RESUMO
Polycystic ovarian syndrome (PCOS) is related to pro-apoptotic and pro-inflammatory conditions generated by Endoplasmic reticulum (ER) stress. This study aimed to determine the effect of Astaxanthin (ASX), as carotenoid with potent antioxidant and anti-inflammatory properties, on serum inflammatory markers, apoptotic factors and ER stress-apoptotic genes in peripheral blood mononuclear cells (PBMCs) of women with PCOS. This randomized, double-blind clinical trial included 56 PCOS patients aged 18-40. For 8 weeks, subjects were randomly assigned to one of two groups: either 12 mg ASX (n = 28) or placebo (n = 28). Real-time PCR was used to quantify gene expression associated with ER stress-apoptosis in PCOS women's PBMCs. The levels of TNF-α, IL18, IL6 and CRP were determined by obtaining blood samples from all patients before and after the intervention using Enzyme-linked immunosorbent assay (ELISA). Also, the levels of active caspase-3 and caspase-8 were detected in the PBMC by ELISA kit. Furthermore, we evaluated the efficacy of ASX on disease symptoms. Following the 8-week intervention, ASX supplementation was able to reduce the expression of GRP78 (p = 0.051), CHOP (p = 0.008), XBP1 (p = 0.002), ATF4 (0.038), ATF6 (0.157) and DR5 (0.016) when compared to the placebo. However, this decrease was not statistically significant for ATF6 (p = 0.067) and marginally significant for GRP78 (p = 0.051). The levels of TNF-α (p = 0.009), IL-18 (p = 0.003), IL-6 (p = 0.013) and active caspase-3 (p = 0.012) were also statistically significant lower in the therapy group. However, there was no significant difference in CRP (p = 0.177) and caspase-8 (p = 0.491) levels between the treatment and control groups. In our study, ASX had no significant positive effect on BMI, hirsutism, hair loss and regularity of the menstrual cycle. It appears that ASX may benefit PCOS by changing the ER stress-apoptotic pathway and reducing serum inflammatory markers; however, additional research is required to determine this compound's potential relevance.
Assuntos
Apoptose , Biomarcadores , Suplementos Nutricionais , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Leucócitos Mononucleares , Síndrome do Ovário Policístico , Xantofilas , Humanos , Feminino , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/genética , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/administração & dosagem , Xantofilas/uso terapêutico , Adulto , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Adulto Jovem , Adolescente , Método Duplo-Cego , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Interleucina-18/sangue , Interleucina-18/genética , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/genética , Interleucina-6/sangue , Interleucina-6/genética , Caspase 8/genética , Caspase 8/metabolismoRESUMO
Background: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Cognição , Suplementos Nutricionais , Humanos , Pessoa de Meia-Idade , Método Duplo-Cego , Masculino , Feminino , Cognição/efeitos dos fármacos , Adulto , Idoso , Fator Neurotrófico Derivado do Encéfalo/sangue , Vitamina E , Xantofilas/administração & dosagem , Pele/efeitos dos fármacos , Antioxidantes , Interleucina-6/sangue , Autorrelato , Carotenoides/sangue , Fator de Necrose Tumoral alfa/sangue , Memória de Curto Prazo/efeitos dos fármacos , Memória Episódica , Sucos de Frutas e Vegetais , Malondialdeído/sangue , Olho/efeitos dos fármacosRESUMO
RESEARCH QUESTION: In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients. DESIGN: Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) -6, IL-1ß were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well. RESULTS: A significant decrease in IL-6 and IL-1ß concentrations (both, P = < 0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P = 0.01), the MII oocyte count (P = 0.007), oocyte maturity rate (MII %) (P = 0.02) and number of frozen embryos (P = 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups. CONCLUSIONS: AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings.
