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1.
Mar Drugs ; 22(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38535450

RESUMO

A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from Padina arborescens (PAC) using celluclast-assisted extraction, purified, and evaluated for its anti-inflammatory potential in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structural analyses were performed using Fourier transform infrared (FTIR) and scanning electron microscopy. Among the purified fucoidans, fucoidan fraction 5 (F5) exhibited strong inhibitory activity against LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine generation through the regulation of iNOS/COX-2, MAPK, and NF-κB signaling in LPS-induced RAW 264.7 cells. Determination of the structural characteristics indicated that purified F5 exhibited characteristics similar to those of commercial fucoidan. In addition, further analyses suggested that F5 inhibits LPS-induced toxicity, cell death, and NO generation in zebrafish models. Taken together, these findings imply that P. arborescens fucoidans have exceptional anti-inflammatory action, both in vitro and in vivo, and that they may have prospective uses in the functional food sector.


Assuntos
Lipopolissacarídeos , Phaeophyceae , Animais , Peixe-Zebra , Polissacarídeos , Inflamação , Óxido Nítrico
2.
Int Immunopharmacol ; 131: 111851, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38492337

RESUMO

Allergic diseases have become a serious problem worldwide and occur when the immune system overreacts to stimuli. Sargassum horneri is an edible marine brown alga with pharmacological relevance in treating various allergy-related conditions. Therefore, this study aimed to investigate the effect of fucosterol (FST) isolated from S. horneri on immunoglobulin E(IgE)/bovine serum albumin (BSA)-stimulated allergic reactions in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice. The in silico analysis results revealed the binding site modulatory potential of FST on the IgE and IgE-FcεRI complex. The findings of the study revealed that FST significantly suppressed the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of ß-hexosaminidase and histamine in a dose-dependent manner. In addition, FST effectively decreased the expression of FcεRI on the surface of BMCMCs and its IgE binding. FST dose-dependently downregulated the expression of allergy-related cytokines (interleukin (IL)-4, -5, -6, -13, tumor necrosis factor (TNF)-α, and a chemokine (thymus and activation-regulated chemokine (TARC)) by suppressing the activation of nuclear factor-κB (NF-κB) and Syk-LAT-ERK-Gab2 signaling in IgE/BSA-stimulated BMCMCs. As per the histological analysis results of the in vivo studies with IgE-mediated PCA in BALB/c mice, FST treatment effectively attenuated the PCA reactions. These findings suggest that FST has an immunopharmacological potential as a naturally available bioactive compound for treating allergic reactions.


Assuntos
Anafilaxia , Antialérgicos , Hipersensibilidade , Sargassum , Estigmasterol/análogos & derivados , Camundongos , Animais , Imunoglobulina E/metabolismo , Soroalbumina Bovina , Sargassum/metabolismo , Mastócitos , Anafilaxia Cutânea Passiva , Hipersensibilidade/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Degranulação Celular , Camundongos Endogâmicos BALB C , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico
3.
Int J Biol Macromol ; 253(Pt 5): 127212, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37802428

RESUMO

Fucoidan has been reported to have various biological activities, such as antioxidant, antitumor and anticoagulant, with various health benefits. However, few studies have been conducted to extract fucoidan from Sargassum thunbergii in terms of its immuno-enhancing activities. This aim of this study was to investigate the immuno-enhancing effect of fucoidan (S3) isolated from Sargassum thunbergii through water extraction and ethanol precipitation in RAW 264.7 macrophages and zebrafish. The results showed that S3 contained a relatively high content of fucose and sulfated polysaccharide. Fourier-transform infrared spectroscopy (FTIR) results show that the characteristic peaks at 845 cm-1 and 1220-1270 cm-1 indicate that S3 contains sulfate groups. In vitro, S3 effectively enhanced nitric oxide (NO) production and phagocytic activity. In addition, the results of the study demonstrated that the secretion of tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, and IL-10 was upregulated by nuclear factor kappa B (NF-κB) signaling pathway in a dose-dependent manner. In vivo, S3 activates zebrafish immune responses by promoting secretion of NO and activating the NF-κB pathway. Overall, these results suggest that S3 could be used as a functional ingredient added to nutritional supplements and functional foods.


