RESUMO
Oats (Avena sativa L.) are used as therapeutic plants, particularly in dermatology. Despite numerous studies on their skin moisturization, anti-inflammation, and antioxidation effects, the precise molecular mechanisms of these effects are only partially understood. In this study, the efficacy of oat sprouts in the treatment of allergic contact dermatitis (ACD) was investigated, and their specific phytoconstituents and exact mechanisms of action were identified. In the in vivo ACD model, by stimulating the mitogen-activated protein kinase signaling pathway, oat sprouts increased the expression levels of proteins associated with skin barrier formation, which are produced during the differentiation of keratinocytes. In addition, in a lipopolysaccharide-induced skin irritation model using HaCaT, steroidal saponins (avenacoside B and 26-deglucoavenacoside B) and a flavonoid (isovitexin-2-o-arabinoside) of oat sprouts regulated the genetic expression of the same proteins located on the adjacent locus of human chromosomes known as the epidermal differentiation complex (EDC). Furthermore, oat sprouts showed immunomodulatory functions. These findings suggest the potential for expanding the use of oat sprouts as a treatment option for various diseases characterized by skin barrier disruption.
Assuntos
Avena , Extratos Vegetais , Humanos , Avena/genética , Extratos Vegetais/farmacologia , Inflamação , Pele , Anti-Inflamatórios , Grão ComestívelRESUMO
Cold plasma treatment has been studied to enhance the germination, growth, and bioactive phytochemical production in crops. Here, we aimed to investigate the effects of cold plasma treatment on the growth, bioactive metabolite production, and protein expression related to the physiological and osteogenic activities of oat sprouts. Oat seeds were soaked for 12 h, and then exposed to plasma for 6 min/day for 3 days after sowing. Plasma exposure did not significantly change the growth of oat sprouts; however, increased the content of bioactive metabolites. A single exposure for 6 min on the first day (T-1) increased the content of free amino acids (39.4%), γ-aminobutyric acid (53%), and avenacoside B (23%) compared to the control. Hexacosanol content was the highest in T-3 (6 min exposure on each day for 3 days), 28% higher than that in the control. Oat sprout extracts induced the phosphorylation of adenosine 5'-monophosphate-activated protein kinase and osteoblast differentiation was enhanced by increasing the alkaline phosphatase (ALP) activity; all these effects were induced by plasma treatment. Avenacoside B content was positively correlated with ALP activity (r = 0.911, p < 0.1). These results suggest that plasma treatment has the potential to improve the value of oat sprouts and that it may be used in food fortification to enhance nutritional value for promoting human health.
Assuntos
Avena , Gases em Plasma , Humanos , Avena/química , Avena/metabolismo , Gases em Plasma/análise , Gases em Plasma/metabolismo , Germinação , Antioxidantes/farmacologia , Compostos Fitoquímicos/análise , Sementes/químicaRESUMO
Retinal pigment epithelium (RPE) cell dysfunction caused by excessive oxidative damage is partly involved in age-related macular degeneration, which is among the leading causes of visual impairment in elderly people. Here, we investigated the protective role of chrysoeriol against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells. The cellular viability, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were monitored under oxidative stress or pre-treatment with chrysoeriol. The expression levels of mitochondrial-related genes and associated transcription factors were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Moreover, the protein expression of antioxidant signal molecules was characterized by Western blot analysis. Chrysoeriol significantly increased cell viability, reduced ROS generation, and increased the occurrence of antioxidant molecules in H2O2-treated ARPE-19 cells. Additionally, mitochondrial dysfunction caused by H2O2-induced oxidative stress was also considerably diminished by chrysoeriol treatment, which reduced the mitochondrial membrane potential (MMP) and upregulated mitochondrial-associated genes and proteins. Chrysoeriol also markedly enhanced key transcription factors (Nrf2) and antioxidant-associated genes (particularly HO-1 and NQO-1). Therefore, our study confirms the protective effect of chrysoeriol against H2O2-induced oxidative stress in RPE cells, thus confirming that it may prevent mitochondrial dysfunction by upregulating antioxidant-related molecules.
