RESUMEN
Hizikia fusiforme has a long history of consumption and medicinal use in China. It has been found that natural plants containing polyphenol-polysaccharide complexes have better activity compared with polyphenols and polysaccharides. Therefore, in this study on enzymatic hydrolysis and fractional alcohol precipitation, two kinds of polyphenol-polysaccharide complexes (PPC), PPC1 and PPC2, were initially obtained from Hizikia fusiforme, while the dephenolization of PPC1 and PPC2 produced PPC3 and PPC4. Through in vitro assays, PPC2 and PPC4 were found to have higher antioxidant activity, and thus were selected for testing the PPCs' anti-aging activity in a subsequent in vivo experiment with D-gal-induced aging in mice. The results indicated that PPCs could regulate the expressions of antioxidant enzymes and products of oxidation, elevate the expressions of genes and proteins related to the Nrf2 pathway in the mouse brain, enrich the gut microbiota species and increase the Bacteroidota-Firmicute (B/F) ratio. Above all, the Hizikia fusiforme polyphenol-polysaccharide complex has potential in the development of natural anti-aging drugs.
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Seaweed is an important food source, especially in many Asian countries, because of its high nutritional value; however, increasing arsenic (As) accumulation may pose serious hazards to human health. The influence of food components on As bioaccessibility and transformation in the high As-containing seaweed Hizikia fusiforme was determined using an in vitro gastrointestinal digestion method. The results showed that co-digestion with several daily foods (such as celery, broccoli, onion, green chili, tomato) produced a higher As bioaccessibility (approximately 6-11 % increase) compared with that of seaweed alone. Vegetables such as fennel (Foeniculum valgare Mill.), celery (Apium grareolens L.), blanched garlic leaves (Allium sativum L.), scallions (Allium fistulosum L.), ginger (Zingiber officinale Rosc.), and green pepper (Capsicum frutescens L. vat. grussum Bailey) decreased bioaccessible inorganic As (18-35 %) in both the gastric and small intestinal phases. Meanwhile, the process of reducing As(V) to As(III) also occurred during co-digestion with some food matrices. Egg white and other animal proteins were the most effective reducing agents, transforming >70 % As(V) into As(III) in the solution system. These results may have important implications for health risk assessment via co-consumption. The present study provides the first evidence showing that the co-consumption of some vegetables and proteins leads to a higher toxicity of inorganic arsenic-containing food. In addition, the positive and negative effects of co-digestion on the bioaccessibility of essential metals (iron, manganese) compared to single digestion were evaluated in this study.
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Arsénico , Capsicum , Algas Marinas , Animales , Humanos , Arsénico/metabolismo , Verduras/metabolismo , Algas Marinas/metabolismo , DigestiónRESUMEN
In this study, we extracted the polysaccharides from Hizikia fusiforme (HFPs) and evaluated their effects on the immune response of the mud crab Scylla paramamosain. Compositional analysis revealed that HFPs were composed mainly of mannuronic acid (49.05%) and fucose (22.29%) as sulfated polysaccharides, and the sugar chain structure was ß-type. These results indicated that HFPs have potential antioxidant and immunostimulation activity in vivo or in vitro assays. Through this research, we found that HFPs inhibited viral replication in white spot syndrome virus (WSSV)-infected crabs and promoted phagocytosis of Vibrio alginolyticus by hemocytes. Quantitative PCR results showed that HFPs up-regulated the expression levels of astakine, crustin, myosin, MCM7, STAT, TLR, JAK, CAP, and p53 in crab hemocytes. HFPs also promoted the activities of superoxide dismutase and acid phosphatase and the hemolymph antioxidant activities of crabs. HFPs maintained peroxidase activity after WSSV challenge, thereby providing protection against oxidative damage caused by the virus. HFPs also promoted apoptosis of hemocytes after WSSV infection. In addition, HFPs significantly enhanced the survival rate of WSSV-infected crabs. All results confirmed that HFPs improved the innate immunity of S. paramamosain by enhancing the expression of antimicrobial peptides, antioxidant enzyme activity, phagocytosis, and apoptosis. Therefore, HFPs have potential for use as therapeutic or preventive agents to regulate the innate immunity of mud crabs and protect them against microbial infection.