Assuntos
Citocinas , Líquido Folicular , Infertilidade Feminina , Estresse Oxidativo , Síndrome do Ovário Policístico , Técnicas de Reprodução Assistida , Xantofilas , Humanos , Feminino , Síndrome do Ovário Policístico/tratamento farmacológico , Xantofilas/farmacologia , Xantofilas/administração & dosagem , Adulto , Citocinas/metabolismo , Gravidez , Infertilidade Feminina/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Líquido Folicular/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/sangue , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Systemic inflammation and oxidation are primary contributors to the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) particles within the vascular endothelium has been hypothesized to be an initial step in the formation of atherosclerotic plaques, with inflammatory cytokines serving as the signaling mechanism for concomitant macrophage activation. Supplementation with the antioxidative macular xanthophylls (lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]) has been shown to aid in the reduction of inflammatory physiologic responses; therefore, we hypothesized that in our study population, supplementation with these xanthophylls would facilitate a systemic reduction in markers of inflammation and cardiovascular lipid oxidation. METHODS AND RESULTS: In this double-blind placebo-controlled supplementation study, participants were randomly allocated to receive the active intervention containing L (10 mg) + MZ (10 mg) + Z (2 mg) or placebo (containing sunflower oil). Serum concentrations of carotenoids (assessed by HPLC), inflammatory cytokines (IL-6, IL-1ß, TNF-α) and oxidized LDL (OxLDL; by solid-phase sandwich ELISA) were measured at baseline and at 6-months. Results showed that over the supplementation period, compared to placebo, the active group demonstrated statistically significant increases in serum concentrations of L, Z, & MZ (p < 0.05), reductions in inflammatory cytokines IL-1ß (p < 0.001) and TNF-α (p = 0.003), as well as a corresponding reduction in serum OxLDL (p = 0.009). CONCLUSIONS: Our data show that L, Z, & MZ supplementation results in decreased serum IL-1ß, TNF-α, and OxLDL. This suggests that these carotenoids are acting systemically to attenuate oxidative lipid products and inflammation, thus reducing their contribution to atherosclerotic plaque formation.
Assuntos
Biomarcadores , Citocinas , Suplementos Nutricionais , Lipoproteínas LDL , Luteína , Estresse Oxidativo , Zeaxantinas , Humanos , Zeaxantinas/sangue , Zeaxantinas/administração & dosagem , Masculino , Método Duplo-Cego , Feminino , Biomarcadores/sangue , Luteína/sangue , Luteína/administração & dosagem , Lipoproteínas LDL/sangue , Pessoa de Meia-Idade , Citocinas/sangue , Adulto , Estresse Oxidativo/efeitos dos fármacos , Mediadores da Inflamação/sangue , Antioxidantes/administração & dosagem , Inflamação/prevenção & controle , Inflamação/sangue , Fator de Necrose Tumoral alfa/sangue , Interleucina-1beta/sangue , Anti-Inflamatórios/administração & dosagem , Xantofilas/administração & dosagem , Xantofilas/sangue , Idoso , Interleucina-6/sangue , Aterosclerose/prevenção & controle , Aterosclerose/sangueRESUMO
A significant clinical condition known as testicular torsion leads to permanent ischemic damage to the testicular tissue and consequent loss of function in the testicles. In this study, it was aimed to evaluate the protective effects of Astaxanthin (ASTX) on testicular damage in rats with testicular torsion/detorsion in the light of biochemical and histopathological data. Spraque Dawley rats of 21 were randomly divided into three groups; sham, testicular torsion/detorsion (TTD) and astaxanthin + testicular torsion/detorsion (ASTX + TTD). TTD and ASTX + TTD groups underwent testicular torsion for 2 hours and then detorsion for 4 hours. Rats in the ASTX + TTD group were given 1 mg/kg/day astaxanthin by oral gavage for 7 days before torsion. Following the detorsion process, oxidative stress parameters and histopathological changes in testicular tissue were evaluated. Malondialdehyde (MDA) and total oxidant status (TOS) levels were significantly decreased in the ASTX group compared to the TTD group, while superoxide dismutase (SOD), glutathione (GSH) and total antioxidant status (TAS) levels were increased (p < 0.05). Moreover, histopathological changes were significantly reduced in the group given ASTX (p < 0.0001). It was determined that ASTX administration increased Beclin-1 immunoreactivity in ischemic testicular tissue, while decreasing caspase-3 immunoreactivity (p < 0.0001). Our study is the first to investigate the antiautophagic and antiapoptotic properties of astaxanthin after testicular torsion/detorsion based on the close relationship of Beclin-1 and caspase-3 in ischemic tissues. Our results clearly demonstrate the protective effects of ASTX against ischemic damage in testicular tissue. In ischemic testicular tissue, ASTX contributes to the survival of cells by inducing autophagy and inhibiting the apoptosis.
