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In this investigation, the photophysical properties and interaction mechanisms of Janus green blue (JGB) dye with polyanions were systematically studied using spectroscopic techniques. The absorption spectral analysis revealed that JGB binds cooperatively to sodium alginate, leading to dye stacking along the polymer chain. The interaction of JGB dye with DNA was characterized by the emergence of a metachromatic peak at 564 nm, indicating the formation of dye aggregates. The analysis of absorption data reveals that JGB dye interacts with DNA at multiple binding sites, including at least one high-affinity site. The AutoDock Vina based blind docking approach was used to analyze the most probable binding location of JGB dye in DNA. By making use of the DNA-induced metachromasia, a colorimetric approach was developed for the visualization of loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR). The LAMP-colorimetric assay, targeting the Streptococcus pneumoniae gene, demonstrated a noticeable colour change with a detection limit of 1 pg µL-1. The practical applicability was validated by detecting S. pneumoniae in artificial urine. In addition to LAMP, we tested the JGB dye based colorimetric assay for applicability in PCR reactions. The colorimetric PCR assay using the metal-responsive transcription factor (MTF-1) gene achieved a detection limit as low as 0.1 pg µL-1. The study highlights the potential of DNA binding metachromic dye to significantly enhance colorimetric assays, offering a robust and sensitive tool for molecular diagnostics.
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Nanoplastics (NPs), plastic particles ranging from 1 to 100 nm are ubiquitous environmental pollutants infiltrating ecosystems. Their small size and widespread use in various products raise concerns for human health, particularly their association with cardiovascular diseases (CVD). NPs can enter the human body through multiple routes, causing oxidative stress, and leading to the senescence and dysfunction of endothelial cells (ECs). Although there are potential natural compounds for treating CVD, there is limited research on preventing CVD induced by NPs. This study investigates the efficacy of Ecklonia cava extract (ECE) in preventing NPs-induced premature vascular senescence and dysfunction. Exposure of porcine coronary arteries (PCAs) and porcine coronary ECs to NPs, either alone or in combination with ECE, demonstrated that ECE mitigates senescence-associated ß-galactosidase (SA-ß-gal) activity induced by NPs, thus preventing premature endothelial senescence. ECE also improved NPs-induced vascular dysfunction. The identified active ingredient in Ecklonia cava, 2,7'-Phloroglucinol-6,6'-bieckol (PHB), a phlorotannin, proved to be pivotal in these protective effects. PHB treatment ameliorated SA-ß-gal activity, reduced oxidative stress, restored cell proliferation, and decreased the expression of cell cycle regulatory proteins such as p53, p21, p16, and angiotensin type 1 receptor (AT1), well known triggers for EC senescence. Moreover, PHB also improved NPs-induced vascular dysfunction by upregulating endothelial nitric oxide synthase (eNOS) expression and restoring endothelium-dependent vasorelaxation. In conclusion, Ecklonia cava and its active ingredient, PHB, exhibit potential as therapeutic agents against NPs-induced premature EC senescence and dysfunction, indicating a protective effect against environmental pollutants-induced CVDs associated with vascular dysfunction.
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Senescencia Celular , Dioxinas , Phaeophyceae , Senescencia Celular/efectos de los fármacos , Animales , Porcinos , Células Endoteliales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Floroglucinol/farmacología , Floroglucinol/análogos & derivados , NanopartículasRESUMEN
In the present investigation, 24-methylcholesta-5(6), 22-diene-3ß-ol (MCDO), a major phytosterol was isolated from the cultured marine diatom, Phaeodactylum tricornutum Bohlin, and in vitro and in vivo anti-inflammatory effects were determined. MCDO demonstrated very potent dose-dependent inhibitory effects on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) against lipopolysaccharide (LPS)-induced RAW 264.7 cells with minimal cytotoxic effects. MCDO also demonstrated a strong and significant suppression of pro-inflammatory cytokines of interleukin-1ß (IL-1ß) production, but no substantial inhibitory effects were observed on the production of cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at the tested concentrations against LPS treatment on RAW macrophages. Western blot assay confirmed the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions against LPS-stimulated RAW 264.7 cells. In addition, MCDO was assessed for in vivo anti-inflammatory effects using the zebrafish model. MCDO acted as a potent inhibitor for reactive oxygen species (ROS) and NO levels with a protective effect against the oxidative stress induced by LPS in inflammatory zebrafish embryos. Collectively, MCDO isolated from the cultured marine diatom P. tricornutum exhibited profound anti-inflammatory effects both in vitro and in vivo, suggesting that this major sterol might be a potential treatment for inflammatory diseases.