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Braquiuros , Virus del Síndrome de la Mancha Blanca 1 , Animales , Resistencia a la Enfermedad , Antioxidantes , Proteínas de Artrópodos , Inmunidad Innata/genética , Fagocitosis , Virus del Síndrome de la Mancha Blanca 1/fisiología , HemocitosRESUMEN
The study aims to identify the safety profile of a mixed extract (KGC-02-PS) from two traditional medicinal herbs, Puerariae radix and Hizikia fusiforme. In a subacute oral toxicity study, KGC-02-PS was administered orally for 28 days by gavage to Sprague Dawley rats (both sexes) at a daily dose of 0, 500, 1000, and 2000 mg/kg body weight. Bodyweight, food consumption, and clinical signs were monitored during the experimental period. After administering the final dose, this study conducted hematology, serum biochemistry, and pathological evaluations. In addition, the study performed a bacterial reverse mutation test with varying concentrations of KGC-02-PS (312.5 µg - 5,000 µg/plate) following OECD guideline No. 471, before testing five bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2) in the presence or absence of metabolic activation. The preclinical evaluation of KGC-02-PS's subacute oral toxicity yielded no associated toxicological effects or any changes in clinical signs, body weight, and food consumption. Moreover, examining KGC-02-PS's hematological and serum biochemical characteristics and pathology yielded no toxicological changes in terms of organ weight measurements and gross or histopathological findings. KGC-02-PS neither increased the number of revertant colonies in all bacterial strains used in the bacterial reverse mutation test, nor did it induce genotoxicity related to bacterial reverse mutations under the study's conditions. Also, KGC-02-PS's no-observed-adverse-effect level was greater than 2000 mg/kg.
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Mutágenos , Pueraria , Animales , Peso Corporal , Escherichia coli/genética , Femenino , Masculino , Pruebas de Mutagenicidad , Mutágenos/farmacología , Pueraria/genética , Ratas , Ratas Sprague-DawleyRESUMEN
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
In the current study, a functional polysaccharide fraction (HFP) was obtained from Hizikia fusiforme by ultrasound-assisted enzymatic extraction, and its structural characterization and hypoglycemic activity and potential molecular mechanism were investigated. The results indicated that HFP with high uronic acid was a heterogeneous polysaccharide composed of six monosaccharides. Congo red test explained that HFP had no triple helix conformation. AFM analysis revealed that HFP was spherical particle with flame-like aggregates and multiple strands closely arranged. Rheological analysis showed that HFP exhibited shear-thinning flow behavior. HFP significantly ameliorated diabetes-related symptoms and serum profiles and increased muscle glycogen storage in rats. HFP administration at 400â mg/kg body weight/day displayed greater advantages than metformin in controlling the levels of fasting blood glucose, triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA) of diabetic rats. Intervention of HFP up-regulated markedly the expression of AMPK-α, GLUT4, PI3K and Akt in skeletal muscle of diabetic rats at the mRNA and protein levels, revealing hypoglycemic effects of HFP may be related closely to improving insulin resistance and mitochondrial function of skeletal muscle.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Sargassum/química , Animales , Glucemia/efectos de los fármacos , Química Física , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Hipoglucemiantes/química , Resistencia a la Insulina , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Extractos Vegetales/química , Polisacáridos/química , Ratas , Ratas Sprague-DawleyRESUMEN
Various physiological benefits have been linked to Hizikia fusiforme (HF), an edible brown seaweed. Here, fucose-containing sulfated polysaccharides were extracted from celluclast-processed HF (SPHF) and their antitumor efficacy against bladder cancer was evaluated in vitro and in vivo. SPHF possesses high sulfated polysaccharide and fucose contents and free radical scavenging activities compared to those of celluclast-processed HF extracts (CHF). SPHF inhibited bladder cancer EJ cell proliferation via G1-phase cell cycle arrest. This was due to the induction of p21WAF1 expression associated with the downregulation of CDKs and cyclins. Moreover, JNK phosphorylation was identified as an SPHF-mediated signaling molecule. SPHF treatment also hindered the migration and invasion of EJ cells by inhibiting MMP-9 expression, which was attributed to the repression of transcriptional binding to NF-κB, AP-1, and Sp-1 in the MMP-9 promoter region. In an animal study, SPHF treatment suppressed EJ tumor growth in xenograft mice similarly to cisplatin. Furthermore, no toxicity signs were found after weight loss assessment, biochemical tests, and organ tissue immunostaining during oral administration of 20-200 mg/kg SPHF for 20 days. Therefore, our study demonstrates the antitumor efficacy of SPHF in vitro and in vivo, thus highlighting its potential for bladder cancer treatment development.