Assuntos
Antioxidantes , Autofagia , Estresse Oxidativo , Ratos Sprague-Dawley , Torção do Cordão Espermático , Testículo , Xantofilas , Masculino , Animais , Xantofilas/farmacologia , Xantofilas/administração & dosagem , Autofagia/efeitos dos fármacos , Ratos , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Malondialdeído/metabolismo , Distribuição Aleatória , Traumatismo por Reperfusão/prevenção & controle , Superóxido Dismutase/metabolismo , Glutationa/metabolismoRESUMO
This investigation assessed associations between dietary carotenoid intake and the odds of overweight/obesity, as well as inflammatory/oxidative stress biomarkers, in 851 participants with overweight/obesity (BMI ≥25 kg m-2) and 754 normal-weight controls. A 124-item food-frequency-questionnaire (FFQ) and food composition databases were employed to estimate carotenoid intake. Binary logistic regressions assessed the association of carotenoid intake with the odds of overweight/obesity, adjusting for several potential confounders. Multiple linear regression models revealed associations between carotenoid intake and biomarkers (anthropometrics, blood lipids, inflammation, antioxidant status). Logistic regression models adjusted for various confounders and fruits and vegetables showed protective associations for provitamin A carotenoids (i.e., ß-carotene + α-carotene + ß-cryptoxanthin; odds ratio (OR): 0.655, p = 0.041) and astaxanthin (OR: 0.859, p = 0.017). Similarly adjusted multiple linear regressions revealed significant associations between several carotenoids and lower levels of interleukin (IL)-6, IL-1ß, and TNF-α and increased IL-10 and total antioxidant capacity. Further analysis revealed that lycopene was significantly associated with increased odds of overweight/obesity (OR: 1.595, p = 0.032) in a model adjusted for various confounders and vegetables (i.e., unadjusted for fruits). A protective association between the sum of provitamin A carotenoid and astaxanthin dietary intake and the odds of having overweight/obesity was found. The findings that carotenoids other than lycopene were not or inversely associated with the odds of overweight/obesity may point toward differentiating effects of various carotenoids or their associations with different food groups. Provitamin A rich food items including fruits and vegetables appear to be a prudent strategy to reduce inflammation and the odds of having overweight/obesity.