Assuntos
Antioxidantes/farmacologia , Flavonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular , Flavonas/química , Flavonas/isolamento & purificação , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The flavonoid lutonarin (LN) is a component of BS extract and has several known bioactivities. Here, we evaluated LN anti-inflammatory efficacy against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Lutonarin was isolated from BS by methanol extraction and characterized by ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Lutonarin did not reduce the viability or enhance the apoptosis rate of RAW 264.7 macrophages at concentrations up to 150 µM. Concentrations within 20-60 µM dose-dependently suppressed the LPS-induced expression, phosphorylation, and nuclear translocation of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, LN suppressed the LPS-induced upregulation of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α and of the inflammatory enzyme cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Lutonarin may be a safe and effective therapeutic agent for alleviation of pathological inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Glicosídeos/farmacologia , Hordeum/química , Macrófagos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Animais , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2/metabolismo , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/prevenção & controle , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Células RAW 264.7 , Plântula/química , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Seedlings of natural crops are valuable sources of pharmacologically active phytochemicals. In this study, we aimed to identify new active secondary metabolites in Avena sativa L. (oat) seedlings. Two new compounds, avenafuranol (1) and diosgenoside (2), along with eight known compounds (3-10) were isolated from the A. sativa L. seedlings. Their chemical structures were elucidated via 1D and 2D NMR spectroscopy, high-resolution ESIMS, IR spectroscopy, optical rotation analysis, and comparisons with the reported literature. The effect of each isolated compound on alkaline phosphatase (ALP) activity for osteoblast differentiation induced by bone morphogenetic protein-2 (BMP-2) was investigated using the C2C12 immortal mouse myoblast cell line. Compounds 1, 4, 6, 8, and 9 induced dose-dependent increases in ALP expression relative to ALP expression in cells treated with only BMP-2, and no cytotoxicity was observed. These results suggest that A. sativa L. seedlings are a natural source of compounds that may be useful for preventing bone disorders.
Assuntos
Avena/química , Osteoblastos/efeitos dos fármacos , Animais , Avena/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , Plântula/metabolismo , Relação Estrutura-AtividadeRESUMO
Improvement of bone formation is necessary for successful treatment of the bone defects associated with osteoporosis. In this study, we sought to elucidate the osteogenic activity of peanut sprouts and their bioactive components. We found that peanut sprout water extract (PSWE) enhanced bone morphogenetic protein-2-mediated osteoblast differentiation in a dose-dependent manner by stimulating expression of runt-related transcription factor 2 (Runx2) via activation of AKT/MAP kinases. We identified a major component of PSWE, soyasaponin Bb, as the bioactive compound responsible for improvement of anabolic activity. Soyasaponin Bb from PSWE enhanced expression of the osteogenic transcription factor Runx2 and alkaline phosphatase. The soyasaponin Bb content depended on sprouting time of peanut, and the anabolic action of PSWE was dependent on soyasaponin Bb content. Thus, PSWE and soyasaponin Bb have the potential to protect against bone disorders, including osteoporosis.
Assuntos
Arachis/química , Proteínas Morfogenéticas Ósseas/metabolismo , Osteoblastos/metabolismo , Osteogênese/fisiologia , Osteoporose/dietoterapia , Saponinas/metabolismo , Plântula/química , Diferenciação Celular , Proliferação de Células , Osteoporose/patologia , Fatores de TranscriçãoRESUMO
H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7, virB8, and virB10, that are responsible for translocation of CagA into host cells. In particular, menadione inhibited nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation and thereby reduced expression of the proinflammatory cytokines such as IL-1ß, IL-6, IL-8, and TNF-α in AGS as well as in THP-1 (monocytic leukemia cell) cell lines. Collectively, these results suggest the anti-bacterial and anti-inflammatory effects of menadione against H. pylori.