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Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Polisacáridos/administración & dosificación , Polisacáridos/farmacología , Algas Marinas/química , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Administración Oral , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Ciclinas/metabolismo , Modelos Animales de Enfermedad , Expresión Génica/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Polisacáridos/aislamiento & purificación , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
The previous study suggested that the sulfated polysaccharides from Hizikia fusiforme (HFPS) possess strong antioxidant activity. The purpose of this study is to isolate fucoidan from HFPS and to investigate its antioxidant activity. A fucoidan (HFPS-F4) with a molecular weight of 102.67 kDa was isolated from HFPS. HFPS-F4 contains 99.01% of fucoidan (71.79 ± 0.56% of carbohydrate and 27.22 ± 0.05% of sulfate content). The fucoidan increased the viability of H2O2-treated Vero cells by 5.41, 11.17, and 16.32% at the concentration of 12.5, 25, and 50 µg/mL, respectively. Further results demonstrated that this effect act diminishing apoptosis by scavenging intracellular reactive oxygen species (ROS) via increasing the expression of the endogenous antioxidant enzymes, which was induced by elevating total nuclear factor (erythroid-derived 2)-like 2 (Nrf2) levels. In addition, the in vivo test results displayed that the pretreatment of fucoidan improved the survival rates and decreased heart-beating rate, ROS, cell death, and lipid peroxidation in H2O2-stimulated zebrafish. Taken together, these results demonstrated that fucoidan isolated from HFPS has strong in vitro and in vivo antioxidant activities and it could be utilized in pharmaceutical, nutraceutical, and cosmeceutical industries.
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Cholinergic disorder, oxidative stress, and neuroinflammation play important roles in the pathology of Alzheimer's disease. To explore the healthy potential of the edible seaweed Hizikia fusiforme on this aspect, a functional oil (HFFO) was extracted from this alga and investigated on its constituents by gas chromatography-mass spectrometry (GC/MS) in this study. Its anti-Alzheimer's related bioactivities including acetylcholinesterase (AChE) inhibition, antioxidation, and anti-neuroinflammation were evaluated, traced, and simulated by inâ vitro and in silico methods. GC/MS analysis indicated that HFFO mainly contained arachidonic acid (ARA), 11,14,17-eicosatrienoic acid (ETrA), palmitic acid, phytol, etc. HFFO showed moderate AChE inhibition and antioxidant activity. Bioactivity tracing using commercial standards verified that AChE inhibition of HFFO mainly originated from ARA and ETrA, whereas antioxidant activity mainly from ARA. Lineweaver-Burk plots showed that both ARA and ETrA are noncompetitive AChE inhibitors. A molecular docking study demonstrated low CDOCKER interaction energy of -26.33â kcal/mol for ARA and -43.70â kcal/mol for ETrA when interacting with AChE and multiple interactions in the ARA (or ETrA)-AChE complex. In the anti-neuroinflammatory evaluation, HFFO showed no toxicity toward BV-2 cells at 20â µg/mL and effectively inhibited the production of nitroxide and reduced the level of reactive oxygen species in lipopolysaccharide-induced BV-2 cells. The results indicated that HFFO could be used in functional foods for its anti-Alzheimer's disease-related activities.