Assuntos
Biomarcadores , Carotenoides , Inflamação , Obesidade , Sobrepeso , Estresse Oxidativo , Humanos , Carotenoides/administração & dosagem , Feminino , Estresse Oxidativo/efeitos dos fármacos , Masculino , Biomarcadores/sangue , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Inflamação/sangue , Vitamina A/administração & dosagem , Vitamina A/sangue , Provitaminas/administração & dosagem , beta Caroteno/administração & dosagem , Verduras/química , Dieta , Frutas , Xantofilas/administração & dosagem , Xantofilas/farmacologia , beta-Criptoxantina/administração & dosagem , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Interleucina-1beta/sangueRESUMO
BACKGROUND: Astaxanthin is the most prevalent carotenoid in the marine environment and is widely used as an additive in formulated aquafeeds. OBJECTIVES: A 60-day feeding trial was conducted to consider the effect of dietary nanoliposome-coated astaxanthin (NA) on haematological parameters, serum antioxidant activities and immune responses of rainbow trout, Oncorhynchus mykiss. METHODS: A total of 450 healthy fish weighing 31.00 ± 2.09 g were randomly assigned in triplicate (30 fish per replicate) to 5 dietary treatments: 0 (control), 25.00, 50.00, 75.00, and 100.00 mg kg-1 NA. RESULTS: Fish fed the diet supplemented with 50.00 mg kg-1 NA exhibited the highest values of red blood cells, white blood cells, haemoglobin and haematocrit of 1.64 ± 0.01 × 106 mm-3, 5.54 ± 0.21 × 103 mm-3, 8.73 ± 0.24 g dL-1 and 46.67% ± 0.88%, respectively, which were significantly higher than those fed the basal diet (p < 0.05). The lowest and highest percentages of lymphocytes (67.67% ± 0.33%) and neutrophils (27.33% ± 1.20%) were also obtained in fish fed 50.00 mg kg-1 NA compared to those fed the basal diet (p < 0.05). Fish receiving diet supplemented with 50.00 mg kg-1 NA revealed the highest serum activity in superoxide dismutase, catalase, glutathione peroxidase, lysozyme and alternative complement and the lowest level of total cholesterol, cortisol, aspartate aminotransferase and alanine aminotransferase than fish receiving the basal diet (p < 0.05). Serum immunoglobulin (Ig) and ACH50 contents significantly increased with increasing dietary NA supplementation to the highest values of 43.17 ± 1.46 and 293.33 ± 2.03 U mL-1, respectively, in fish fed diet supplemented with 50 mg kg-1 NA (p < 0.05). CONCLUSIONS: Supplementation of NA in rainbow trout diet at 50 mg kg-1 exhibited a positive effect on haematological parameters, antioxidant capacity and immune responses. Administration of such dosage can enhance rainbow trout immune responses against unfavourable or stressful conditions, for example disease outbreaks, hypoxic condition, thermal stress and sudden osmotic fluctuations, which usually happen in an intensive culture system.
Assuntos
Ração Animal , Antioxidantes , Dieta , Suplementos Nutricionais , Oncorhynchus mykiss , Xantofilas , Animais , Xantofilas/administração & dosagem , Xantofilas/farmacologia , Antioxidantes/metabolismo , Dieta/veterinária , Ração Animal/análise , Suplementos Nutricionais/análise , Distribuição Aleatória , Lipossomos , Relação Dose-Resposta a DrogaRESUMO
Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aß) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aß aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aß deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aß neurotoxicity by both degrading FA and reducing FA-induced Aß assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aß oligomerization and extracellular Aß-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Xantofilas , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide , Lipossomos , Camundongos Transgênicos , Fenótipo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Água , Xantofilas/administração & dosagem , Xantofilas/químicaRESUMO
Oxidative stress is a key component of renal ischemia/reperfusion (I/R) injury. Fucoxanthin (Fx), a marine carotenoid with enhanced antioxidant capacity, acts as a ROS inhibitor in diseases such as ischemic stroke and acute lung injury. We hypothesized that fucoxanthin could attenuate renal I/R-induced oxidative damage. C57BL/6 mice (n = 30) were randomly assigned to sham, IR, IR + DMSO, and IR + Fx (25, 50, and 100 mg/kg) groups. The renal I/R injury was induced by clamping the left kidney nephron tip in mice. Fucoxanthin was injected intraperitoneally 24 hours before surgery. Compared with the IR group, pretreatment with fucoxanthin significantly improved renal dysfunction and tissue structural damage and inhibited ROS levels and apoptosis. Consistent results were observed in HK-2 cells. Besides, we found that renal I/R resulted in decreased expression of Sirt1, Nrf2, and HO-1, while fucoxanthin upregulated the expression of Sirt1, Nrf2, and HO-1. The protective effects of fucoxanthin were significantly reversed by EX527 (a selective inhibitor of Sirt1) or si-Sirt1. In conclusion, our study investigated the protective effect of fucoxanthin against renal I/R injury, and the underlying mechanism may be related to the activation of the Sirt1/Nrf2/HO-1 signaling pathway by fucoxanthin to attenuate oxidative stress-induced apoptosis.