Assuntos
Infecções por Helicobacter/imunologia , Helicobacter pylori/efeitos dos fármacos , NF-kappa B/metabolismo , Vitamina K 3/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Calgranulina A/genética , Calgranulina A/metabolismo , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did not directly interact with the AMPK protein. Instead, saponarin increased intracellular calcium levels and induced AMPK phosphorylation, which was diminished by co-stimulation with STO-609, an inhibitor of CAMKKß. Transcription of hepatic gluconeogenesis genes was upregulated by nuclear translocation of CRTC2 and HDAC5, coactivators of CREB and FoxO1 transcription factors, respectively. This nuclear translocation was inhibited by increased phosphorylation of CRTC2 and HDAC5 by saponarin-induced AMPK in HepG2 cells and suppression of CREB and FoxO1 transactivation activities in cells stimulated by saponarin. The results from a chromatin immunoprecipitation assay confirmed the reduced binding of CRTC2 on the PEPCK and G6Pase promoters. In TE671 cells, AMPK phosphorylated HDAC5, which suppressed nuclear penetration and upregulated GLUT4 transcription, leading to enhanced glucose uptake. Collectively, these results suggest that saponarin activates AMPK in a calcium-dependent manner, thus regulating gluconeogenesis and glucose uptake.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Apigenina/farmacologia , Ativadores de Enzimas/farmacologia , Glucose/metabolismo , Glucosídeos/farmacologia , Benzimidazóis/farmacologia , Compostos de Bifenilo , Cálcio/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Gluconeogênese , Transportador de Glucose Tipo 4/metabolismo , Células Hep G2 , Histona Desacetilases/metabolismo , Humanos , Resistência à Insulina , Metformina/farmacologia , Naftalimidas/farmacologia , Fosforilação , Pironas/farmacologia , Tiofenos/farmacologia , Fatores de Transcrição/metabolismoRESUMO
Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Garcinia mangostana , Neoplasias Pulmonares/tratamento farmacológico , Xantonas/farmacologia , Animais , Caspases/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Citocromos c/metabolismo , Xenoenxertos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Two key virulence factors of Helicobacter pylori are the secreted virulent proteins of vacuolating toxin A (VacA) and cytotoxin associated protein A (CagA) which lead to damages of gastric epithelial cells. We previously identified that the cyanidin 3-O-glucoside (C3G) inhibits the secretion of both VacA and CagA. In the current report, we show that C3G inhibits VacA secretion in a dose-dependent manner by inhibiting secretion system subunit protein A (SecA) synthesis. As SecA is involved in translocation of bacterial proteins, we predicted that inhibition of the SecA pathway by C3G should decrease H. pylori-induced cell death. To test this hypothesis, the human gastric cell line KATO III cells were co-cultured with H. pylori 60190 (VacA(+)/CagA(+)) and C3G. We found that C3G treatment caused a decrease in activation of the pro-apoptotic proteins caspase-3/-8 in H. pylori-infected cells leading to a decrease in cell death. Our data suggest that consumption of foods containing anthocyanin may be beneficial in reducing cell damage due to H. pylori infection.
Assuntos
Antocianinas/administração & dosagem , Proteínas de Bactérias/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Glucosídeos/administração & dosagem , Helicobacter pylori/efeitos dos fármacos , Adenosina Trifosfatases/antagonistas & inibidores , Proteínas de Bactérias/antagonistas & inibidores , Morte Celular/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/microbiologia , Helicobacter pylori/genética , Humanos , Proteínas de Membrana Transportadoras , Canais de Translocação SEC , Proteínas SecA , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Chronic inflammation, which becomes more prevalent during aging, contributes to sarcopenia by reducing muscle mass and strength. PURPOSE: Wheat seedlings extract (WSE) is known for its various physiological activities, including anti-inflammation and antioxidant effects. However, its efficacy against sarcopenia is not well documented. STUDY DESIGN: 8-week-old and 50-week-old C57BL/6 J mice were used as young control (YC group) and aged controls (AC group), respectively. Then, aged mice were randomly divided into 5 groups (WSE100mg/kg, WSE200mg/kg, WSE400mg/kg, and schizandrin as a positive control) and fed each experimental diet for 10 weeks. METHOD: We investigated the effects of WSE on muscle quality and protein homeostasis pathways based on improvements in mitochondrial function and chronic inflammation. We then used TNFα-treated C2C12 to investigate the effects of isoorientin (ISO) and isoschaftoside (ISS), the active substances of WSE, on the myogenic pathway. RESULTS: We administered WSE to aging mice and observed an increase in muscle mass, thickness, protein content, and strength in mice treated with WSE at a dose of 200 mg/kg or 400 mg/kg. Furthermore, the administration of WSE led to a reduction in inflammatory factors (TNFα, IL-1, and IL-6) and an increase in mitochondrial biogenesis (p-AMPK/SIRT3/PGC1α) in muscle. This effect was also observed in TNFα-induced muscle atrophy in C2C12 cells, and we additionally identified the upregulation of myogenic regulatory factors, including Myf5, Myf6, MyoD, and myogenin, by WSE, ISO, and ISS. CONCLUSION: These findings suggest that WSE could function as a dietary anti-inflammatory factor and mitochondrial activator, potentially exerting modulatory effects on the metabolism and mechanical properties of skeletal muscles in the aging population. Furthermore, Our results demonstrate the potential value of ISO and ISS as functional food ingredients for preventing muscle atrophy.