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Diatomeas , Animales , Diatomeas/metabolismo , Pez Cebra/metabolismo , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Transducción de Señal , Citocinas/metabolismo , Interleucina-6/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ciclooxigenasa 2/metabolismoRESUMEN
Oxylipins are important biological molecules with diverse roles in human and plants such as pro-/anti-inflammatory, antimicrobial, and regulatory activity. Although there is an increasing number of plant-derived oxylipins, most of their physiological roles in humans remain unclear. Here, we describe the isolation, identification, and biological activities of four new oxylipins, chaenomesters A-D (1-4), along with a known compound (5), obtained from Chaenomeles sinensis twigs. Their chemical structures were determined by spectroscopic (i.e., NMR) and spectrometric (i.e., HRMS) data analysis including 1H NMR-based empirical rules and homonuclear-decoupled 1H NMR experiments. Chaenomester D (4), an omega-3 oxylipin, showed a potent inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells (NO production, 8.46 ± 0.68 µM), neurotrophic activity in C6 cells through the induction of the secretion of nerve growth factor (NGF, 157.7 ± 2.4%), and cytotoxicity in A549 human cancer cell lines (IC50 = 27.4 µM).
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Skeletal muscle is an important tissue in energy metabolism and athletic performance. The use of effective synthetic supplements and drugs to promote muscle growth is limited by various side effects. Moreover, their use is prohibited by anti-doping agencies; hence, natural alternatives are needed. Therefore, we evaluated the muscle growth effect of substances that can act like synthetic supplements from edible marine algae. First, we isolated six marine algal polyphenols belonging to the phlorotannin class, namely dieckol (DK), 2,7â³-phloroglucinol-6,6'-bieckol (PHB), phlorofucofuroeckol A (PFFA), 6,6'-bieckol (6,6-BK), pyrogallol-phloroglucinol-6,6'-bieckol (PPB), and phloroglucinol (PG) from an edible brown alga, Ecklonia cava and evaluated their effects on C2C12 myoblasts proliferation and differentiation. Of the six phlorotannin isolates evaluated, DK and PHB induced the highest degree of C2C12 myoblast proliferation. In addition, DK and PHB regulates myogenesis by down-regulating the Smad signaling, a negative regulator, and up-regulating the insulin-like growth factor-1 (IGF-1) signaling, a positive regulator. Interestingly, DK and PHB bind strongly to myostatin, which is an inhibitor of myoblast proliferation, while also binding to IGF-1 receptors. Moreover, they bind to IGF-1 receptor. These results suggest that DK and PHB are potential natural muscle building supplements and could be a safer alternative to synthetic drugs.