Assuntos
Antioxidantes/administração & dosagem , Heme Oxigenase-1/metabolismo , Nefropatias/complicações , Nefropatias/prevenção & controle , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Xantofilas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular/genética , Linhagem Celular , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Nefropatias/metabolismo , Túbulos Renais Proximais/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/genética , Sirtuína 1/genética , Transfecção , Resultado do TratamentoRESUMO
Astaxanthin (AXT) is one of the most important fat-soluble carotenoids that have abundant and diverse therapeutic applications namely in liver disease, cardiovascular disease, cancer treatment, protection of the nervous system, protection of the skin and eyes against UV radiation, and boosting the immune system. However, due to its intrinsic reactivity, it is chemically unstable, and therefore, the design and production processes for this compound need to be precisely formulated. Nanoencapsulation is widely applied to protect AXT against degradation during digestion and storage, thus improving its physicochemical properties and therapeutic effects. Nanocarriers are delivery systems with many advantagesâease of surface modification, biocompatibility, and targeted drug delivery and release. This review discusses the technological advancement in nanocarriers for the delivery of AXT through the brain, eyes, and skin, with emphasis on the benefits, limitations, and efficiency in practice.
Assuntos
Sistemas de Liberação de Medicamentos , Nanoestruturas/administração & dosagem , Nanotecnologia/métodos , Medicina Preventiva , Animais , Humanos , Nanoestruturas/química , Xantofilas/administração & dosagem , Xantofilas/químicaRESUMO
BACKGROUND: Astaxanthin (ASTA) is a kind of food-derived active ingredient (FDAI) with antioxidant and antidiabetic functions. It is nontoxic but its poor solubility and low bioavailability hinder its application in the food industry. In this study, a novel carrier, polyethylene glycol-grafted chitosan (PEG-g-CS) was applied to enhance the bioavailability of astaxanthin. It encapsulated astaxanthin completely by solvent evaporation to manufacture astaxanthin using poly (ethylene glycol)-graft-chitosan nanoparticles (ASTA-PEG-g-CS) nanoparticles to improve absorption. RESULTS: The ASTA-PEG-g-CS nanoparticles were spherical, with a particle size below 200 nm and a ζ potential of about -26 mV. Polyethylene glycol-grafted chitosan can encapsulate astaxanthin well, and the encapsulated astaxanthin was released rapidly - in 15 min in an in vitro release study. In a rat single-pass intestinal perfusion study, a low concentration of ASTA-PEG-g-CS nanoparticle (0.2 µg mL-1 ) was better absorbed in the intestine. In particular, the jejunum could absorb most astaxanthin without a change in the concentration. An in vivo release study also demonstrated that ASTA-PEG-g-CS nanoparticles enhanced oral bioavailability significantly. CONCLUSION: This novel carrier, PEG-g-CS, provided a simple way to encapsulate food, which improved the bioavailability of hydrophobic ingredients. © 2021 Society of Chemical Industry.
