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1.
Int J Mol Sci ; 25(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674060

RESUMO

Mandarin peel, a main by-product from the processing of citrus juice, has been highlighted for its various bioactivities and functional ingredients. Our previous study proved the inhibitory effects of Celluclast extract from mandarin peel (MPCE) on lipid accumulation and differentiation in 3T3-L1 adipocytes. Therefore, the current study aimed to evaluate the anti-obesity effect of MPCE in high-fat diet (HFD)-induced obese mice. The high-performance liquid chromatography (HPLC) analysis exhibited that narirutin and hesperidin are the main active components of MPCE. Our current results showed that MPCE supplementation decreased adiposity by reducing body and organ weights in HFD-induced obese mice. MPCE also reduced triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and leptin contents in the serum of HFD-fed mice. Moreover, MPCE significantly inhibited hepatic lipid accumulation by regulating the expression levels of proteins associated with lipid metabolism, including sterol regulatory element-binding protein (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Furthermore, MPCE administration significantly inhibited both adipogenesis and lipogenesis, with modulation of energy metabolism by activating 5' adenosine monophosphate-activated protein kinase (AMPK) and lipolytic enzymes such as hormone-sensitive lipase (HSL) in the white adipose tissue (WAT). Altogether, our findings indicate that MPCE improves HFD-induced obesity and can be used as a curative agent in pharmaceuticals and nutraceuticals to alleviate obesity and related disorders.


Assuntos
Adipogenia , Citrus , Dieta Hiperlipídica , Dissacarídeos , Metabolismo Energético , Flavanonas , Camundongos Endogâmicos C57BL , Obesidade , Extratos Vegetais , Animais , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Obesidade/etiologia , Citrus/química , Camundongos , Metabolismo Energético/efeitos dos fármacos , Extratos Vegetais/farmacologia , Masculino , Adipogenia/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Células 3T3-L1 , Fármacos Antiobesidade/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Triglicerídeos/metabolismo , Triglicerídeos/sangue
2.
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
3.
Mar Drugs ; 21(8)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37623739

RESUMO

The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, Gigantidas vrijenhoeki. The G. vrijenhoeki protein was hydrolyzed by various hydrolytic enzymes. The peptic hydrolysate exhibited the highest ACE-inhibitory activity and was fractionated into four molecular weight ranges by ultrafiltration. The <1 kDa fraction exhibited the highest ACE inhibitory activity and was found to have 11 peptide sequences. Among the analyzed peptides, KLLWNGKM exhibited stronger ACE inhibitory activity and an IC50 value of 0.007 µM. To investigate the ACE-inhibitory activity of the analyzed peptides, a molecular docking study was performed. KLLWNGKM exhibited the highest binding energy (-1317.01 kcal/mol), which was mainly attributed to the formation of hydrogen bonds with the ACE active pockets, zinc-binding motif, and zinc ion. These results indicate that G. vrijenhoeki-derived peptides can serve as nutritional and pharmacological candidates for controlling blood pressure.


Assuntos
Mytilidae , Peptidil Dipeptidase A , Animais , Simulação de Acoplamento Molecular , Peptídeos/farmacologia , Zinco
4.
Mar Drugs ; 21(7)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37504900

RESUMO

Microalgae are proposed to have powerful applications for human health in the pharmaceutical and food industries. Tetraselmis species (sp.), which are green microalgae, were identified as a source of broad-spectrum health-promoting biological activities. However, the bioactivity of these species has not been elucidated. We aimed to confirm the antioxidant, antiviral, and anti-inflammatory effects of Tetraselmis sp. extract (TEE). TEE showed 2,2-diphenyl-1-picryl-hydrazyl-hydrate radical and hydrogen peroxide scavenging activities and reduced plaque formation in Vero E6 cells infected with vaccinia virus. TEE treatment also significantly inhibited nitric oxide (NO) production and improved cell viability in lipopolysaccharide (LPS)-induced RAW264.7 cells. These anti-inflammatory effects were further analyzed in LPS-induced RAW 264.7 cells and the zebrafish model. Further, TEE reduced induced NO synthase expression and proinflammatory cytokine release, including tumor necrosis factor-α, interleukin-6, and interleukin-1ß, through MAPKs and NF-κB-dependent mechanisms. Further analysis revealed that TEE increased the survival rate and reduced cell death and NO production in an LPS-stimulated zebrafish model. Further, high-performance liquid chromatography revealed a strong presence of the carotenoid lutein in TEE. Overall, the results suggest that lutein-enriched TEE may be a potent antioxidant, antiviral, and anti-inflammatory agent that could be sustainably utilized in industrial applications.