Assuntos
Sargassum , Alga Marinha , Animais , Sargassum/química , Alga Marinha/metabolismo , Peixe-Zebra/metabolismo , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química
4.
Polymers (Basel) ; 15(8)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37112059

RESUMO

Our previous studies have evaluated the bioactivities of a fucoidan isolated from Sargassum fusiforme (SF-F). To further investigate the health benefit of SF-F, in the present study, the protective effect of SF-F against ethanol (EtOH)-induced oxidative damage has been evaluated in in vitro and in vivo models. SF-F effectively improved the viability of EtOH-treated Chang liver cells by suppressing apoptosis. In addition, the in vivo test results indicate that SF-F significantly and dose-dependently increased the survival rate of zebrafish treated with EtOH. Further research results show that this action works through decreasing cell death via reduced lipid peroxidation by scavenging intracellular reactive oxygen species in EtOH-stimulated zebrafish. These results indicate that SF-F effectively protected Chang liver cells and zebrafish against EtOH-induced oxidative damage and suggest the potential of SF-F to be used as an ingredient in the functional food industry.

5.
Mar Drugs ; 20(5)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35621931

RESUMO

The in vitro capacity of Ishige okamurae extract (IO) to improve impaired muscle function has been previously examined. However, the mechanism underlying IO-mediated muscle protein metabolism and the role of its component, Ishophloroglucin A (IPA), in mice with dexamethasone (Dexa)-induced muscle atrophy remains unknown. In the present study, we evaluated the effect of IO and IPA supplementation on Dexa-induced muscle atrophy by assessing muscle protein metabolism in gastrocnemius and soleus muscles of mice. IO and IPA supplementation improved the Dexa-induced decrease in muscle weight and width, leading to enhanced grip strength. In addition, IO and IPA supplementation regulated impaired protein synthesis (PI3K and Akt) or degradation (muscle-specific ubiquitin ligase muscle RING finger and atrogin-1) by modulating mRNA levels in gastrocnemius and soleus muscles. Additionally, IO and IPA upregulated mRNA levels associated with muscle growth activation (transient receptor potential vanilloid type 4 and adenosine A1 receptor) or inhibition (myostatin and sirtuin 1) in gastrocnemius and soleus muscle tissues of Dexa-induced mice. Collectively, these results suggest that IO and IO-derived IPA can regulate muscle growth through muscle protein metabolism in Dexa-induced muscle atrophy.


Assuntos
Misturas Complexas , Proteínas Musculares , Atrofia Muscular , Phaeophyceae , Animais , Benzofuranos , Misturas Complexas/farmacologia , Misturas Complexas/uso terapêutico , Dexametasona/efeitos adversos , Dioxinas , Camundongos , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Phaeophyceae/metabolismo , RNA Mensageiro/metabolismo
6.
Pharmaceutics ; 14(4)2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35456553

RESUMO

Muscle atrophy refers to the loss of skeletal muscle mass, myofiber size, and related physical functions such as walking speed or grip strength caused by aging or a lack of physical activity due to injury or illness and can also be attributed to excessive exposure to corticosteroids. Ishige okamurae (IO) and its active component, diphlorethohydroxycarmalol (DPHC), have been known to improve glucose homeostasis by controlling the contraction of skeletal muscles. Based on this idea, we hypothesized that the effects of DPHC and IO extract on muscle metabolism are associated with their role in improving muscle physical function. This study assessed the effects of DPHC or IO extract on muscle behavioral responses with their metabolic properties in muscle atrophy induced by glucocorticoids and dexamethasone (DEX) in vivo. In addition to the improvement in muscle behavioral response by DPHC or IO extract, the loss of muscle fiber and the related metabolic properties by DEX exposure in the gastrocnemius and soleus of calf muscle was prevented. These findings suggest that IO extract and its active component DPHC can potentially prevent muscle atrophy caused by exposure to corticosteroids and could be used to treat reverse skeletal atrophy.

