than MTX, and in reducing hind paw swelling. The differences in the action of ASTAP and ASYN have been observed across various biometric, anti-inflammatory, and antioxidative parameters. In combined therapy with MTX, the ASYN + MTX combination proved to be better. These findings, especially the significant anti-arthritic effect of KXAN and ASYN + MTX, could be the basis for further preclinical studies.
Assuntos
Artrite Experimental , Metotrexato , Xantofilas , Animais , Xantofilas/farmacologia , Xantofilas/uso terapêutico , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Ratos , Masculino , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Quimioterapia Combinada , Sinergismo Farmacológico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , beta-Criptoxantina/farmacologia , beta Caroteno/farmacologia , Antioxidantes/farmacologiaRESUMO
Antibacterial resistance causes around 1.27 million deaths annually around the globe and has been recognized as a top 3 priority health threat. Antimicrobial photodynamic therapy (aPDT) is considered a promising alternative to conventional antibiotic treatments. Algal lipid extracts have shown antibacterial effects when used as photosensitizers (PSs) in aPDT. In this work we assessed the photodynamic efficiency of lipidic extracts of microalgae belonging to different phyla (Bacillariophyta, Chlorophyta, Cyanobacteria, Haptophyta, Ochrophyta and Rhodophyta). All the extracts (at 1 mg mL-1) demonstrated a reduction of Staphylococcus aureus >3 log10 (CFU mL-1), exhibiting bactericidal activity. Bacillariophyta and Haptophyta extracts were the top-performing phyla against S. aureus, achieving a reduction >6 log10 (CFU mL-1) with light doses of 60 J cm-2 (Bacillariophyta) and 90 J cm-2 (Haptophyta). The photodynamic properties of the Bacillariophyta Phaeodactylum tricornutum and the Haptophyta Tisochrysis lutea, the best effective microalgae lipid extracts, were also assessed at lower concentrations (75 µg mL-1, 7.5 µg mL-1, and 3.75 µg mL-1), reaching, in general, inactivation rates higher than those obtained with the widely used PSs, such as Methylene Blue and Chlorine e6, at lower concentration and light dose. The presence of chlorophyll c, which can absorb a greater amount of energy than chlorophylls a and b; rich content of polyunsaturated fatty acids (PUFAs) and fucoxanthin, which can also produce ROS, e.g. singlet oxygen (1O2), when photo-energized; a lack of photoprotective carotenoids such as ß-carotene, and low content of tocopherol, were associated with the algal extracts with higher antimicrobial activity against S. aureus. The bactericidal activity exhibited by the extracts seems to result from the photooxidation of microalgae PUFAs by the 1O2 and/or other ROS produced by irradiated chlorophylls/carotenoids, which eventually led to bacterial lipid peroxidation and cell death, but further studies are needed to confirm this hypothesis. These results revealed the potential of an unexplored source of natural photosensitizers (microalgae lipid extracts) that can be used as PSs in aPDT as an alternative to conventional antibiotic treatments, and even to conventional PSs, to combat antibacterial resistance.
Assuntos
Lipídeos , Microalgas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Microalgas/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Lipídeos/química , Xantofilas/farmacologia , Xantofilas/química , Luz , Clorofila/química , Clorofila/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Diatomáceas/química , Haptófitas/química , Oxigênio Singlete/metabolismo , Testes de Sensibilidade Microbiana , Rodófitas/químicaRESUMO
The common presence of glycidyl esters (GEs) in refined vegetable oils has been a concern for food safety. The present study aimed to investigate the inhibitory effects of three carotenoids derived from Haematococcus pluvialis microalga on GE formation in both rice oil and a chemical model during heating. The addition of astaxanthin (AS), lutein (LU), and ß-carotene (CA) at 0.6 mg/g in rice oil can reduce GE formation by 65.0%, 57.1%, and 57.5%, respectively, which are significantly higher than those achieved by common antioxidants such as l-ascorbyl palmitate (39.0%), α-tocopherol (18.5%), tert-butyl hydroquinone (42.7%), and quercetin (26.2%). UPLC-Q-TOF-MS/MS analysis showed that two new compounds, that is, propylene glycol monoester and diester of palmitic acid, were formed in the CA-added chemical model, which provided direct experimental evidence for the inhibition of antioxidants including AS, LU, and CA against GE formation not only by indirect antioxidative action but also by direct radical reactions to competitively prevent the formation of cyclic acyloxonium intermediates. Furthermore, it was interestingly found that only AS could react with the GEs. The adduct of AS with GEs, astaxanthin-3-O-propanetriol esters, was preliminarily identified using Q-TOF-MS/MS in the heated AS-GE model, suggesting that reacting with GEs might represent another distinct mechanism of AS to eliminate GEs.