Assuntos
Intestinos/metabolismo , Administração Oral , Animais , Disponibilidade Biológica , Quitosana/química , Portadores de Fármacos/química , Composição de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Absorção Intestinal , Masculino , Nanopartículas/química , Tamanho da Partícula , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Xantofilas/administração & dosagem , Xantofilas/química , Xantofilas/farmacocinéticaRESUMO
Fucoxanthin (Fx) has shown potential cancer chemopreventive functions in a carcinogenic murine azoxymethane/dextran sodium sulfate (AOM/DSS) model. However, the molecular mechanisms based on transcriptome profiles in vivo remain poorly understood. We investigated Fx-dependent alterations of the transcriptome with cancer-associated proteins in colorectal mucosal tissue obtained from AOM/DSS mice with or without Fx treatment. Fx administration (50 mg/kg body weight for 14 weeks) significantly prevented the onset of colorectal adenocarcinoma in AOM/DSS mice. A transcriptome analysis revealed that 11 signals, including adhesion, cell cycle, chemokine receptor, interleukin, MAPK, PI3K/AKT, p53, RAS, STAT, TGF-ß, and Wnt were remarkably altered by Fx administration. In particular, chemokine (C-C motif) receptor 1 (Ccr1), which is contained in a gene set related to cytokine-cytokine receptor interactions, was the only significantly down-regulated gene after Fx administration for both 7 and 14 weeks. CCR1, AKT, Cyclin D1, and Smad2 were found to play central roles in the 11 signals shown above. Fx administration significantly down-regulated CCR1 (0.3- and 0.5-fold in mucosal crypts and lamina propria, respectively), pAKT(Ser473) (0.2-fold in mucosal crypts), Cyclin D1 (0.4-fold in mucosal crypts), and pSmad2(Ser465/467) (0.7-fold in mucosal crypts) compared with proteins in these tissues of control mice after Fx administration for 14 weeks. Our findings suggested that Fx exerts a chemopreventive effect in AOM/DSS mice through attenuation of CCR1 expression along with 11 cancer-associated signals.
Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/prevenção & controle , Receptores CCR1/genética , Xantofilas/administração & dosagem , Animais , Azoximetano/efeitos adversos , Quimiocinas CC/metabolismo , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CCR1/metabolismo , Proteína Smad2/genética , Proteína Smad2/metabolismoRESUMO
Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in AT. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor's niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.
Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/fisiologia , Anti-Inflamatórios , Antioxidantes , Suplementos Nutricionais , Tecido Adiposo/patologia , Animais , Citocinas/metabolismo , Glucose/metabolismo , Inflamação , Mediadores da Inflamação/metabolismo , Resistência à Insulina , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Xantofilas/administração & dosagem , Xantofilas/farmacologiaRESUMO
The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, ß-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except ß-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, ß-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.
Assuntos
Antioxidantes/administração & dosagem , Fatores Biológicos/administração & dosagem , Carotenoides/administração & dosagem , Polifenóis/administração & dosagem , Peixe-Zebra/embriologia , terc-Butil Hidroperóxido/efeitos adversos , Animais , Antioxidantes/farmacologia , Apigenina/administração & dosagem , Apigenina/farmacologia , Fatores Biológicos/farmacologia , Carotenoides/farmacologia , Curcumina/administração & dosagem , Curcumina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Flavanonas/administração & dosagem , Flavanonas/farmacologia , Licopeno/administração & dosagem , Licopeno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Xantofilas/administração & dosagem , Xantofilas/farmacologia , beta Caroteno/administração & dosagem , beta Caroteno/efeitos adversos , beta Caroteno/farmacologiaRESUMO
Capsanthin, a brightly orange-red-coloured pigment responsible for the peculiar red colour of paprika fruits (Capsicum annuum), belongs to xanthophylls, a class of oxygen-containing carotenoids. The characteristic chemical structure of capsanthin containing a keto group in conjunction with a long chain of 11 conjugated dienes is responsible for its strong radical scavenging and singlet oxygen quenching ability. Chemopreventive, antitumour, skin photo-protective, anti-inflammatory, and antidiabetic activities demonstrated by capsanthin are a consequence of its potent antioxidant action. Anti-obesity, anti-adipogenic, and antihyperlipidaemic activities are some of the more important features of capsanthin. With natural origin, bright red colour, and array of health benefits, capsanthin has a potential to be translated into a commercial cosmeceutical, nutraceutical, and/or pharmaceutical. However, the very low aqueous solubility of capsanthin is responsible for its highly variable and poor oral bioavailability. Moreover, its susceptibility to degradation due to heat, light, oxygen, and moisture poses challenges in the development of stable formulations for this otherwise meritorious compound. The current review presents various pharmacological activities of capsanthin and their underlying mechanisms. The review further discusses hitherto explored formulation strategies to improve solubility and stability of capsanthin. Graphical abstract.