7.
Foods ; 11(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35159514

RESUMO

Turbo cornutus, the horned turban sea snail, is found along the intertidal and basaltic shorelines and is an important fishery resource of Jeju Island. In this study, we performed a preliminary study on anti-inflammatory effect of 70% ethanol extract obtained from T. cornutus viscera (TVE) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro and zebrafish embryos in vivo. TVE reduced the production of LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) without any toxic effects. TVE also decreased the protein expression of LPS-induced inducible NO synthase and cyclooxygenase-2 and suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß. Furthermore, mechanistic studies indicated that TVE suppressed c-Jun N-terminal kinase phosphorylation and nuclear factor-kB activation. In zebrafish embryos, TVE did not show developmental toxicity based on the survival rate and cell death findings. In LPS-stimulated zebrafish embryos, TVE suppressed NO production and cell death. In conclusion, the result from this preliminary study showed TVE has a potential anti-inflammatory property that can be exploited as a functional food ingredient.

8.
Chemosphere ; 293: 133602, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35032516

RESUMO

Pollution caused by fine dust is becoming a global problem in the aquatic environment. Many studies have investigated the hazards that fine dust may pose to terrestrial organisms; however, information on the effects on aquatic environments remain limited. In this study, the physicochemical characteristics of the fine dust associated with the captured powder or liquid state were compared using scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). Raw fine dust (RFD), in the captured powder state, was suspended in water (SFD), and the elemental composition, morphology, and size distribution of both were analyzed. Zebrafish were used as a model to study the effects of SFD-exposure on aquatic organisms. A fatal malformation was observed in the integuments of zebrafish exposed to SFD, specifically in the exterior and interior eye tissues. Furthermore, the exposure of SFD to Tg (flk; EGFP) zebrafish remarkably increased ocular vessel diameter expansion along with blood flow velocity. Regarding vessel diameter expansion, EA.hy926 cells exposed to SFD were adversely affected, with a significant increase in cell migration and capillary-like structure formation, which are angiogenic markers. The SFD-induced angiogenesis in vitro and in vivo was dramatically restored to normal via α/ß-adenosine isolated from the anti-angiogenic brown algae Ishige okamurae extract. Taken together, the current study presents solid evidence of the altered physicochemical characteristics of SFD compared to RFD, and the detrimental impact of SFD in an aquatic in vivo zebrafish model. In addition, the protective effect of α/ß-adenosine, a marine natural product, on SFD-induced angiogenesis suggests that it can be used as an agent to reduce the adverse effects of SFD on aquatic animals.


Assuntos
Poeira , Phaeophyceae , Animais , Poeira/análise , Phaeophyceae/química , Pós , Substâncias Protetoras , Peixe-Zebra
9.
Mar Drugs ; 19(12)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34940677

RESUMO

Fucoidans are sulfated heteropolysaccharides found in the cell walls of brown seaweeds (Phaeophyceae) and in some marine invertebrates. Generally, fucoidans are composed of significant amounts of L-fucose and sulfate groups, and lesser amounts of arabinose, galactose, glucose, glucuronic acid, mannose, rhamnose, and xylose. In recent years, fucoidans isolated from brown seaweeds have gained considerable attention owing to their promising bioactive properties such as antioxidant, immunomodulatory, anti-inflammatory, antiobesity, antidiabetic, and anticancer properties. Inflammation is a complex immune response that protects the organs from infection and tissue injury. While controlled inflammatory responses are beneficial to the host, leading to the removal of immunostimulants from the host tissues and restoration of structural and physiological functions in the host tissues, chronic inflammatory responses are often associated with the pathogenesis of tumor development, arthritis, cardiovascular diseases, diabetes, obesity, and neurodegenerative diseases. In this review, the authors mainly discuss the studies since 2016 that have reported anti-inflammatory properties of fucoidans isolated from various brown seaweeds, and their potential as a novel functional material for the treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Polissacarídeos/farmacologia , Alga Marinha , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Organismos Aquáticos , Doenças Cardiovasculares/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/uso terapêutico
10.
Cells ; 10(11)2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34831102