Assuntos
Antioxidantes , Luteína , Animais , Camundongos , Humanos , Antioxidantes/farmacologia , Luteína/farmacologia , Luteína/metabolismo , Peixe-Zebra/metabolismo , Lipopolissacarídeos/farmacologia , Antivirais/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Células RAW 264.7 , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo
5.
Appl Radiat Isot ; 199: 110881, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37267776

RESUMO

Thymus quinquecostatus Celak (TQC) is an aromatic herb, that possesses a wide range of biological properties. In the present study, we investigated the radio-protective effect of TQC water extract (TQCW) in gamma ray-exposed splenocytes, a peripheral immune cell and mice. Our results showed that the treatment with TQCW dose-dependently increased the viability of splenocytes. TQCW significantly increased the proliferation of splenocytes by reducing the production of intracellular reactive oxygen species (ROS) in 2 Gy-exposed splenocytes. Moreover, TQCW enhanced the hemopoietic system as increasing the number of endogenous spleen colony-forming units, and the number and the proliferation of splenocytes in 7 Gy-exposed mice. These results suggest that TQCW protects mice by enhancing the splenocytes proliferation and hemopoietic systems following exposure to gamma rays.


Assuntos
Produtos Biológicos , Thymus (Planta) , Animais , Camundongos , Espécies Reativas de Oxigênio
6.
Food Chem Toxicol ; 177: 113864, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37263571

RESUMO

Recently, a new mechanism has revealed that gut microbiota plays a pivotal role in metabolizing fructose to acetate that facilitates hepatic lipogenesis. Therefore, our study investigated the role of microbiome on abnormal lipid synthesis in the presence of fructose and identified attenuating effects of Ishige okamurae Celluclast extract (IOCE) against fructose-induced fatty liver. The results indicated that oral administration of IOCE (150 and 300 mg/kg/day for 12 weeks) significantly reduced both gut microbiota-mediated and -non-mediated hepatic lipogenesis simultaneously triggered by fructose metabolism. IOCE reduced hepatic triglyceride accumulation and expression levels of key enzymes for glucolipid metabolism. In addition, IOCE regulated fatty acid synthesis, ß-oxidation, and improved hepatic inflammation. Furthermore, IOCE inhibited direct fructose-to-acetate conversion and altered the compositions of gut microbiota. These findings suggest that IOCE might serve as a potential prebiotic dietary supplement by ameliorating fatty liver through dual regulation of classical lipogenic pathway and gut microbiota.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Metabolismo dos Lipídeos , Frutose/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta , Fígado , Acetatos/farmacologia , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica
7.
Food Sci Anim Resour ; 43(1): 184-194, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36789190