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Enfermedad de Alzheimer/tratamiento farmacológico , Aceites de Plantas/farmacología , Algas Marinas/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Cromatografía de Gases y Espectrometría de Masas , Humanos , Cinética , Simulación del Acoplamiento Molecular , Especies Reactivas de Oxígeno/metabolismoRESUMEN
We had observed in our previous study that the active fucoidan (JHCF4), isolated from the crude fucoidan in acid-processed Hizikia fusiforme, possessed an anticancer effect. In this study, the antioxidant effect of JHCF4 was evaluated. Among the fractions, JHCF4 showed the highest scavenging activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH), alkyl, and hydroxyl radicals, as well as protective effect against reactive oxygen species (ROS) in 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-treated Vero cells. Furthermore, JHCF4 showed a protective activity against AAPH-induced apoptosis, as observed by nuclear staining with Hoechst 33342. Our results showed that JHCF4 can up-regulate Bcl-xL, down-regulate Bax and cleave caspase-3 with increased concentrations in AAPH-induced Vero cells. JHCF4 induced anti-apoptosis via a mitochondria-mediated pathway. Additionally, JHCF4 was selected for further in vivo screening in a zebrafish model, which markedly decreased ROS generation and lipid peroxidation. Thus, JHCF4 showed a potential protective activity against AAPH-induced ROS both in vitro and in the zebrafish model.
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Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Polisacáridos/farmacología , Sargassum/química , Amidinas/química , Animales , Antioxidantes/farmacología , Compuestos de Bifenilo/química , Caspasa 3/metabolismo , Línea Celular , Chlorocebus aethiops , Regulación hacia Abajo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Picratos/química , Sustancias Protectoras/farmacología , Especies Reactivas de Oxígeno/metabolismo , Estilbestroles/química , Regulación hacia Arriba/efectos de los fármacos , Células Vero , Pez Cebra , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Previous studies have reported that Hizikia fusiforme, an edible brown seaweed, has diverse health-promoting effects; however, evidence for its anti-cancer potential is still lacking. In this study, we examined the effect of ethanol extract of H. fusiforme (EHF) on the proliferation of B16F10 mouse melanoma cells. METHODS: Analyses of cell viability and apoptosis were performed to study the actions of EHF on B16F10 cells. Cellular reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were measured using a flow cytometer. Western blot analysis was carried out to measure apoptosis and phosphoinositide 3-kinase (PI3K)/Akt signaling related proteins. RESULTS: EHF treatment significantly decreased B16F10 cell viability, which was associated with induction of apoptosis. EHF activated caspase-8 and caspase-9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and also increased caspase-3 activity, a typical effect caspase, subsequently leading to poly (ADP-ribose) polymerase cleavage. In addition, EHF destroyed the integrity of mitochondria and increased Bax/Bcl-2 ratio, which contributed to cytosolic release of cytochrome c. EHF further enhanced intracellular levels of ROS and the addition of N-acetyl cysteine (NAC), a ROS inhibitor, significantly diminished EHF-induced mitochondrial dysfunction and growth inhibition. Moreover, EHF inactivated the PI3K/Akt signaling pathway and LY294002, a PI3K/Akt inhibitor, increased the apoptosis-inducing effect of EHF. However, increased apoptosis and reduced cell viability by simultaneous treatment of EHF and LY294002 were significantly attenuated in the presence of NAC. CONCLUSION: These results indicate that EHF induces apoptosis through activation of extrinsic and intrinsic apoptotic pathways and ROS-dependent inactivation of PI3K/Akt signaling in B16F10 cells.