Assuntos
Animais , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Capsicum/química , Humanos , Hipolipemiantes/administração & dosagem , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Xantofilas/administração & dosagem , Xantofilas/química , Xantofilas/farmacologia , Xantofilas/uso terapêuticoRESUMO
Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.
Assuntos
Asma/tratamento farmacológico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Hipersensibilidade Respiratória/tratamento farmacológico , Xantofilas , Animais , Linhagem Celular , Citocinas/metabolismo , Células Epiteliais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/administração & dosagem , Xantofilas/farmacologiaRESUMO
BACKGROUND/AIM: A xanthophyll of fucoxanthin (Fx) is a potential chemopreventive agent. Familial adenomatous polyposis (FAP) is an inherited disease that is associated with a high risk of developing colorectal cancer. However, it remains unclear whether Fx can modify colorectal tumorigenesis in ApcMin/+ mice, a model mouse for human FAP. MATERIALS AND METHODS: We investigated the chemopreventive effect of Fx in dextran sodium sulfate (DSS)-treated ApcMin/+ mice. RESULTS: Administration of Fx in the diet for 5 weeks significantly suppressed the number of colorectal adenocarcinomas in DSS-treated male ApcMin/+ mice, although the treatment did not affect the occurrence of colorectal dysplastic crypts and adenoma in the mice. In addition, Fx down-regulated cyclin D1 expression (0.6-fold) in colorectal mucosa of ApcMin/+ mice when compared with that of the control mice. CONCLUSION: Fx possesses chemopreventive potential against progression of colorectal carcinogenesis in ApcMin/+ mice that receive inflammatory stimuli.
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Polipose Adenomatosa do Colo/complicações , Anticarcinógenos/administração & dosagem , Neoplasias Colorretais/prevenção & controle , Xantofilas/administração & dosagem , Animais , Neoplasias Colorretais/induzido quimicamente , Ciclina D1/análise , Ciclina D1/fisiologia , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , CamundongosRESUMO
Fucoxanthin (Fx), a marine carotenoid found in edible brown algae, is well known for having anticancer properties. The gut microbiota has been demonstrated as a hallmark for colorectal cancer progression in both humans and rodents. However, it remains unclear whether the gut microbiota is associated with the anticancer effect of Fx. We investigated the chemopreventive potency of Fx and its effect on gut microbiota in a mouse model of inflammation-associated colorectal cancer (by azoxymethane/dextran sulfate sodium treatment). Fx administration (30 mg/kg bw) during a 14 week period significantly inhibited the multiplicity of colorectal adenocarcinoma in mice. The number of apoptosis-like cleaved caspase-3high cells increased significantly in both colonic adenocarcinoma and mucosal crypts. Fx administration significantly suppressed Bacteroidlales (f_uc; g_uc) (0.3-fold) and Rikenellaceae (g_uc) (0.6-fold) and increased Lachnospiraceae (g_uc) (2.2-fold), compared with those of control mice. Oral administration of a fecal suspension obtained from Fx-treated mice, aimed to enhance Lachnospiraceae, suppress the number of colorectal adenocarcinomas in azoxymethane/dextran sulfate sodium-treated mice with a successful increase in Lachnospiraceae in the gut. Our findings suggested that an alteration in gut microbiota by dietary Fx might be an essential factor in the cancer chemopreventive effect of Fx in azoxymethane/dextran sulfate sodium-treated mice.