RESUMO

Recently, interest in food-derived bioactive peptides as promising ingredients for the prevention and improvement of hypertension is increasing. The purpose of this study was to determine the structure and antihypertensive effect of an antioxidant peptide purified from velvet antler in a previous study and evaluate its potential as a various bioactive peptide. Molecular weight (MW) and amino acid sequences of the purified peptide were determined by quadrupole time-of-flight electrospray ionization mass spectroscopy. The angiotensin I-converting enzyme (ACE) inhibition activity of the purified peptide was assessed by enzyme reaction methods and in silico molecular docking analysis to determine the interaction between the purified peptide and ACE. Also, antihypertensive effect of the purified peptide in spontaneously hypertensive rats (SHRs) was investigated. The purified antioxidant peptide was identified to be a pentapeptide Asp-Asn-Arg-Tyr-Tyr with a MW of 730.31 Da. This pentapeptide showed potent inhibition activity against ACE (IC50 value, 3.72 µM). Molecular docking studies revealed a good and stable binding affinity between purified peptide and ACE and indicated that the purified peptide could interact with HOH2570, ARG522, ARG124, GLU143, HIS387, TRP357, and GLU403 residues of ACE. Furthermore, oral administration of the pentapeptide significantly reduced blood pressure in SHRs. The pentapeptide derived from enzymatic hydrolysate of velvet antler is an excellent ACE inhibitor. It might be effectively applied as an animal-based functional food ingredient.

8.
Fitoterapia ; 163: 105342, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36330897

RESUMO

Ishophloroglucin A (IPA) is one of the most abundant and active compounds in Ishige okamurae and is known to be a potential therapeutic candidate for the improvement of metabolic diseases. However, IPA on the inhibitory effects of protein tyrosine phosphatase 1B (PTP1B) and adipogenesis have not been determined. In this study, we investigated the effects of IPA on the inhibition of PTP1B, the effects on adipogenesis, and its mechanisms of action in 3 T3-L1 adipocytes. The IC50 value of IPA against PTP1B was 0.43 µM, which evidenced the higher inhibition activity than that of ursolic acid, a known PTP1B inhibitor. For further insight, we predicted the 3D structure of PTP1B and used a docking algorithm to simulate the binding between PTP1B and IPA. Molecular docking studies revealed a high and stable binding affinity between IPA and PTP1B and indicated that the IPA could interacts with the amino acid residues located in a region to the active site of PTP1B. Further studies showed that IPA concentrations between 6.25 µM and 25 µM dose-dependently attenuated adipogenesis, which was accompanied by a reduction in adipogenesis-related factors, including PPARγ, C/EBPα, SREBP-1c, and FABP4. Our findings suggested that IPA may be a promising natural compound for the treatment of obesity and related diseases.


Assuntos
Adipogenia , Phaeophyceae , Camundongos , Animais , Células 3T3-L1 , Simulação de Acoplamento Molecular , Estrutura Molecular , Adipócitos , Phaeophyceae/química , Inibidores Enzimáticos/farmacologia
9.
Mar Drugs ; 19(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34677466

RESUMO

Turbo cornutus, the horned turban sea snail, is found along the intertidal and basaltic shorelines of Jeju Island, Korea. T. cornutus feeds on seaweeds (e.g., Undaria sp., and Ecklonia sp.) composed of diverse antioxidants. This study identified potential antioxidant properties from T. cornutus viscera tissues. Diverse extracts were evaluated for their hydrogen peroxide (H2O2) scavenging activities. T. cornutus viscera protamex-assisted extracts (TVP) were purified by gel filtration chromatography (GFC), and potential antioxidant properties were analyzed for their amino acid sequences and its peroxidase inhibition effects by in silico molecular docking and in vitro analysis. According to the results, T. cornutus viscera tissues are composed of many protein contents with each over 50%. Among the extracts, TVP possessed the highest H2O2 scavenging activity. In addition, TVP-GFC-3 significantly decreased intracellular reactive oxygen species (ROS) levels and increased cell viability in H2O2-treated HepG2 cells without cytotoxicity. TVP-GFC-3 comprises nine low molecular bioactive peptides (ELR, VGPQ, TDY, ALPHA, PAH, VDY, WSDK, VFSP, and FAPQY). Notably, the peptides dock to the active site of the myeloperoxidase (MPO), especially TDY and FAPQY showed the MPO inhibition effects with IC50 values of 646.0 ± 45.0 µM and 57.1 ± 17.7 µM, respectively. Altogether, our findings demonstrated that T. cornutus viscera have potential antioxidant properties that can be used as high value-added ingredients.