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Organismos Acuáticos/química , Cianobacterias/química , Factor I del Crecimiento Similar a la Insulina/metabolismo , Músculo Esquelético/crecimiento & desarrollo , Polifenoles/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Smad/metabolismo , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Forma MM de la Creatina-Quinasa/metabolismo , Ratones , Simulación del Acoplamiento Molecular , Células Musculares/efectos de los fármacos , Desarrollo de Músculos/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Miostatina/química , Miostatina/metabolismo , Prohibitinas , Receptor IGF Tipo 1/química , Receptor IGF Tipo 1/metabolismoRESUMEN
Saringosterol acetate (SSA) was isolated from an edible brown alga Hizikia fusiforme. In this study, we developed an adult zebrafish human hepatocellular carcinoma (HCC) xenograft model to confirm that SSA inhibits tumor growth and metastasis. Established Hep3B cells labeled with the fluorescent tracker CM-Dil were xenografted into the abdominal cavity of zebrafish once every three days for one month. Compared with the control group, the fish injected with Hep3B showed a significant increase in α-fetoprotein (AFP) and factors related to tumor growth and metastasis (IL-6, TNF-α, TGFß, MMP2, and MMP9). Using the model, it was proven that SSA affected survival rate, AFP production, and the levels of factors related to tumor growth and metastasis via the PI3K/AKT/mTOR and TGFß/Smad pathways. In conclusion, this HCC model can be used for in vivo experiments to investigate the inhibition of cancer, and SSA may be useful for the treatment of cancer.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Sargassum/química , Estigmasterol/análogos & derivados , Estigmasterol/uso terapéutico , Animales , Línea Celular Tumoral , Femenino , Humanos , Masculino , Metástasis de la Neoplasia/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Pez CebraRESUMEN
Transcriptional coactivator with PDZ-binding motif (TAZ) plays crucial role in maintaining testicular structure and function via regulation of senescence of spermatogenic cells. However, it remains unclear whether TAZ is involved in testosterone biosynthesis in testicular Leydig cells. We found that TAZ deficiency caused aberrant Leydig cell expansion and increased lipid droplet formation, which was significantly associated with increased lipogenic enzyme expression. Additionally, the expression of key steroidogenic enzymes, including steroidogenic acute regulatory protein, cytochrome P450 (CYP) 11A1, CYP17A1, and 3ß-hydroxysteroid dehydrogenase, was greatly increased in TAZ-deficient testes and primary Leydig cells. Interestingly, the transcriptional activity of nuclear receptor 4 A1 (NR4A1) was dramatically suppressed by TAZ; however, the protein expression and the subcellular localization of NR4A1 were not affected by TAZ. TAZ directly associated with the N-terminal region of NR4A1 and substantially suppressed its DNA-binding and transcriptional activities. Stable expression of TAZ in the mouse Leydig TM3 cell line decreased the expression of key steroidogenic enzymes, whereas knockdown of endogenous TAZ in TM3 cells increased transcripts of steroidogenic genes induced by NR4A1. Consistently, testosterone production was enhanced within TAZ-deficient Leydig cells. However, TAZ deficiency resulted in decreased testosterone secretion caused by dysfunctional mitochondria and lysosomes. Therefore, TAZ plays essential role in NR4A1-induced steroidogenic enzyme expression and testosterone production in Leydig cells.
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17-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , Células Intersticiales del Testículo/metabolismo , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Fosfoproteínas/antagonistas & inhibidores , Esteroide 17-alfa-Hidroxilasa/antagonistas & inhibidores , Testosterona/metabolismo , Transactivadores/fisiología , 17-Hidroxiesteroide Deshidrogenasas/genética , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Esteroide 17-alfa-Hidroxilasa/genética , Esteroide 17-alfa-Hidroxilasa/metabolismoRESUMEN
Chronic alcohol feeding increases the levels of 2-arachidonoylglycerol (2-AG) in the liver, which activates hepatic cannabinoid receptor type 1 (CB1R), leading to oxidative liver injury. 2-AG biosynthesis is catalyzed by diacylglycerol lipase (DAGL). However, the mechanisms regulating hepatic DAGL gene expression and 2-AG production are largely unknown. In this study, we show that CB1R-induced estrogen-related receptor γ (ERRγ) controls hepatic DAGL gene expression and 2-AG levels. Arachidonyl-2'-chloroethylamide (ACEA), a synthetic CB1R agonist, significantly upregulated ERRγ, DAGLα, and DAGLß, and increased 2-AG levels in the liver (10 mg/kg) and hepatocytes (10 µM) of wild-type (WT) mice. ERRγ overexpression upregulated DAGLα and DAGLß expressions and increased 2-AG levels, whereas ERRγ knockdown abolished ACEA-induced DAGLα, DAGLß, and 2-AG in vitro and in vivo. Promoter assays showed that ERRγ positively regulated DAGLα and DAGLß transcription by binding to the ERR response element in the DAGLα and DAGLß promoters. Chronic alcohol feeding (27.5% of total calories) induced hepatic steatosis and upregulated ERRγ, leading to increased DAGLα, DAGLß, or 2-AG in WT mice, whereas these alcohol-induced effects did not occur in hepatocyte-specific CB1R knockout mice or in those treated with the ERRγ inverse agonist GSK5182 (40 mg/kg in mice and 10 µM in vitro). Taken together, these results indicate that suppression of alcohol-induced DAGLα and DAGLß gene expressions and 2-AG levels by an ERRγ-specific inverse agonist may be a novel and attractive therapeutic approach for the treatment of alcoholic liver disease.