Assuntos
Carotenoides , Ésteres , Temperatura Alta , Ésteres/química , Ésteres/farmacologia , Carotenoides/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Xantofilas/química , Xantofilas/farmacologia , Espectrometria de Massas em Tandem , Compostos de Epóxi/química , Modelos Químicos , Antioxidantes/química , Antioxidantes/farmacologia , Luteína/química , Luteína/farmacologia , Clorofíceas/química , Clorófitas/químicaRESUMO
The present study evaluated the cardioprotective effect of astaxanthin (ASX) against isoproterenol (ISO) induced myocardial infarction in rats via the pathway of mitochondrial biogenesis as the possible molecular target of astaxanthin. The control group was injected with normal physiological saline subcutaneously for 2 days. The second group was injected with ISO at a dose of 85 mg/kg bwt subcutaneously for 2 days. The third, fourth and fifth groups were supplemented with ASX at doses of 10, 20, 30 mg/kg bwt, respectively daily by oral gavage for 21 days then injected with ISO dose of 85 mg/kg bwt subcutaneously for 2 successive days. Isoproterenol administration in rats elevated the activities of Creatine kinase-MB (CK-MB), aspartate transaminase (AST), lactate dehydrogenase (LDH), and other serum cardiac biomarkers Troponin-I activities, oxidative stress biomarkers, malondialdehyde(MDA), Nuclear factor-kappa B (NF-KB), while it decreased Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), Nuclear factor erythroid-2-related factor 2 (Nfe212), mitochondrial transcriptional factor A (mt TFA), mitochondrial DNA copy number and glutathione system parameters. However, Astaxanthin decreased the activities of serum AST, LDH, CK-MB, and Troponin I that elevated by ISO. In addition, it increased glutathione peroxidase and reductase activities, total glutathione and reduced GSH content, and GSH/GSSG ratio, mtDNA copy number, PGC-1α expression and Tfam expression that improved mitochondrial biogenesis while it decreased GSSG and MDA contents and NF-KB level in the cardiac tissues. This study indicated that astaxanthin relieved isoproterenol induced myocardial infarction via scavenging free radicals and reducing oxidative damage and apoptosis in cardiac tissue.
Assuntos
Antioxidantes , Isoproterenol , Infarto do Miocárdio , Xantofilas , Animais , Xantofilas/farmacologia , Isoproterenol/toxicidade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Ratos , Masculino , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacosRESUMO
In this study, we evaluated the hepatoprotective effects of astaxanthin, a natural carotenoid, against the cholestatic liver fibrosis induced by bile duct ligation (BDL). Toward this end, male rats were subjected to BDL and treated with astaxanthin for 35 days. Afterwards, their serum and liver biochemical factors were assessed. Also, histopathological and immunohistochemical analyses were performed to determine the fibrosis and the expression levels of alpha-smooth muscle actin (α-SMA) and transforming growth factor beta (TGF-ß1) in the liver tissue. Based on the results, BDL caused a significant increase in liver enzyme levels, blood lipids, and bilirubin, while decreasing the activity of superoxide dismutase(SOD), catalase (CAT), and glutathione (GSH) enzymes. Also, in the BDL rats, hepatocyte necrosis, infiltration of inflammatory lymphocytes, and hyperplasia of bile ducts were detected, along with a significant increase in α-SMA and TGF-ß1 expression. Astaxanthin, however, significantly prevented the BDL's detrimental effects. In all, 10 mg/kg of this drug maintained the bilirubin and cholesterol serum levels of BDL rats at normal levels. It also reduced the liver enzymes' activity and serum lipids, while increasing the SOD, CAT, and GSH activity in BDL rats. The expression of α-SMA and TGF-ß1 in the BDL rats treated with 10 mg/kg of astaxanthin was moderate (in 34%-66% of cells) and no considerable cholestatic fibrosis was observed in this group. However, administrating the 20 mg/kg of astaxanthin was not effective in this regard. These findings showed that astaxanthin could considerably protect the liver from cholestatic damage by improving the biochemical features and regulating the expression of related proteins.