Assuntos
Antioxidantes/farmacologia , Sequestradores de Radicais Livres/farmacologia , Caramujos , Animais , Antioxidantes/química , Organismos Aquáticos , Células Hep G2/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio , Simulação de Acoplamento Molecular , Vísceras/química
10.
Fitoterapia ; 152: 104921, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33984434

RESUMO

Accumulating evidence has shown an association between osteoporosis and oxidative damage. In the present study, the protective effects of diphlorethohydroxycarmalol (DPHC) isolated from the brown algae Ishige okamurae against H2O2-induced oxidative damage via bone morphogenetic protein 2 (BMP2)/ runt-related transcription factor 2 (Runx2) signaling were investigated using MC3T3-E1 osteoblastic cells. DPHC counteracted the reduction in cell viability caused by H2O2 exposure and protected against H2O2-induced dysfunction, demonstrated by improved cellular alkaline phosphatase (ALP) activity and calcium deposition. In addition, treatment with 0.05-0.2 mM DPHC elevated the protein expression of osteoblast differentiation factors type 1 collagen, ALP, p-Smad1/5, Osterix, BMP2, and Runx2, in response to H2O2-induced oxidative damage. Importantly, DPHC decreased the expression levels of receptor activator of nuclear factor kappa-B ligand, which promotes bone resorption, and inhibited the H2O2-induced generation of reactive oxygen species. Taken together, the results suggest that DPHC counteracts the effects of oxidative stress in osteoblastic cells and has the potential to be effective in preventing and alleviating osteoporosis.


Assuntos
Compostos Heterocíclicos com 3 Anéis/farmacologia , Osteoblastos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Phaeophyceae/química , Transdução de Sinais , Células 3T3 , Animais , Proteína Morfogenética Óssea 2 , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Peróxido de Hidrogênio , Camundongos , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , República da Coreia
11.
Int J Mol Sci ; 22(8)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917915

RESUMO

Protocatechuic aldehyde (PA) is a naturally occurring phenolic compound that is a potent inhibitor of mushroom tyrosinase. However, the molecular mechanisms of the anti-melanogenesis activity of PA have not yet been reported. The aim of the current study was to clarify the melanogenesis inhibitory effects of PA and its molecular mechanisms in murine melanoma cells (B16F10). We first predicted the 3D structure of tyrosinase and used a molecular docking algorithm to simulate binding between tyrosinase and PA. These molecular modeling studies calculated a binding energy of -527.42 kcal/mol and indicated that PA interacts with Cu400 and 401, Val283, and His263. Furthermore, PA significantly decreased α-MSH-induced intracellular tyrosinase activity and melanin content in a dose-dependent manner. PA also inhibited key melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH-stimulated B16F10 cells. In addition, PA decreased MITF expression levels by inhibiting phosphorylation of cAMP response element-binding protein (CREB) and cAMP-dependent protein kinase A (PKA). These results demonstrate that PA can effectively suppress melanin synthesis in melanoma cells. Taken together, our results show that PA could serve as a potential inhibitor of melanogenesis, and hence could be explored as a possible skin-lightening agent.


Assuntos
Benzaldeídos/farmacologia , Catecóis/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melaninas/biossíntese , Fator de Transcrição Associado à Microftalmia/genética , alfa-MSH/metabolismo , Animais , Benzaldeídos/química , Catecóis/química , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/genética , Melanoma Experimental , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo
12.
Mar Drugs ; 19(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33557339

RESUMO

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity.


Assuntos
Adipogenia/efeitos dos fármacos , Clorofila/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Alga Marinha , Células 3T3-L1 , Animais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Clorofila/análogos & derivados , Clorofila/uso terapêutico , Cromatografia Líquida de Alta Pressão , Regulação para Baixo , Proteínas de Ligação a Ácido Graxo/genética , Camundongos , Obesidade/tratamento farmacológico , PPAR gama/genética , Alga Marinha/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
13.
Cell Biochem Funct ; 39(4): 546-554, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33474761