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Ácidos Araquidónicos/biosíntesis , Ácidos Araquidónicos/farmacología , Endocannabinoides/biosíntesis , Etanol/toxicidad , Glicéridos/biosíntesis , Lipoproteína Lipasa/genética , Receptores de Estrógenos/metabolismo , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Lipoproteína Lipasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor Cannabinoide CB1/agonistas , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismo , Receptores de Estrógenos/genética , Tamoxifeno/análogos & derivados , Tamoxifeno/farmacologíaRESUMEN
Extract of the Japanese apricot (JAE) has biological properties as an antioxidant and anti-inflammatory agent. We hypothesized that JAE might exert therapeutic effects on cigarette smoke (CS)-induced DNA damage and cytotoxicity. In this study, we found that concentrated JAE protects against cigarette smoke extract (CSE)-induced cytotoxicity and DNA damage accompanied by increased levels of aldehyde dehydrogenase (ALDH)2, 3A1, and Werner's syndrome protein (WRN) in immortalized human bronchial epithelial cells (HBEC2) and normal human epidermal keratinocytes (NHEK). Using the centrifugal partition chromatography (CPC) method, we identified an undescribed compound, 5-hydroxymethyl-2-furaldehyde bis(5-formylfurfuryl) acetal (which we named FA-1), responsible for the protective effects against CSE. This chemical structure has not been reported from a natural source to date. Protective effects of isolated FA-1 against CSE were observed in both HBEC2 and NHEK cells. The studies described herein suggest that FA-1 isolated from JAE protects against CSE-induced DNA damage and apoptosis by augmenting multiple isozymes of ALDH and DNA repair and reducing oxidative stress.
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Bronquios/efectos de los fármacos , Fumar Cigarrillos/efectos adversos , Extractos Vegetales/farmacología , Aldehído Deshidrogenasa , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Bronquios/citología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Furaldehído/análogos & derivados , Humanos , Inflamación/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Prunus/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Humo/efectos adversos , Nicotiana/químicaRESUMEN
Impaired function and decreasing numbers of pancreatic ß cells are key factors in the development of type 2 diabetes. This study investigated whether 2,7â³-phloroglucinol-6,6'-bieckol protects INS-1 cells against high glucose-induced glucotoxicity and apoptosis. High glucose (30â¯mM) treatment led to glucotoxicity and induced apoptosis in INS-1 cells. However, treatment with 10-50⯵M 2,7â³-phloroglucinol-6,6'-bieckol significantly reduced glucotoxicity (22.4%) and increased cell viability (up to 80.9%). Treatment with 2,7â³-phloroglucinol-6,6'-bieckol caused a dose-dependent decrease in intracellular reactive oxygen species, lipid peroxidation, and nitric oxide levels, which are increased in INS-1 cells exposed to high glucose. The level of intracellular reactive oxygen species, lipid peroxidation, and nitric oxide levels in INS-1 cells treated with 30â¯mM glucose and 50⯵M 2,7â³-phloroglucinol-6,6'-bieckol (101.9%, 0.11 % and 102.1%) was similar to that of the control group (100%). Furthermore, 2,7â³-phloroglucinol-6,6'-bieckol significantly reduced the levels of pro-apoptotic Bax, caspase 9, and caspase 3 proteins, and increased the levels of the anti-apoptotic Bcl-2 protein and poly ADP-ribose polymerase. The Bcl-2/Bax ratio was 6-fold higher in 50⯵M 2,7â³-phloroglucinol-6,6'-bieckol-treated INS-1 cells than in untreated cells. Apoptotic cells were identified using annexin V/propidium iodide staining, and cells treated with 50⯵M 2,7â³-phloroglucinol-6,6'-bieckol, the numbers of late apoptotic cells decreased over 2-fold compared to that observed in cells treated with 30â¯mM glucose. Overall, these results suggest that 2,7â³-phloroglucinol-6,6'-bieckol has the potential for use as a pharmaceutical agent to protect pancreatic ß cells against high glucose-induced apoptosis.