RESUMO

Loss of myofibers during muscle atrophy affects functional capacity and quality of life. Dexamethasone, an inducer of rapid atrophy of skeletal myofibers, has been studied as a glucocorticoid receptor in muscle atrophy or motor neurodegeneration. In this study, we examined dexamethasone-induced muscle atrophy using zebrafish (Danio rerio), a vertebrate model, and assessed whether administration of Lepidium meyenii (maca) as a dietary supplement can prevent muscle atrophy. Changes in skeletal myofibers in zebrafish were evaluated after exposure to dexamethasone for different periods and at different concentrations. Under optimized conditions, zebrafish pre-fed with maca for 3 days were exposed to 0.01% dexamethasone for 1 h/day for 7 days. Thereafter, myofiber loss, damaged muscle contractile proteins, and abnormal exploratory behavior due to the structural and functional impairment of skeletal muscle associated with muscle atrophy were investigated using hematoxylin-eosin, immunofluorescence staining, and behavioral analyses. Our findings suggest that dexamethasone induces muscle atrophy in zebrafish, inhibiting exploratory behavior by inducing myofiber loss, inhibiting muscle contraction, and causing changes in endurance and velocity. Thus, the zebrafish model can be used to screen pharmaceutical agents and to study muscle atrophy. Furthermore, maca is a potential dietary supplement to prevent muscle atrophy, as it protects muscle fibers.


Assuntos
Dexametasona/efeitos adversos , Lepidium/química , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/prevenção & controle , Extratos Vegetais/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Extratos Vegetais/farmacologia , Natação/fisiologia , Peixe-Zebra
11.
Mar Drugs ; 19(5)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063550

RESUMO

In the present study, the in vitro and in vivo anti-inflammatory effects of the sulfated polysaccharides isolated from Sargassum fulvellum (SFPS) were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that SFPS improved the viability of LPS-stimulated RAW 264.7 macrophages from 80.02 to 86.80, 90.09, and 94.62% at the concentration of 25, 50, and 100 µg/mL, respectively. Also, SFPS remarkably and concentration-dependently decreased the production levels of inflammatory molecules including nitric oxide (NO), tumor necrosis factor-alpha, prostaglandin E2, interleukin-1 beta, and interleukin-6 in LPS-treated RAW 264.7 macrophages. In addition, SFPS significantly inhibited the expression levels of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-treated RAW 264.7 macrophages. Furthermore, the in vivo test results indicated that SFPS improved the survival rate of LPS-treated zebrafish from 53.33 to 56.67, 60.00, and 70.00% at the concentration of 25, 50, and 100 µg/mL, respectively. In addition, SFPS effectively reduced cell death, reactive oxygen species, and NO levels in LPS-stimulated zebrafish. Taken together, these results suggested that SFPS possesses strong in vitro and in vivo anti-inflammatory activities, and could be used as an ingredient to develop anti-inflammatory agents in the functional food and pharmaceutical industries.


Assuntos
Anti-Inflamatórios/farmacologia , Polissacarídeos/farmacologia , Sargassum/química , Alga Marinha/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Morte Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Sulfatos/química , Taxa de Sobrevida , Peixe-Zebra
12.
Biomed Pharmacother ; 138: 111431, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33752058

RESUMO

Abnormalities in angiogenesis that are associated with diabetes may contribute to vascular complications and result in disabilities and death. Furthermore, an imbalance in angiogenesis in different tissues, including the retina and kidney, can play a role in the pathogenesis of diabetic microvascular complications. Phlorotannins, such as phloroglucinol (PG) and dieckol (DK), which are found in Ecklonia cava exhibit antioxidant and anti-inflammatory activities that improve endothelial function in hypertension. However, reports on the effects of these compounds on diabetes-induced angiogenesis in vivo and in vitro are scarce. In this study, we assessed the antiangiogenic effects of PG and DK on endothelial cells treated with a high concentration of glucose to mimic angiogenesis. In addition, we sought to determine the effects of these compounds on cell proliferation, cell migration, and capillary formation. In silico docking of PG and DK into VEGFR-2 revealed their potential as therapeutic agents against angiogenesis. Further, both compounds were identified to inhibit the formation of the retinal vessel in transgenic zebrafish (flk:EGFP) embryos under high glucose conditions. These findings suggested that PG and DK derived from E. cava are potential inhibitors of angiogenesis in diabetic vascular complications and could, therefore, be used to develop angiogenic agents.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Benzofuranos/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Phaeophyceae , Floroglucinol/uso terapêutico , Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Animais , Animais Geneticamente Modificados , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Glucose/toxicidade , Humanos , Floroglucinol/isolamento & purificação , Floroglucinol/farmacologia , Estrutura Terciária de Proteína , Peixe-Zebra
13.
Antioxidants (Basel) ; 10(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652913