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Melanoma Experimental/tratamiento farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Phaeophyceae/química , Fosfatidilinositol 3-Quinasa/metabolismo , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis , Proliferación Celular , Etanol/química , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Células Tumorales CultivadasRESUMEN
The sea vegetable Hizikia fusiforme is not only a good source of dietary fiber but also enhances immunity. In this study, we investigated the effects of H. fusiforme on innate immunity in invertebrates, using white spot syndrome virus (WSSV) challenge in the crayfish, Procambarus clarkii. Supplementation with H. fusiforme significantly reduced mortality caused by WSSV infection and also reduced copy numbers of the WSSV protein VP28. Quantitative reverse transcription-polymerase chain reaction showed that supplementation of feed with H. fusiforme increased the expression of immune-related genes, including NF-κB and crustin 1. Further analysis showed that supplementation with H. fusiforme also affected three immune parameters, total hemocyte count, and phenoloxidase and superoxide dismutase activity. H. fusiforme treatment significantly increased hemocyte apoptosis rates in both WSSV-infected and uninfected crayfish. H. fusiforme thus regulates the innate immunity of crayfish, and both delays and reduces mortality after WSSV challenge. Our study demonstrates the potential for the commercial use of H. fusiforme, either therapeutically or prophylactically, to regulate the innate immunity and protect crayfish against WSSV infection.
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Astacoidea/inmunología , Inmunidad Innata/efectos de los fármacos , Sargassum/química , Proteínas del Envoltorio Viral/genética , Virus del Síndrome de la Mancha Blanca 1/fisiología , Alimentación Animal/análisis , Animales , Apoptosis/efectos de los fármacos , Astacoidea/efectos de los fármacos , Astacoidea/virología , Variaciones en el Número de Copia de ADN/efectos de los fármacos , Dieta , Suplementos Dietéticos/análisis , Longevidad/efectos de los fármacos , Distribución Aleatoria , Replicación Viral/efectos de los fármacosRESUMEN
Objective: To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells.Methods: Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Apoptosis and mitochondrial membrane potential (MMP) were measured using flow cytometry in PC3 cells. DNA damage was assessed by nuclear staining and DNA fragmentation assay. Expressions of apoptosis-associated proteins were determined by Western blotting assays. Activities of caspase-3, -8, and -9 were determined by colorimetric assay. Moreover, intracellular reactive oxygen species (ROS) generation was detected using a flow cytometer and fluorescence microscope. Results: Treatment of PC3 cells with ethanol extracts of Hizikia fusiforme inhibited proliferation, which was associated with induction of apoptosis, and accompanied by increased expression of Fas, Fas-ligand (FasL), Bax and tBid, and decreased expression of Bcl-2. In addition, ethanol extracts of Hizikia fusiforme reduced c-Flip expression and activated caspase-8, -9 and -3, resulting in an increase in poly (ADP-ribose) polymerase (PARP)cleavage. However, in the presence of a pan-caspase inhibitor, ethanol extracts of Hizikia fusiforme-mediated growth inhibition and apoptosis were significantly attenuated. Ethanol extracts of Hizikia fusiforme also destroyed the integrity of mitochondria due to the loss of MMP, leading to cytosolic release of cytochrome c. Moreover, the levels of ROS were markedly increased by treatment with ethanol extracts of Hizikia fusiforme, which was significantly suppressed by the ROS scavenger N-acetyl-L-cysteine. Further investigation of whether ethanol extracts of Hizikia fusiforme-induced apoptosis was related to the generation of ROS was conducted and the results showed that N-acetyl-L-cysteine fully blocked ethanol extracts of Hizikia fusiforme-induced apoptotic events including loss of MMP, activation of caspase-3, the cytosolic release of cytochrome c and cytotoxicity.Conclusions: Ethanol extracts of Hizikia fusiforme have chemopreventive potential via induction of ROS-dependent apoptosis. Therefore, ethanol extracts of Hizikia fusiforme may be useful for developing effective and selective natural sources to inhibit cancer cell proliferation.