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Apoptosis/efectos de los fármacos , Dioxanos/farmacología , Glucosa/toxicidad , Floroglucinol/análogos & derivados , Sustancias Protectoras/farmacología , Caspasas/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocromos c/metabolismo , Dioxanos/química , Humanos , Insulina/metabolismo , Secreción de Insulina , Espacio Intracelular/metabolismo , Óxido Nítrico/metabolismo , Floroglucinol/química , Floroglucinol/farmacología , Sustancias Protectoras/química , Especies Reactivas de Oxígeno/metabolismo , Coloración y Etiquetado , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
The present study was performed to investigate the anti-inflammatory activity of Tetragonia tetragonoides hydrosols (TTH) and its underlying mechanism in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Gas chromatography (GC) coupled with mass spectrometry and retention index calculations showed that TTH were mainly composed of tetratetracontane (29.5 %), nonacosane (27.6 %), and oleamide (17.1 %). TTH significantly decreased the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-6, and IL-1ß in LPS-stimulated RAW 264.7 cells. Consistent with these observations, TTH treatment decreased the protein expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). The molecular mechanism of its anti-inflammatory activity was found to be associated with inhibition of nuclear factor-kappa B (NF-κB) phosphorylation and nuclear translocation of NF-κB 65. Furthermore, TTH markedly suppressed the LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs). Taken together, these data indicate that TTH exerts an anti-inflammatory activity by inhibiting the NF-κB and MAPK signaling pathways in LPS-stimulated RAW 264.7 cells.
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In this study, we investigated the effect and mechanism of Undariopsis peterseniana, an edible brown alga, on hair growth. The treatment of vibrissa follicles with U. peterseniana extract ex vivo for 21 days significantly increased the hair-fiber lengths. The U. peterseniana extract also significantly accelerated anagen initiation in vivo. Moreover, we found that U. peterseniana extract was able to open the KATP channel, which may contribute to increased hair growth. The U. peterseniana extract decreased 5α-reductase activity and markedly increased the proliferation of dermal papilla cells, a central regulator of the hair cycle. The U. peterseniana extract increased the levels of cell cycle proteins, such as Cyclin D1, phospho(ser780)-pRB, Cyclin E, phospho-CDK2, and CDK2. The U. peterseniana extract also increased the phosphorylation of ERK and the levels of Wnt/ß-catenin signaling proteins such as glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin. These results suggested that the U. peterseniana extract had the potential to influence hair growth by dermal papilla cells proliferation through the activation of the Wnt/ß-catenin and ERK pathways. We isolated a principal of the U. peterseniana extract, which was subsequently identified as apo-9'-fucoxanthinone, a trichogenic compound. The results suggested that U. peterseniana extract may have a pivotal role in the treatment of alopecia.