RESUMO

Ultraviolet (UV) irradiation is considered to be the primary environmental factor that causes skin damage. In the present study, we investigated the protective effect of dieckol (DK), a compound isolated from the brown seaweed Ecklonia cava, against UVB-induced skin damage in human dermal fibroblasts (HDF cells). The results indicated that DK effectively inhibited the activity of collagenase. DK remarkably reduced the intracellular reactive oxygen species level and improved the viability of UVB-irradiated HDF cells. Besides, DK significantly and dose-dependently improved collagen synthesis and inhibited intracellular collagenase activity in UVB-irradiated HDF cells. In addition, DK markedly reduced the expression of proinflammatory cytokines and matrix metalloproteinases. Further analyses revealed that these processes were mediated through the regulation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinase signaling pathways in the UVB-irradiated HDF cells. In conclusion, these results indicate that DK possesses strong in vitro photoprotective effects and therefore has the potential to be used as an ingredient in the cosmeceutical industry.

14.
Oxid Med Cell Longev ; 2021: 8893679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628395

RESUMO

Diphlorethohydroxycarmalol (DPHC), a type of phlorotannin isolated from the marine alga Ishige okamurae, reportedly alleviates impaired glucose tolerance. However, the molecular mechanisms of DPHC regulatory activity and by which it exerts potential beneficial effects on glucose transport into skeletal myotubes to control glucose homeostasis remain largely unexplored. The aim of this study was to evaluate the effect of DPHC on cytosolic Ca2+ levels and its correlation with blood glucose transport in skeletal myotubes in vitro and in vivo. Cytosolic Ca2+ levels upon DPHC treatment were evaluated in skeletal myotubes and zebrafish larvae by Ca2+ imaging using Fluo-4. We investigated the effect of DPHC on the blood glucose level and glucose transport pathway in a hyperglycemic zebrafish. DPHC was shown to control blood glucose levels by accelerating glucose transport; this effect was associated with elevated cytosolic Ca2+ levels in skeletal myotubes. Moreover, the increased cytosolic Ca2+ level caused by DPHC can facilitate the Glut4/AMPK pathways of the skeletal muscle in activating glucose metabolism, thereby regulating muscle contraction through the regulation of expression of troponin I/C, CaMKII, and ATP. Our findings provide insights into the mechanism of DPHC activity in skeletal myotubes, suggesting that increased cytosolic Ca2+ levels caused by DPHC can promote glucose transport into skeletal myotubes to modulate blood glucose levels, thus indicating the potential use of DPHC in the prevention of diabetes.


Assuntos
Cálcio/metabolismo , Glucose/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Músculo Esquelético/metabolismo , Phaeophyceae/química , Animais , Transporte Biológico/efeitos dos fármacos , Glicemia/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citosol/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Compostos Heterocíclicos com 3 Anéis/toxicidade , Larva/efeitos dos fármacos , Larva/metabolismo , Contração Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
15.
Int J Mol Sci ; 22(4)2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33562632

RESUMO

Nitric oxide (NO) is released by endothelial cells in the blood vessel wall to enhance vasodilation. Marine polyphenols are known to have protective effects against vascular dysfunction and hypertension. The present study is the first to investigate how diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae affects calcium levels, resulting in enhanced vasodilation. We examined calcium modulation with the well-known receptors, acetylcholine receptor (AchR) and vascular endothelial growth factor 2 (VEGFR2), which are related to NO formation, and further confirmed the vasodilatory effect of DPHC. We confirmed that DPHC stimulated NO production by increasing calcium levels and endothelial nitric oxide synthase (eNOS) expression. DPHC affected AchR and VEGFR2 expression, thereby influencing transient calcium intake. Specific antagonists, atropine and SU5416, were used to verify our findings. Furthermore, based on the results of in vivo experiments, we treated Tg(flk:EGFP) transgenic zebrafish with DPHC to confirm its vasodilatory effect. In conclusion, the present study showed that DPHC modulated calcium transit through AchR and VEGFR2, increasing endothelial-dependent NO production. Thus, DPHC, a natural marine component, can efficiently ameliorate cardiovascular diseases by improving vascular function.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Phaeophyceae/química , Vasodilatadores/farmacologia , Animais , Animais Geneticamente Modificados , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Humanos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Colinérgicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/isolamento & purificação , Peixe-Zebra
16.
Antioxidants (Basel) ; 10(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466611