RESUMO

Diphlorethohydroxycarmalol (DPHC) is a marine polyphenolic compound derived from brown alga Ishige okamurae. A previously study has suggested that DPHC possesses strong mushroom tyrosinase inhibitory activity. However, the anti-melanogenesis effect of DPHC has not been reported at cellular level. The objective of the present study was to clarify the melanogenesis inhibitory effect of DPHC and its molecular mechanisms in murine melanoma cells (B16F10) and zebrafish model. DPHC significantly inhibited tyrosinase activity and melanin content dose-dependently in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. This polyphenolic compound also suppressed the expression of phosphorylation of cAMP response element-binding protein (CREB) by attenuating phosphorylation of cAMP-dependent protein kinase A, resulting in decreased MITF expression levels. Furthermore, DPHC downregulated MITF protein expression levels by promoting the phosphorylation of extracellular signal-regulated kinase. It also inhibited tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH stimulated B16F10 cells. In in vivo studies using zebrafish, DPHC also markedly inhibited melanin synthesis in a dose-dependent manner. These results demonstrate that DPHC can effectively inhibit melanogenesis in melanoma cells in vitro and in zebrafish in vivo, suggesting that DPHC could be applied in fields of pharmaceutical and cosmeceuticals as a skin-whitening agent. Significance of study: The present study showed for the first time that DPHC could inhibit a-MSH-stimulated melanogenesis via PKA/CREB and ERK pathway in melanoma cells. It also could inhibit pigmentation in vivo in a zebrafish model. This evidence suggests that DPHC has potential as a skin whitening agent. Taken together, DPHC could be considered as a novel anti-melanogenic agent to be applied in cosmetic, food, and medical industry.


Assuntos
Antineoplásicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Melanoma/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/antagonistas & inibidores , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Fator de Transcrição Associado à Microftalmia/antagonistas & inibidores , Fator de Transcrição Associado à Microftalmia/metabolismo , Estrutura Molecular , Phaeophyceae/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Peixe-Zebra/embriologia , alfa-MSH/antagonistas & inibidores , alfa-MSH/metabolismo
14.
Int J Mol Sci ; 21(13)2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32610570

RESUMO

Ultraviolet radiation (UV) is a major causative factor of DNA damage, inflammatory responses, reactive oxygen species (ROS) generation and a turnover of various cutaneous lesions resulting in skin photoaging. The purpose of this study is to investigate the protective effect of protocatechuic aldehyde (PA), which is a nature-derived compound, against UVA-induced photoaging by using human dermal fibroblast (HDF) cells. In this study, our results indicated that PA significantly reduced the levels of intracellular ROS, nitric oxide (NO), and prostaglandins-E2 (PGE2) in UVA-irradiated HDF cells. It also inhibited the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Besides, PA significantly suppressed the expression of matrix metalloproteinases-1 (MMP-1) and pro-inflammatory cytokines and promoted collagen synthesis in the UVA-irradiated HDF cells. These events occurred through the regulation of activator protein 1 (AP-1), nuclear factor-κB (NF-κB), and p38 signaling pathways in UVA-irradiated HDF cells. Our findings suggest that PA enhances the protective effect of UVA-irradiated photoaging, which is associated with ROS scavenging, anti-wrinkle, and anti-inflammatory activities. Therefore, PA can be a potential candidate for the provision of a protective effect against UVA-stimulated photoaging in the pharmaceutical and cosmeceutical industries.


Assuntos
Benzaldeídos/farmacologia , Catecóis/farmacologia , Fibroblastos/efeitos dos fármacos , Envelhecimento da Pele/fisiologia , Anti-Inflamatórios/farmacologia , Benzaldeídos/metabolismo , Catecóis/metabolismo , Linhagem Celular , China , Dinoprostona/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pele/metabolismo , Pele/fisiopatologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Raios Ultravioleta/efeitos adversos
15.
Mar Drugs ; 17(11)2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31717668

RESUMO

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases.