Assuntos
Adenocarcinoma/prevenção & controle , Colite Ulcerativa/tratamento farmacológico , Neoplasias Associadas a Colite/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Xantofilas/administração & dosagem , Adenocarcinoma/imunologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Animais , Azoximetano/administração & dosagem , Azoximetano/toxicidade , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Neoplasias Associadas a Colite/imunologia , Neoplasias Associadas a Colite/microbiologia , Neoplasias Associadas a Colite/patologia , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Fezes/microbiologia , Microbioma Gastrointestinal/imunologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , CamundongosRESUMO
Astaxanthin (AST) and fucoxanthin (FUC) are natural xanthophylls, having multidirectional activity, including antioxidant, anti-inflammatory, and anticancer. Both compounds also show antimicrobial activity, which is presented in this review article. There are few papers that have presented the antimicrobial activity of AST. Obtained antimicrobial concentrations of AST (200-4000 µg/mL) are much higher than recommended by the European Food Safety Authority for consumption (2 mg daily). Therefore, we suggest that AST is unlikely to be of use in the clinical treatment of infections. Our knowledge about the antimicrobial activity of FUC is better and this compound acts against many bacteria already in low concentrations 10-250 µg/mL. Toxicological studies on animals present the safety of FUC application in doses 200 mg/kg body weight and higher. Taking available research into consideration, a clinical application of FUC as the antimicrobial substance is real and can be successful. However, this aspect requires further investigation. In this review, we also present potential mechanisms of antibacterial activity of carotenoids, to which AST and FUC belong.
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Antibacterianos/administração & dosagem , Xantofilas/administração & dosagem , Animais , Organismos Aquáticos , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade MicrobianaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Laminaria japonica, a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including lung cancer. AIM OF THE STUDY: To demonstrate the effects of Fucoxanthin (FX), a major active component extracted from Laminaria japonica on metastasis and Gefitinib (Gef) sensitivity in human lung cancer cells both in vitro and in vivo. MATERIALS AND METHODS: Invasion and migration of lung cancer cells were detected using the wound healing assay and transwell assay. Epithelial-to-mesenchymal transition (EMT) factors and PI3K/AKT/NF-κB pathways were analyzed by western blotting. RNA interference (RNAi) technology was used to silence TIMP-2 gene expression in A549 cells. The anti-metastatic effect of FX was evaluated in vivo in an experimental lung metastatic tumor model. On the other hand, cell counting kit-8 assay was used to study the cell viability of human lung cancer PC9 cells and Gef resistant PC9 cells (PC9/G) after Gef, FX or FX combined with Gef treatment. PC9 xenograft model was established to explore the anti-tumor effect of FX or combined with Gef. Immunohistochemistry staining assay and immunofluorescence staining assay were used to reveal the effects of FX on lung cancer cell proliferation and apoptosis. RESULTS: FX was able to significantly inhibit lung cancer cells migration and invasion in vitro. FX suppressed the expressions of Snail, Twist, Fibronectin, N-cadherin, MMP-2, PI3K, p-AKT and NF-κB, and increased the expression of TIMP-2. Furthermore, knockdown of TIMP-2 attenuated FX-mediated invasion inhibition. Additionally, we demonstrated that FX inhibited lung cancer cells metastasis in vivo. The anti-metastatic effects of FX on lung cancer cells might be attributed to inhibition of EMT and PI3K/AKT/NF-κB pathway. We further demonstrated that the anti-tumor activity of FX was not only limited to the drug sensitive cell lines, but also prominent on lung cancer cells with Gef resistant phenotype. Furthermore, in vivo xenograft assay confirmed that FX inhibited tumor growth and enhanced the sensitivity of lung cancer cells to Gef and this effect may be due to inhibition of tumor cell proliferation and activation of apoptosis. CONCLUSION: Collectively, our findings suggested that FX suppresses metastasis of lung cancer cells and overcomes EGFR TKIs resistance. Thus, FX is worthy of further investigation as a drug candidate for the treatment of lung cancer.