RESUMEN
Objective: To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells. Methods: Cell viability was evaluated using 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide. Apoptosis and mitochondrial membrane potential (MMP) were measured using flow cytometry in PC3 cells. DNA damage was assessed by nuclear staining and DNA fragmentation assay. Expressions of apoptosis-associated proteins were determined by Western blotting assays. Activities of caspase-3, -8, and -9 were determined by colorimetric assay. Moreover, intracellular reactive oxygen species (ROS) generation was detected using a flow cytometer and fluorescence microscope. Results: Treatment of PC3 cells with ethanol extracts of Hizikia fusiforme inhibited proliferation, which was associated with induction of apoptosis, and accompanied by increased expression of Fas, Fas-ligand (FasL), Bax and tBid, and decreased expression of Bcl-2. In addition, ethanol extracts of Hizikia fusiforme reduced c-Flip expression and activated caspase-8, -9 and -3, resulting in an increase in poly (ADP-ribose) polymerase (PARP)cleavage. However, in the presence of a pan-caspase inhibitor, ethanol extracts of Hizikia fusiforme-mediated growth inhibition and apoptosis were significantly attenuated. Ethanol extracts of Hizikia fusiforme also destroyed the integrity of mitochondria due to the loss of MMP, leading to cytosolic release of cytochrome c. Moreover, the levels of ROS were markedly increased by treatment with ethanol extracts of Hizikia fusiforme, which was significantly suppressed by the ROS scavenger N-acetyl-L-cysteine. Further investigation of whether ethanol extracts of Hizikia fusiforme-induced apoptosis was related to the generation of ROS was conducted and the results showed that N-acetyl-L-cysteine fully blocked ethanol extracts of Hizikia fusiforme-induced apoptotic events including loss of MMP, activation of caspase-3, the cytosolic release of cytochrome c and cytotoxicity. Conclusions: Ethanol extracts of Hizikia fusiforme have chemopreventive potential via induction of ROS-dependent apoptosis. Therefore, ethanol extracts of Hizikia fusiforme may be useful for developing effective and selective natural sources to inhibit cancer cell proliferation.
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The aim of this study was to investigate the antiproliferative effects of fucoidan from three regional hijiki (Hizikia fusiforme) samples (Zhejiang-China, Jeju-Korea [JH], and Wando-Korea) in East Asia. Hijiki was processed using 1% citric acid to decrease heavy metal content. The JH sample was separated using diethylaminoethyl-cellulose-ion exchange chromatography to obtain four active fractions (JHCF1-JHCF4) and their monosaccharide composition was detected using high-performance liquid chromatography. The structure of the crude polysaccharides and four fucoidan fractions was analyzed using Fourier-transform infrared spectroscopy. JHCF4 showed the highest fucose and sulfate content and decreased Hep3B cell growth in 48â¯h with a half-maximal inhibitory concentration of 33.53⯱â¯2.50⯵g/ml, which represented the strongest anticancer activity. Further, nuclear staining with Hoechst 33342 and acridine orange-ethidium bromide staining demonstrated that the anticancer activity of JHCF4 was mediated by apoptosis. Moreover, JHCF4 down-regulated B-cell lymphoma extra-large, while up-regulating Bcl-2-associated X protein, caspase-3, and apoptotic bodies to different degrees in Hep3B cells. JHCF4 induced apoptosis via the generation of reactive oxygen species along with the concurrent loss of mitochondrial membrane potential, indicating the potential role of the mitochondria-mediated pathway. Therefore, these results indicate that JHCF4 exhibited antiproliferative effects on the investigated cancer cell lines.