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Proliferación Celular/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Cabello/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Phaeophyceae/química , Terpenos/farmacología , Vía de Señalización Wnt/efectos de los fármacos , Animales , Productos Biológicos/farmacología , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Femenino , Cabello/metabolismo , Folículo Piloso/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
CONTEXT: 2,7â³-Phloroglucinol-6,6'-bieckol is a type of phlorotannin isolated from brown algae, Ecklonia cava Kjellman (Phaeophyceae; Laminareaceae). 2,7â³-Phloroglucinol-6,6'-bieckol mediates antioxidant activities. However, there has been no research on improving postprandial hyperglycaemia using 2,7â³-phloroglucinol-6,6'-bieckol. OBJECTIVE: This study investigated the inhibitory effects of 2,7â³-phloroglucinol-6,6'-bieckol on activities of α-glucosidase and α-amylase as well as its alleviating effect on postprandial hyperglycaemia in streptozotocin-induced diabetic mice. MATERIALS AND METHODS: α-Glucosidase and α-amylase inhibitory assays were carried out. The effect of 2,7â³-phloroglucinol-6,6'-bieckol on hyperglycaemia after a meal was measured by postprandial blood glucose in streptozotocin-induced diabetic and normal mice. The mice were treated orally with soluble starch (2 g/kg BW) alone (control) or with 2,7â³-phloroglucinol-6,6'-bieckol (10 mg/kg bw) or acarbose (10 mg/kg BW) dissolved in 0.2 mL water. Blood samples were taken from tail veins at 0, 30, 60, and 120 min and blood glucose was measured by a glucometer. RESULTS: 2,7â³-Phloroglucinol-6,6'-bieckol showed higher inhibitory activities than acarbose, a positive control against α-glucosidase and α-amylase. The IC50 values of 2,7â³-phloroglucinol-6,6'-bieckol against α-glucosidase and α-amylase were 23.35 and 6.94 µM, respectively, which was found more effective than observed with acarbose (α-glucosidase IC50 of 130.04 µM; α-amylase IC50 of 165.12 µM). In normal mice, 2,7â³-phloroglucinol-6,6'-bieckol significantly suppressed the postprandial hyperglycaemia caused by starch. The 2,7â³-phloroglucinol-6,6'-bieckol administration group (2349.3 mmol·min/L) had a lower area under the curve (AUC) glucose response than the control group (2690.83 mmol·min/L) in diabetic mice. DISCUSSION AND CONCLUSION: 2,7â³-Phloroglucinol-6,6'-bieckol might be used as an inhibitor of α-glucosidase and α-amylase as well as to delay absorption of dietary carbohydrates.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Dioxanos/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Phaeophyceae/química , Floroglucinol/análogos & derivados , Células 3T3-L1 , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Dioxanos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Masculino , Ratones , Ratones Endogámicos ICR , Floroglucinol/aislamiento & purificación , Floroglucinol/farmacología , Periodo Posprandial , Estreptozocina , Factores de Tiempo , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , alfa-Glucosidasas/metabolismoRESUMEN
This study describes a simple preparation of functional polysaccharides from Pyropia yezoensis using a microwave-assistant rapid enzyme digest system (MAREDS) with various carbohydrases, and evaluates their antioxidative effects. Polysaccharide hydrolysates were prepared using MAREDS under different hydrolytic conditions of the carbohydrases and microwave powers. Polysaccharides less than 10kDa (Low molecular weight polysaccharides, LMWP, ≤10kDa) were efficiently obtained using an ultrafiltration (molecular weight cut-off of 10kDa). MAREDS increases AMG activation via an increased degree of hydrolysis; the best AMG hydrolysate was prepared using a 10:1 ratio of substrate to enzyme for 2h in MAREDS with 400W. LMWP consisted of galactose (27.3%), glucose (64.5%), and mannose (8.3%) from the AMG hydrolysate had stronger antioxidant effects than the high molecular weight polysaccharides (>10kDa). We rapidly prepared functional LMWPs by using MAREDS with carbohydrases, and suggest that LMWP might be potentially a valuable algal polysaccharide antioxidant.