Assuntos
Anti-Inflamatórios , Camundongos Endogâmicos C57BL , Biogênese de Organelas , Extratos Vegetais , Sarcopenia , Plântula , Triticum , Animais , Sarcopenia/tratamento farmacológico , Extratos Vegetais/farmacologia , Anti-Inflamatórios/farmacologia , Masculino , Triticum/química , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Envelhecimento/efeitos dos fármacos , Camundongos , Biossíntese de Proteínas/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Lignanas/farmacologiaRESUMO
Functional flavonoid production is a new agenda in the agricultural industry, and young barley leaves (YBL) are one of the highlighted crops due to their health-beneficial flavonoid, saponarin. For the year-round cultivation of a high saponarin content of YBL, abiotic signal effects on the biosynthesis and metabolism in YBL need to be understood clearly. In this research, the effects of reactive oxygen species (ROS)-related abiotic signals, such as light, potassium, and sodium, were investigated on the biosynthetic metabolism in YBL cultivation under artificial lights. A higher quantity of blue-rich white light (6500 K of light temperature) irradiation enhanced ROS levels and the related enzyme activities (APX and CAT), as well as photosynthesis and saponarin amount, while red-rich white light (3000 K of light temperature) increased the photosynthesis only. In addition, 1.0 g L-1 K+ treatment in water slightly reduced ROS levels and increased saponarin accumulation in YBL. These blue-rich light and K+ supplemental conditions relatively increased OGT expression and reduced 4-coumaric acid and isovitexin as saponarin precursors. Furthermore, the relative ratio of lutonarin as an oxidized product of saponarin increased in increments of light quantity. Finally, the abiotic conditions for saponarin production were optimized with the mixture solution treatment of 1.0 g L-1 Na+ and 1.0 g L-1 K+ under 500 PPFD of 6500 K light, and the saponarin amount per leaf was 219.5 µg plant-1; it was comparable amount with that under sunlight condition.
RESUMO
Saponarin is a functional metabolite produced by barley sprouts, and the mass production of saponarin by this crop is attractive for dietary supplement manufacturing. Light is the most important environmental factor determining plant growth, survival, and the production of secondary metabolites including flavonoids. This study was conducted to investigate the importance of light intensity for saponarin production in barley sprouts using a hydroponic growth system. Light intensity was manipulated by using shielding treatments to 100, 80, 70, and 50% natural sunlight (NS), and crop cultivation was performed on a monthly cycle. We found that the growth rate and biomass of barley sprouts did not differ in response to the shield treatments, whereas the saponarin content did. The highest saponarin content (i.e., from 1329 to 1673 mg 100 g-1) was observed in the 100% NS treatment, and it gradually decreased as light intensity also decreased. Statistical analysis revealed a significant polynomial relationship of saponarin content with cumulative PPFD (R2 = 76%), implying that the absolute total amount of light exposure over the growth period has a large effect on saponarin productivity in a hydroponic facility. Taken together, our results showed that shielding conditions, which are often unintentionally created by the design of cultivation facilities, can adversely affect saponarin production in barley sprouts. In addition, it was confirmed through our findings that light conditions with at least 70% NS in the cultivation facility enable the production of an amount corresponding to the saponarin content of the sprouts (>1000 mg 100 g-1) produced in the open field. Further studies are needed to investigate the underlying physiological and molecular mechanisms responsible for the relationship of saponarin content with light quantity and quality in barley sprouts.