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Antineoplásicos/química , Antineoplásicos/farmacología , Manipulación de Alimentos , Polisacáridos/química , Polisacáridos/farmacología , Sargassum/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Humanos , Concentración de Iones de Hidrógeno , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
Our previous study evaluated the antioxidant activities of sulfated polysaccharides from Celluclast-assisted extract of Hizikia fusiforme (HFPS) in vitro in Vero cells and in vivo in zebrafish. The results showed that HFPS possesses strong antioxidant activity and suggested the potential photo-protective activities of HFPS. Hence, in the present study, we investigated the protective effects of HFPS against ultraviolet (UV) B-induced skin damage in vitro in human dermal fibroblasts (HDF cells). The results indicate that HFPS significantly reduced intracellular reactive oxygen species (ROS) level and improved the viability of UVB-irradiated HDF cells in a dose-dependent manner. Furthermore, HFPS significantly inhibited intracellular collagenase and elastase activities, remarkably protected collagen synthesis, and reduced matrix metalloproteinases (MMPs) expression by regulating nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinases (MAPKs) signaling pathways in UVB-irradiated HDF cells. These results suggest that HFPS possesses strong UV protective effect, and can be a potential ingredient in the pharmaceutical and cosmetic industries.
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Fibroblastos/efectos de los fármacos , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Sustancias Protectoras/farmacología , Sargassum/química , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Línea Celular , Colagenasas/metabolismo , Fibroblastos/metabolismo , Humanos , Metaloproteinasas de la Matriz/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Elastasa Pancreática/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Piel/metabolismo , Factor de Transcripción AP-1/metabolismo , Rayos Ultravioleta/efectos adversosRESUMEN
Laminaria japonica (LJ) and Hizikia fusiforme (HF) are brown seaweeds known to have various health-promoting effects. In this study, we investigated the anti-diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro and in vivo models. C2C12 myotubes, mouse-derived skeletal muscle cells, treated with LF or HF extracts were used for the in vitro model, and muscle tissues from C57BL/6N mice fed a high-fat diet supplemented with 5% LF or HF for 16 weeks were used for the in vivo model. Although both the LF and HF extracts significantly inhibited α-glucosidase activity in a dose-dependent manner, the HF extract had a superior α-glucosidase inhibition than the LF extract. In addition, glucose uptake was significantly increased by LJ- and HF-treated groups when compared to the control group. Phosphorylation of protein kinase B and AMP-activated protein kinase was induced by LJ and HF in both the vivo and in vitro skeletal muscle models. Furthermore, LJ and HF significantly decreased tumor necrosis factor-α whereas both extracts increased interleukin (IL)-6 and IL-10 production in lipopolysaccharide-stimulated C2C12 myotubes. Taken together, these findings imply that the brown seaweeds LJ and HF could be useful therapeutic agents to attenuate muscle insulin resistance due to diet-induced obesity and its associated inflammation.
Asunto(s)
Inflamación/tratamiento farmacológico , Músculo Esquelético/efectos de los fármacos , Phaeophyceae/química , Extractos Vegetales/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus , Dieta Alta en Grasa , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Inhibidores de Glicósido Hidrolasas , Inflamación/inducido químicamente , Laminaria/química , Masculino , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/química , alfa-Glucosidasas/metabolismoRESUMEN
The purpose of this study was to evaluate the effects of hiziki extract on alveolar bone loss, inflammation, and osteo-biomarker expression in hPDL cells (10, 50, 100 µg/ml final concentrations in culture medium) and on a ligature-induced periodontitis rat model (50, 100, 200 mg/kg with oral administration). Hiziki extract increased alkaline phosphatase activity and mineralized nodule formation in hPDL cell. In western blot analysis, hiziki extract resulted in increased expression of osteoblast markers, including transforming growth factor beta (TGF-ß), SMAD anchor for receptor activation (SARA) and runt-related transcription factor 2 (RUNX2) in hDPL cells. Additionally, expression of osteoclast markers and inflammatory cytokines was inhibited, which were receptor activator of NF-κB (RANK), RANK receptor (RANKL) and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). Hiziki extract also prevented alveolar bone loss in a ligature-induced periodontitis rat model through reducing the distance between cementoenamel junction and alveolar bone crest (CBJ-ABC) and furcation involvement. These findings suggested that hiziki extract has prophylactic potential for the prevention of periodontitis through anti-inflammation and, anti-bone resorption effects and the inhibition of alveolar bone destruction.