RESUMO

A comprehensive antioxidant evaluation was performed on enzymatic hydrolysates of Stichopus japonicus (S. japonicus) using Vero cells and zebrafish models for in vitro and in vivo studies, respectively. S. japonicus was hydrolyzed with food-grade enzymes (alcalase, α-chymotrypsin, flavourzyme, kojizyme, neutrase, papain, pepsin, protamex, and trypsin), and the free radical scavenging activities were screened via electron spin resonance (ESR) spectroscopy. According to the results, the enzymatic hydrolysates contained high protein and relatively low polysaccharide and sulfate contents. Among these hydrolysates, the α-chymotrypsin assisted hydrolysate from S. japonicus (α-chy) showed high yield and protein content, and strong hydroxyl radical scavenging activity. Therefore, α-chy was chosen for further purification. The α-chy was fractionated by ultrafiltration into three ultrafiltration (UF) fractions based on their molecular weight: >10 kDa (α-chy-I), 5-10 kDa (α-chy-II), and <5 kDa (α-chy-III), and we evaluated their antioxidant properties in H2O2 exposed Vero cells. The α-chy and its UF fractions significantly decreased the intracellular reactive oxygen species (ROS) generation and increased cell viability in H2O2 exposed Vero cells. Among them, α-chy-III effectively declined the intracellular ROS levels and increased cell viability and exhibited protection against H2O2 induced apoptotic damage. Furthermore, α-chy-III remarkably attenuated the cell death, intracellular ROS and lipid peroxidation in H2O2 exposed zebrafish embryos. Altogether, our findings demonstrated that α-chy and its α-chy-III from S. japonicus possess strong antioxidant activities that could be utilized as a bioactive ingredient for functional food industries.

17.
Mar Drugs ; 18(12)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33317054

RESUMO

Fucosterol is a phytosterol that is abundant in marine brown algae and is a renowned secondary metabolite. However, its ability to protect macrophages against particulate matter (PM) has not been clarified with regard to inflammation; thus, this study aimed to illustrate the above. Padina boryana, a brown algae that is widespread in Indo-Pacific waters, was applied in the isolation of fucosterol. Isolation was conducted using silica open columns, while identification was assisted with gas chromatography-mass spectroscopy (GC-MS) and NMR. Elevated levels of PM led the research objectives toward the implementation of it as a stimulant. Both inflammation and oxidative stress were caused due the fact of its effect. RAW 264.7 macrophages were used as a model system to evaluate the process. It was apparent that the increased NO production levels, due to the PM, were mediated through the inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and pro-inflammatory cytokines (i.e., interleukin-6 (IL-6), interleukin-1 (IL-1ß) and tumor necrosis factor-α (TNF-α), including prostaglandin E2 (PGE2)). Further, investigations provided solid evidence regarding the involvement of NF-κB and mitogen-activated protein kinases (MAPKs) in the process. Oxidative stress/inflammation which are inseparable components of the cellular homeostasis were intersected through the Nrf2/HO-1 pathway. Conclusively, fucosterol is a potent protector against PM-induced inflammation in macrophages and hence be utilized as natural product secondary metabolite in a sustainable manner.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Heme Oxigenase-1/metabolismo , Macrófagos/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Phaeophyceae , Estigmasterol/análogos & derivados , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Citocinas/genética , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/enzimologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Phaeophyceae/química , Fosforilação , Células RAW 264.7 , Transdução de Sinais , Estigmasterol/isolamento & purificação , Estigmasterol/farmacologia
18.
Mar Drugs ; 18(9)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957728