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Antioxidantes/química , Polisacáridos/química , Rhodophyta/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Fraccionamiento Químico , Microondas , Monosacáridos/química , Monosacáridos/aislamiento & purificación , Monosacáridos/farmacología , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , UltrafiltraciónRESUMEN
Long-term cigarette smoking increases the risk for chronic obstructive pulmonary disease (COPD), characterized by irreversible expiratory airflow limitation. The pathogenesis of COPD involves oxidative stress and chronic inflammation. Various natural marine compounds possess both anti-oxidant and anti-inflammatory properties, but few have been tested for their efficacy in COPD models. In this study, we conducted an in vitro screening test to identify natural compounds isolated from various brown algae species that might provide protection against cigarette smoke extract (CSE)-induced cytotoxicity. Among nine selected natural compounds, apo-9'-fucoxanthinone (Apo9F) exhibited the highest protection against CSE-induced cytotoxicity in immortalized human bronchial epithelial cells (HBEC2). Furthermore, the protective effects of Apo9F were observed to be associated with a significant reduction in apoptotic cell death, DNA damage, and the levels of mitochondrial reactive oxygen species (ROS) released from CSE-exposed HBEC2 cells. These results suggest that Apo9F protects against CSE-induced DNA damage and apoptosis by regulating mitochondrial ROS production.
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Apoptosis/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Nicotiana/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Rhodophyta/química , Humo/efectos adversos , Terpenos/farmacología , Línea Celular , Daño del ADN/efectos de los fármacos , Células Epiteliales/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fumar/efectos adversos , Terpenos/químicaRESUMEN
We investigated anticancer effects of the crude polysaccharides (CPs) isolated from Ecklonia cava enzymatic extracts using AMG, Viscozyme, Protamex, and Alcalase enzyme against a colon cancer cell line, CT26 cells. Among them, the CP of Protamex extract (PCP) contained the highest fucose and sulfated group contents and showed the highest growth inhibitory effect against CT-26 cells. In addition, PCP dose-dependently increased the formation of apoptotic body and the percentage of Sub-G1 DNA contents. Also, PCP activated caspase 9 and PARP as regulating the expressions of Bax and Bcl-2. Moreover, PPP2, a fraction purified from PCP showed the highest growth inhibitory effect against CT 26 cells with the increased fucose and sulfated group contents. The results demonstrate that the isolated SP containing plentiful fucose and sulfated group contents has the anticancer effect on colon cancer cells via regulation of Bcl-2/Bax signal pathway.
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In this study, the antioxidative effects of a purified polysaccharide isolated from the stems of Acanthopanax koreanum Nakai (ASP) on hydrogen peroxide-induced oxidative stress was investigated both in vitro and in vivo using a zebrafish model. A. koreanum Nakai stem was hydrolyzed using five carbohydrases and five proteases for the enzyme-assistant extraction. Of the enzyme-assistant extracts, the Protamex extract exhibited the highest yield and a potent scavenging activity against free radicals. Ethanol-added separation and anion exchange chromatography were conducted to identify the active polysaccharide. The purified polysaccharide significantly scavenged hydrogen peroxide and reduced hydrogen peroxide-induced cell death in Vero cells and in zebrafish. The results reveal that ASP is a useful antioxidant polysaccharide and might be available for relevant industrial applications.