Assuntos
Fármacos Antiobesidade/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Obesidade/tratamento farmacológico , Phaeophyceae/metabolismo , Tecido Adiposo/efeitos dos fármacos , Administração Oral , Animais , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/isolamento & purificação , Dieta Hiperlipídica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/fisiopatologia , Aumento de Peso/efeitos dos fármacos
16.
Int J Mol Sci ; 20(20)2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31635129

RESUMO

Velvet antler has a long history in traditional medicine. It is also an important healthy ingredient in food as it is rich in protein. However, there has been no report about antioxidant peptides extracted from velvet antler by enzymatic hydrolysis. Thus, the objective of this study was to hydrolyze velvet antler using different commercial proteases (Acalase, Neutrase, trypsin, pepsin, and α-chymotrypsin). Antioxidant activities of different hydrolysates were investigated using peroxyl radical scavenging assay by electron spin resonance spectrometry. Among all enzymatic hydrolysates, Alcalase hydrolysate exhibited the highest peroxyl radical scavenging activity. Alcalase hydrolysate was then purified using ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. The purified peptide was identified to be Trp-Asp-Val-Lys (tetrapeptide) with molecular weight of 547.29 Da by Q-TOF ESI mass spectroscopy. This purified peptide exhibited strong scavenging activity against peroxyl radical (IC50 value, 0.028 mg/mL). In addition, this tetrapeptide showed significant protection ability against AAPH-induced oxidative stress by inhibiting of reactive oxygen species (ROS) generation in Chang liver cells in vitro and in a zebrafish model in vivo. This research suggests that the tetrapeptide derived from Alcalase-proteolytic hydrolysate of velvet antler are excellent antioxidants and could be effectively applied as functional food ingredients and pharmaceuticals.


Assuntos
Antioxidantes/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Subtilisinas/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Chifres de Veado/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Hidrólise , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra
17.
J Food Biochem ; 43(7): e12833, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31353700

RESUMO

Seahorses, Hippocampus abdominalis, have a long history in traditional Chinese medicine as an important healthy ingredient in foods. This study evaluated the antioxidant activity of an enzymatic hydrolysate prepared from a seahorse bred in Jeju, South Korea. Experiments were performed in vitro using electron spin resonance spectrometry (ESR) to determine the free radical scavenging activity and in vivo using a zebrafish model to determine the protective effects against 2,2-azobis hydrochloride (AAPH)-induced oxidative damage. H. abdominalis protein hydrolysate (HPH) exhibited peroxyl radical scavenging activity (IC50  = 0.58 mg/ml) generated by the water-soluble AAPH (azo initiator of peroxyl radicals). HPH reduced dose-dependently both intracellular reactive oxygen species (ROS) levels in AAPH-induced cells and cell death in AAPH-induced zebrafish embryos. The antioxidant peptide purified from HPH was identified as a tripeptide (alanine-glycine-aspartic acid) using Q-TOF ESI mass spectroscopy. Thus, this study demonstrated that HPH contains antioxidant peptides that exhibit a strong antioxidant activity. PRACTICAL APPLICATIONS: Hippocampus abdominalis is one of the largest seahorse species and cultivated in many countries. Because of its large body size compared to other seahorse species, H. abdominalis has acquired considerable consumer attraction in the global market. Owing to its biologically useful properties, it recently gained attention as the natural products obtained from H. abdominalis have varied applications in the field of medicine, health care products, and functional foods. Thus, commercial products of this particular seahorse species are popular among customers, especially in China. The purpose of this study was to evaluate the antioxidant property of H. abdominalism, cultured in a commercial seahorse farm in Jeju Island. Owing to its prominent antioxidant activity, it could be used as an ingredient in medicinal preparations, nutraceuticals, and functional foods.