RESUMO

Diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae (IO) showed potential whitening effects against UV-B radiation. However, the components of IO as well as their molecular mechanism against α-melanocyte-stimulating hormone (α-MSH) have not yet been investigated. Thus, this study aimed to investigate the inhibitory effects of Ishophloroglucin A (IPA), a phlorotannin isolated from brown algae IO, and its crude extract (IOE), in melanogenesis in vivo in an α-MSH-induced zebrafish model and in B16F10 melanoma cells in vitro. Molecular docking studies of the phlorotannins were carried out to determine their inhibitory effects and to elucidate their mode of interaction with tyrosinase, a glycoprotein related to melanogenesis. In addition, morphological changes and melanin content decreased in the α-MSH-induced zebrafish model after IPA and IOE treatment. Furthermore, Western blotting results revealed that IPA upregulated the extracellular related protein expression in α-MSH-stimulated B16F10 cells. Hence, these results suggest that IPA isolated from IOE has a potential for use in the pharmaceutical and cosmetic industries.


Assuntos
Benzofuranos/farmacologia , Dioxinas/farmacologia , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Phaeophyceae/metabolismo , Preparações Clareadoras de Pele/farmacologia , alfa-MSH/farmacologia , Animais , Benzofuranos/isolamento & purificação , Dioxinas/isolamento & purificação , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Fosforilação , Preparações Clareadoras de Pele/isolamento & purificação , Peixe-Zebra , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Antioxidants (Basel) ; 9(8)2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-32784879

RESUMO

Sulfated polysaccharides prepared from marine algae are potential ingredients in nutraceutical, pharmaceutical, and cosmeceutical industries. In the present study, the antioxidant, anti-melanogenesis, and photoprotective effects of sulfated polysaccharides obtained from Ecklonia maxima (EMC) were investigated to evaluate their potential in cosmetic. EMC was successfully prepared through Celluclast-assisted extraction and ethanol precipitation, and it contained 79.88% of sulfated polysaccharides that with 69.37% carbohydrates and 10.51% sulfate. EMC effectively suppressed 2,2-azobis(2-amidinopropane) hydrochloride (AAPH)-induced oxidative stress in vitro in Vero cells and in vivo in zebrafish. Furthermore, EMC significantly inhibited mushroom tyrosinase and reduced melanin synthesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 cells. In addition, EMC remarkably attenuated photodamage induced by UVB irradiation in vitro in human keratinocytes (HaCaT cells) and in vivo in zebrafish. Furthermore, EMC effectively inhibited wrinkle-related enzymes and improved collagen synthesis in UVB-irradiated human dermal fibroblasts (HDF cells). These results indicate that EMC possesses strong antioxidant, anti-melanogenesis, and photoprotective activities, and suggest that EMC may be an ideal ingredient in the pharmaceutical and cosmeceutical industries.

20.
Molecules ; 25(10)2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32438702

RESUMO

Fucoidan is a fucose-enriched polysaccharide, obtained from brown algae, with demonstrated antioxidant properties. However, traditional extraction methods using water or chemical-based extraction methods have reduced yield and produced hazardous by-products. In this study, we isolated fucoidan at a high yield using enzyme-assisted extraction; the Celluclast enzyme assisted extract of Undaria pinnatifida sporophylls (FCUS). To examine the antioxidant properties of FCUS, oxidative stress was induced with 2,2'-azobis (2-methylpropionamidine) dihydrochloride (AAPH) in Vero cells and zebrafish model. FCUS was composed of 30.4% sulfate and 52.3% fucose. Pre-treatment of Vero cells with FCUS dose dependently inhibited AAPH-induced reactive oxygen species (ROS) production. Moreover, FCUS remarkably reduced cell death, ROS generation, and lipid peroxidation production in zebrafish larvae. Overall, these findings indicate that the sulfate-rich fucoidan of FCUS, obtained with an eco-friendly process, could be implemented as a beneficial antioxidant agent in the functional food industry.


Assuntos
Antioxidantes/química , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/química , Undaria/química , Amidinas/toxicidade , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Chlorocebus aethiops , Peroxidação de Lipídeos/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Espécies Reativas de Oxigênio/química , Células Vero , Peixe-Zebra
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