Asunto(s)
Antioxidantes/farmacología , Araliaceae/química , Tallos de la Planta/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Pez Cebra , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Muerte Celular/efectos de los fármacos , Células Cultivadas , Chlorocebus aethiops , Radicales Libres/antagonistas & inhibidores , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/farmacología , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Polisacáridos/química , Especies Reactivas de Oxígeno/metabolismo , Células VeroRESUMEN
We investigated the effect of Ecklonia cava (E. cava)-derived dieckol on movement behavior and the expression of migration-related genes in MCF-7 human breast cancer cell. Phlorotannins (e.g., dieckol, 6,6'-biecko, and 2,7â³-phloroglucinol-6,6'-bieckol) were purified from E. cava by using centrifugal partition chromatography. Among the phlorotannins, we found that dieckol inhibited breast cancer cell the most and was selected for further study. Radius™-well was used to assess cell migration, and dieckol (1-100 µM) was found to suppress breast cancer cell movement. Metastasis-related gene expressions were evaluated by RT-PCR and Western blot analysis. In addition, dieckol inhibited the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). On the other hand, it stimulated the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These results suggest that dieckol exerts anti-breast cancer activity via the regulation of the expressions of metastasis-related genes, and this is the first report on the anti-breast cancer effect of dieckol.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Benzofuranos/aislamiento & purificación , Neoplasias de la Mama/tratamiento farmacológico , Descubrimiento de Drogas , Phaeophyceae/química , Algas Marinas/química , Taninos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/farmacología , Benzofuranos/química , Benzofuranos/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Dioxanos/química , Dioxanos/aislamiento & purificación , Dioxanos/farmacología , Dioxinas/química , Dioxinas/aislamiento & purificación , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Metaloproteinasa 9 de la Matriz/química , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Océano Pacífico , Phaeophyceae/crecimiento & desarrollo , Floroglucinol/análogos & derivados , Floroglucinol/química , Floroglucinol/aislamiento & purificación , Floroglucinol/farmacología , República de Corea , Algas Marinas/crecimiento & desarrollo , Taninos/química , Taninos/farmacología , Inhibidor Tisular de Metaloproteinasa-1/agonistas , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/agonistas , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
In this study, we investigated the vasorelaxant and antihypertensive effects of gallic acid (GA), a polyphenol isolated from the green alga Spirogyra sp., to assess its suitability as a therapeutic for cardiovascular diseases (CVDs). We examined the effect of GA on endothelium-dependent vasorelaxation in human umbilical vein endothelial cells (HUVECs). GA increased nitric oxide (NO) levels by increasing phosphorylation of endothelial nitric oxide synthase (eNOS), and its effect on NO production was attenuated by pretreatment with the eNOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). We also investigated its antihypertensive effect by examining GA-mediated inhibition of angiotensin-I converting enzyme (ACE). GA inhibited ACE with a half-maximal inhibitory concentration (IC50) value of 37.38 ± 0.39 µg/ml. In silico simulations revealed that GA binds to the active site of ACE (PDB: 1O86) with a binding energy of -270.487 kcal/mol. Furthermore, GA clearly reduced blood pressure in spontaneously hypertensive rats (SHR) to an extent comparable to captopril. These results suggest that GA isolated from Spirogyra sp. exerts multiple therapeutic effects and has potential as a CVD treatment.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Antioxidantes/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Ácido Gálico/farmacología , Vasodilatadores/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Antihipertensivos/aislamiento & purificación , Antihipertensivos/uso terapéutico , Antioxidantes/aislamiento & purificación , Antioxidantes/uso terapéutico , Enfermedades Cardiovasculares/fisiopatología , Células Cultivadas , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3/metabolismo , Ácido Gálico/aislamiento & purificación , Ácido Gálico/uso terapéutico , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas , Ratas Endogámicas SHR , Spirogyra/química , Vasodilatadores/aislamiento & purificación , Vasodilatadores/uso terapéuticoRESUMEN
This study was designed to investigate whether phlorofucofuroeckol A inhibited α-glucosidase and α-amylase activities and alleviated postprandial hyperglycemia in diabetic mice. Phlorofucofuroeckol A that was isolated from Ecklonia cava (brown algae) demonstrated prominent inhibitory effects against α-glucosidase and α-amylase activities. The IC50 values of phlorofucofuroeckol A against α-glucosidase and α-amylase were 19.52 and 6.34µM, respectively. These inhibitory activities of phlorofucofuroeckol A were higher than those of acarbose, which was used as a positive control. Increases in postprandial blood glucose levels were significantly more suppressed in the group administered phlorofucofuroeckol A compared to the control group in both diabetic and normal mice. Moreover, the area under the curve was significantly lower after phlorofucofuroeckol A administration (2296 versus 2690mmolmin/l) in the diabetic mice. These results suggested that phlorofucofuroeckol A is a potent α-glucosidase inhibitor and can alleviate the postprandial hyperglycemia that is caused by starch.