Assuntos
Sequestradores de Radicais Livres/química , Hidrolisados de Proteína/farmacologia , Smegmamorpha/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Aquicultura , Chlorocebus aethiops , Suplementos Nutricionais , Espectroscopia de Ressonância de Spin Eletrônica , Sequestradores de Radicais Livres/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Hidrolisados de Proteína/química , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Subtilisinas/química , Subtilisinas/farmacologia , Células Vero , Peixe-Zebra
18.
Mar Drugs ; 17(1)2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30634617

RESUMO

The purpose of this study was to investigate the antiobesity effect and the mechanism of action of diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae in 3T3-L1 cells. The antiobesity effects were examined by evaluating intracellular fat accumulation in Oil Red O-stained adipocytes. Based on the results, DPHC dose-dependently inhibited the lipid accumulation in 3T3-L1 adipocytes. DPHC significantly inhibited adipocyte-specific proteins such as SREBP-1c, PPARγ, C/EBP α, and adiponectin, as well as adipogenic enzymes, including perilipin, FAS, FABP4, and leptin in adipocytes. These results indicated that DPHC primarily acts by regulating adipogenic-specific proteins through inhibiting fat accumulation and fatty acid synthesis in adipocytes. DPHC treatment significantly increased both AMPK and ACC phosphorylation in adipocytes. These results indicate that DPHC inhibits the fat accumulation by activating AMPK and ACC in 3T3-L1 cells. Taken together, these results suggest that DPHC can be used as a potential therapeutic agent against obesity.


Assuntos
Adenilato Quinase/metabolismo , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Células 3T3-L1 , Adenilato Quinase/genética , Animais , Sobrevivência Celular , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/química , Camundongos , Estrutura Molecular , Alga Marinha/química
19.
Phytother Res ; 33(3): 737-744, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30570192

RESUMO

The aim of the present study was to investigate the effect of 5-bromo-3,4-dihydroxybenzaldehyde (BD) isolated from Polysiphonia morrowii on adipogenesis and differentiation of 3T3-L1 preadipocytes into mature adipocytes and its possible mechanism of action. Levels of lipid accumulation and triglyceride were significantly lower in BD treated cells than those in untreated cells. In addition, BD treatment reduced protein expression levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding proteins α, and sterol regulatory element-binding protein 1 compared with control (no treatment). It also reduced expression levels of adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. AMP-activated protein kinase activation was found to be one specific mechanism involved in the effect of BD. These results demonstrate that BD possesses inhibitory effect on adipogenesis through activating AMP-activated protein kinase signal pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Adipogenia/efeitos dos fármacos , Benzaldeídos/farmacologia , Rodófitas/química , Células 3T3-L1 , Animais , Benzaldeídos/isolamento & purificação , Diferenciação Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Transdução de Sinais/efeitos dos fármacos
20.
Int J Mol Sci ; 19(9)2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201926

RESUMO

Marine-derived extract and/or bioactive compounds have attracted increasing demand due to their unique and potential uses as cures for various inflammation-based diseases. Several studies revealed anti-inflammatory candidates found in soft corals. However, the effects of soft corals on inflammation in an in vivo model remain to be determined. Therefore, the extract of soft coral Dendronephthya puetteri (DPE) was investigated for an in vivo anti-inflammatory effect in a lipopolysaccharide (LPS)-stimulated zebrafish model to determine its potential use as a natural anti-inflammatory agent. We also investigated whether DPE has toxic effects in a zebrafish model. No significant changes were observed in terms of survival, heart beat rate, or developmental abnormalities in the zebrafish embryos exposed to a concentration below 100 µg/mL of DPE. Treating the zebrafish model with LPS-treatment significantly increased the ROS, NO generation, and cell death. However, DPE inhibited this LPS-stimulated ROS, NO generation, and cell death in a dose-dependent manner. In addition, DPE significantly reduced the mRNA expression of both iNOS and COX-2 and markedly suppressed the expression levels of the proinflammatory cytokines, TNF-α and IL-6, in an LPS-stimulated zebrafish model. These findings demonstrate that DPE has profound anti-inflammatory effect in vivo, suggesting that DPE might be a strong natural anti-inflammatory agent.


Assuntos
Antozoários/química , Produtos Biológicos/administração & dosagem , Inflamação/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Animais , Produtos Biológicos/farmacologia , Morte Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Inflamação/induzido quimicamente , Inflamação/imunologia , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra
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