Asunto(s)
Pérdida de Hueso Alveolar/metabolismo , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Extractos Vegetales/uso terapéutico , Fosfatasa Alcalina/metabolismo , Animales , Western Blotting , Calcificación Fisiológica/efectos de los fármacos , Calcificación Fisiológica/fisiología , Células Cultivadas , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Ligando RANK/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Capsosiphon fulvescens (green seaweed) and Hizikia fusiforme (brown seaweed) are marine algae consumed as food supplements, especially in Japan, China and Korea, and are considered traditional medicinal tonics for certain ailments. The aim of this study was to investigate the possible inhibitory effects of dietary C. fulvescens and H. fusiforme on azoxymethane (AOM)-induced colorectal cancer (CRC) in rats. F344 male rats (5 weeks, 150 g) were divided into six groups as follows. Group 1: Injected with normal saline solution and fed control diet (untreated control). Group 2: Injected with AOM and fed control diet (treated control). Group 3: Injected with AOM and fed 1% C. fulvescens diet. Group 4: Injected with AOM and fed 2% C. fulvescens diet. Group 5: Injected with AOM and fed 2% H. fusiforme diet. Group 6: Injected with AOM and fed 6% H. fusiforme diet. Test animals received subcutaneous injections of AOM (15 mg/1 ml/kg body weight) once a week for 2 weeks to induce aberrant crypt foci (ACF) in treated control and experimental groups. We evaluated the effects of dietary C. fulvescens and H. fusiforme at two different dose levels: 1 and 2% C. fulvescens, and 2 and 6% H. fusiforme, on colonic carcinogenesis by AOM in rats. Our results suggest that body weights were not significantly different amongst groups. We found that feeding C. fulvescens and H. fusiforme with a control diet significantly (p<0.05) inhibited the development of ACF in experimental groups. C. fulvescens and H. fusiforme in food also significantly (p<0.05) reduced the proliferating cell nuclear antigen labeling index in the colonic tissues of experimental groups. These results demonstrate the chemopreventive potential of C. fulvescens and H. fusiforme against CRC in an AOM-induced rats.
Asunto(s)
Focos de Criptas Aberrantes/prevención & control , Productos Biológicos/farmacología , Chlorophyta/química , Neoplasias del Colon/prevención & control , Phaeophyceae/química , Focos de Criptas Aberrantes/inducido químicamente , Animales , Azoximetano , Productos Biológicos/administración & dosificación , Colon/efectos de los fármacos , Colon/patología , Neoplasias del Colon/inducido químicamente , Suplementos Dietéticos , Masculino , Ratas Endogámicas F344RESUMEN
Hizikia fusiforme, a brown seaweed, has been utilized as a health food and in traditional medicine. In this study, we investigated whether enzyme-modified H. fusiforme extracts (EH) have immunological effects compared with normal H. fusiforme extracts (NH). The effects of NH and EH on immune responses were investigated by assessing nitric oxide (NO) production, phagocytosis, and cytokine secretion in RAW 264.7 murine macrophages and mice. Also, fucosterol was evaluated to find the active component of NH and EH by addressing cytotoxicity test and NO production. Both of NH and EH significantly increased cell viability and NO synthesis. Tumor necrosis factor-α (TNF-α) expression was more induced by EH with LPS treatment. Phagocytic activity, as the primary function of macrophages, was markedly induced by EH treatment. Additionally, EH encouraged splenocyte proliferation and recovered the levels of cytokines IL-1ß, IL-6, and TNF-α in mice. Finally, fucosterol increased NO production with no cytotoxicity, which means that fucosterol is an active component of EH. In conclusion, EH has the potential to modulate immune function and could offer positive therapeutic effect for immune system diseases.