RESUMO
Saponarin (SA) is a major di-C-glycosyl-O-glycosyl flavone, which is predominantly accumulated in the young green leaves of barley (Hordeum vulgare L.), with numerous biological functions in plants, such as protection against environmental stresses. Generally, SA synthesis and its localization in the mesophyll vacuole or leaf epidermis are largely stimulated in response to biotic and abiotic stresses to participate in a plant's defense response. In addition, SA is also credited for its pharmacological properties, such as the regulation of signaling pathways associated with antioxidant and anti-inflammatory responses. In recent years, many researchers have shown the potential of SA to treat oxidative and inflammatory disorders, such as in protection against liver diseases, and reducing blood glucose, along with antiobesity effects. This review aims to highlight natural variations of SA in plants, biosynthesis pathway, and SA's role in response to environmental stress and implications in various therapeutic applications. In addition, we also discuss the challenges and knowledge gaps concerning SA use and commercialization.
RESUMO
Sesame seeds contain several lipids and fragrances that offer health benefits. However, no studies have reported a relationship between the lipids or flavor compounds of sesame seeds and environmental factors. In this study, we aimed to identify this relationship by analyzing the contents of lipidic and flavor compounds in fifteen genotypes of sesame seeds grown in two cultivation regions (Jeonju and Miryang) and years (2018 and 2019). Herein, 17 lipids and 62 flavor compounds were detected. Multivariate statistical analyses revealed that the cultivation year had a larger influence on the contents of lipidic and flavor compounds than the cultivation region and genotype. Furthermore, heat stress due to high cultivation temperature in 2018 caused the accumulation of sugar and secondary metabolites, increased flavor-related substances, and inhibited the degradation of fatty acids. Our study is the first to demonstrate the metabolic changes in lipids and flavor components of sesame in response to environmental temperature changes affected by different cultivation years. Therefore, this study provides guidance for the cultivation of commercially advantageous sesame seeds in improving the quality of sesame seeds and their products.
Assuntos
Sesamum , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/metabolismo , Temperatura , Ácidos Graxos/metabolismo , OdorantesRESUMO
The in vitro effects on melanogenesis of γ-oryzanol (1), a rice bran-derived phytosterol, were investigated. The melanin content in B16F1 cells was significantly and dose-dependently reduced (-13% and -28% at 3 and 30 µM, respectively). Tyrosinase enzyme activity was inhibited by 1 both in a cell-free assay and when analyzed based on the measurement of cellular tyrosinase activity. Transcriptome analysis was performed to investigate the biological pathways altered by 1, and it was found that gene expression involving protein kinase A (PKA) signaling was markedly altered. Subsequent analyses revealed that 1 stimulation in B16 cells reduced cytosolic cAMP concentrations, PKA activity (-13% for cAMP levels and -40% for PKA activity), and phosphorylation of the cAMP-response element binding protein (-57%), which, in turn, downregulated the expression of microphthalmia-associated transcription factor (MITF; -59% for mRNA and -64% for protein), a key melanogenic gene transcription factor. Accordingly, tyrosinase-related protein 1 (TRP-1; -69% for mRNA and -82% for protein) and dopachrome tautomerase (-51% for mRNA and -92% for protein) in 1-stimulated B16F1 cells were also downregulated. These results suggest that 1 has dual inhibitory activities for cellular melanogenesis by inhibiting tyrosinase enzyme activity and reducing MITF and target genes in the PKA-dependent pathway.
Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Melaninas/genética , Monofenol Mono-Oxigenase/metabolismo , Oryza/química , Fenilpropionatos/farmacologia , AMP Cíclico/análise , Oxirredutases Intramoleculares/genética , Melaninas/metabolismo , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Oryza/genética , Fenilpropionatos/químicaRESUMO
Anthocyanins have been studied as potential antimicrobial agents against Helicobacter pylori. We investigated whether the biosynthesis and secretion of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) could be suppressed by anthocyanin treatment in vitro. H. pylori reference strain 60190 (CagA(+)/VacA(+)) was used in this study to investigate the inhibitory effects of anthocyanins; cyanidin 3-O-glucoside (C3G), peonidin 3-O-glucoside (Peo3G), pelargonidin 3-O-glucoside (Pel3G), and malvidin 3-O-glucoside (M3G) on expression and secretion of H. pylori toxins. Anthocyanins were added to bacterial cultures and Western blotting was used to determine secretion of CagA and VacA. Among them, we found that C3G inhibited secretion of CagA and VacA resulting in intracellular accumulation of CagA and VacA. C3G had no effect on cagA and vacA expression but suppressed secA transcription. As SecA is involved in translocation of bacterial proteins, the down-regulation of secA expression by C3G offers a mechanistic explanation for the inhibition of toxin secretion. To our knowledge, this is the first report suggesting that C3G inhibits secretion of the H. pylori toxins CagA and VacA via suppression of secA transcription.
Assuntos
Antocianinas , Antígenos de Bactérias , Proteínas de Bactérias , Glucosídeos , Helicobacter pylori/efeitos dos fármacos , Antocianinas/farmacologia , Antígenos de Bactérias/biossíntese , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , HumanosRESUMO
Momilactone B (MB) is a terpenoid phytoalexin present in rice bran that exhibits several biological activities. MB reduced the melanin content in B16 melanocytes melanin content and inhibited tyrosinase activities. Using transcriptome analysis, the genes involved in protein kinase A (PKA) signaling were found to be markedly altered. B16 cells stimulated with MB had decreased concentrations of cAMP protein kinase A activity, and cAMP-response element-binding protein which is a key transcription factor for microphthalmia-associated transcription factor (MITF) expression. Accordingly, the expression of MITF and its target genes, which are essential for melanogenesis, were reduced. MB thus exhibits anti-melanogenic effects by repressing tyrosinase enzyme activity and inhibiting the PKA signaling pathway which, in turn, decreases melanogenic gene expression.
Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Diterpenos/metabolismo , Oxirredutases Intramoleculares/biossíntese , Lactonas/metabolismo , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Glicoproteínas de Membrana/biossíntese , Oxirredutases/biossíntese , Inibidores de Proteínas Quinases/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Melaninas/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , TranscriptomaRESUMO
A novel liver X receptor (LXR) modulator, iristectorigenin B isolated from Belamcanda chinensis, stimulated the transcriptional activity of both LXR-α and LXR-ß. In macrophages, iristectorigenin B suppressed cholesterol accumulation in a dose-dependent manner and induced the transcriptional activation of LXR-α/-ß-responsive genes, ATP-binding cassette transporters A1 and G1. It did not induce hepatic lipid accumulation nor the expression of the lipogenesis genes sterol regulatory element-binding protein-1c, fatty acid synthase, and stearoyl-CoA desaturase-1. Iristectorigenin B thus is a dual-LXR agonist that regulates the expression of key genes in cholesterol homeostasis in macrophage cells without inducing hepatic lipid accumulation.
Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Expressão Gênica/efeitos dos fármacos , Iridaceae/química , Isoflavonas/metabolismo , Lipoproteínas/biossíntese , Macrófagos/efeitos dos fármacos , Receptores Nucleares Órfãos/agonistas , Transportador 1 de Cassete de Ligação de ATP , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Animais , Linhagem Celular , Isoflavonas/química , Isoflavonas/isolamento & purificação , Receptores X do Fígado , CamundongosRESUMO
Oats and their seeds, stems, and leaves are approved for use as safe food ingredients. Oat seedlings are environmentally friendly and are becoming increasingly popular as they provide several health benefits. We used the UPLC-CAD to quantitatively analyze isolated compounds (1-11) between 15 cultivars of oat seedlings and their harvest time. Maximum average amount of total contents of isolated compounds was observed after the harvest time of 5 days (4711.3 mg/100 g), while the minimum was observed after the harvest time of 7 days (4184.8 mg/100 g). We demonstrated that all isolated compounds (1-11) showed neuraminidase inhibitory effects, with 6 and 7 being the most active with IC50 values of 3.7 and 20.5 µM, respectively. High content of compounds 6 and 7 was observed (2306.6 mg/100 g) in the Dahan cultivar at 9 days, indicating potential good cultivars with a high content of active compounds and neuraminidase inhibition activity.