Assuntos
Ductos Biliares , Colestase , Cirrose Hepática , Ratos Wistar , Xantofilas , Animais , Xantofilas/farmacologia , Xantofilas/uso terapêutico , Masculino , Ratos , Colestase/patologia , Colestase/metabolismo , Colestase/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Ligadura , Ductos Biliares/cirurgia , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Glucose and lipid metabolism dysregulation in skeletal muscle contributes to the development of metabolic disorders. The efficacy of fucoxanthin in alleviating lipid metabolic disorders in skeletal muscle remains poorly understood. In this study, we systematically investigated the impact of fucoxanthin on mitigating lipid deposition and insulin resistance in skeletal muscle employing palmitic acid-induced lipid deposition in C2C12 cells and ob/ob mice. Fucoxanthin significantly alleviated PA-induced skeletal muscle lipid deposition and insulin resistance. In addition, fucoxanthin prominently upregulated the expression of lipid metabolism-related genes (Pparα and Cpt-1), promoting fatty acid ß-oxidation metabolism. Additionally, fucoxanthin significantly increased the expression of Pgc-1α and Tfam, elevated the mtDNA/nDNA ratio, and reduced ROS levels. Further, we identified pyruvate kinase muscle isozyme 1 (PKM1) as a high-affinity protein for fucoxanthin by drug affinity-responsive target stability and LC-MS and confirmed their robust interaction by CETSA, microscale thermophoresis, and circular dichroism. Supplementation with pyruvate, the product of PKM1, significantly attenuated the beneficial effects of fucoxanthin on lipid deposition and insulin resistance. Mechanistically, fucoxanthin reduced glucose glycolysis rate and enhanced mitochondrial biosynthesis and fatty acid ß-oxidation through inhibiting PKM1 activity, thereby alleviating lipid metabolic stress. These findings present a novel clinical strategy for treating metabolic diseases using fucoxanthin.
Assuntos
Resistência à Insulina , Metabolismo dos Lipídeos , Músculo Esquelético , Piruvato Quinase , Xantofilas , Animais , Camundongos , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Xantofilas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Piruvato Quinase/metabolismo , Piruvato Quinase/genética , Masculino , Humanos , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversosRESUMO
CONTEXT: Oxidative stress (OS) plays a harmful role in female reproduction and fertility. Several studies explored various dietary interventions and antioxidant supplements, such as astaxanthin (AST), to mitigate the adverse effects of OS on female fertility. Ameliorative effects of AST on female fertility and the redox status of reproductive organs have been shown in several animal and clinical studies. OBJECTIVES: The main objective of present systematic review and meta-analysis of both animal and clinical studies was to provide a comprehensive overview of the current evidence on the effects of AST on female fertility and reproductive outcomes. The effect of AST on redox status, inflammatory and apoptotic markers in reproductive organs were included as the secondary outcomes. DATA SOURCES: We systematically searched electronic databases including PubMed, Scopus, and Web of Science, until January 1, 2024, using specified search terms related to AST, female reproductive performance, and infertility, considering the diverse synonyms found in the literature for interventional studies that compared oral AST supplementation with placebo or control in human or animal models. DATA EXTRACTION: Two independent reviewers extracted data on study characteristics, outcomes, and risk of bias. We pooled the results using random-effects models and assessed the heterogeneity and quality of evidence. We descriptively reported the data from animal models, as meta-analysis was not possible. DATA ANALYSIS: The meta-analysis of clinical trials showed that AST significantly increased the oocyte maturation rate (MD: 8.40, 95% CI: 4.57 to 12.23, I2: 0%) and the total antioxidant capacity levels in the follicular fluid (MD: 0.04, 95% CI: 0.02 to 0.06, I2: 0%). The other ART and pregnancy outcomes and redox status markers did not show statistically significant changes. The animal studies reported ameliorative effects of AST on redox status, inflammation, apoptosis, and ovarian tissue histomorphology. CONCLUSION: This systematic review shows that AST supplementation may improve assisted reproductive technology outcomes by enhancing oocyte quality and reducing OS in the reproductive organs. However, the evidence is limited by the heterogeneity, risk of bias, and small sample size of the included studies.