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1.
Chem Biodivers ; 21(6): e202301509, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38594219

RESUMO

Neurodegenerative diseases are characterized by the progressive loss of selectively vulnerable populations of neurons, and many factors are involved in its causes. Neurotoxicity and oxidative stress, are the main related factors. The octapeptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) was identified from the microalgae Isochrysis zhanjiangensis and exhibited potential anti-oxidative stress activity. In this study, the stability of α-synaptic protein binding to IEC was modeled using molecular dynamics, and the results indicated binding stabilization within 60 ns. Oxidative stress in neurons is the major cause of α-synaptic protein congestion. Therefore, we next evaluated the protective effects of IEC against oxidative stress and neurotoxicity in 6-ohdainduced Parkinson's disease (PD) model SH-SY5Y cells in vitro. In oxidative stress, IEC appeared to increase the expression of the antioxidant enzymes HO-1 and GPX through the antioxidant pathway of Nrf2, and molecular docking of IEC with Nrf2 and GPX could generate hydrogen bonds. Regarding apoptosis, IEC protected cells by increasing the Bcl-2/Bax ratio, inhibiting the caspase cascade, acting on p53, and modulating the Jak2/Stat3 pathway. The results indicated that IEC exerted neuroprotective effects through the inhibition of α-synaptic protein aggregation and antioxidant activity. Therefore, microalgal peptides have promising applications in the prevention and treatment of neurodegenerative diseases.


Assuntos
Janus Quinase 2 , Microalgas , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Oxidopamina , Fator de Transcrição STAT3 , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Janus Quinase 2/metabolismo , Janus Quinase 2/antagonistas & inibidores , Microalgas/química , Microalgas/metabolismo , Oxidopamina/farmacologia , Oxidopamina/antagonistas & inibidores , Heme Oxigenase-1/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Oligopeptídeos/farmacologia , Oligopeptídeos/química , Transdução de Sinais/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos
2.
Molecules ; 29(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38338436

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the elderly for which there is no cure or disease-modifying therapy. Mitochondrial dysfunction and oxidative stress play a central role in dopaminergic neurodegeneration in PD. Therefore, antioxidants are considered a promising neuroprotective approach. In in vivo activity studies, 6-OHDA-induced oxidative stress in SH-SY5Y cells was established as a model of PD for cellular experiments. IIAVE (Ile-Ile-Ala-Val-Glu) was derived from Isochrysis zhanjiangensis octapeptide (IIAVEAGC), which has a small molecular weight. The structure and antioxidant activity of IIAVE were tested in a previous study and proved to have good antioxidant potential. In this study, the chemical properties of IIAVE were calculated using quantum chemical methods, including frontier molecular orbital (FMO), molecular electrostatic potential (MEP), natural population analysis (NPA), and global reactivity properties. The interaction of IIAVE with Bcl-2 and DJ-1 was investigated using the molecular docking method. The results showed that IIAVE promoted the activation of the Keap1/Nrf2 pathway and up-regulated the expression of the superoxide dismutase 1 (SOD-1) protein by inhibiting the level of reactive oxygen species (ROS) in cells. In addition, IIAVE inhibits ROS production and prevents 6-OHDA-induced oxidative damage by restoring mitochondrial membrane potential. Furthermore, IIAVE inhibited cell apoptosis by increasing the Bcl-2/Bax ratio and inhibiting the activation of Caspase-9 and Caspase-3. Thus, IIAVE may become a potential drug for the treatment and prevention of PD.


Assuntos
Haptófitas , Neuroblastoma , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Idoso , Neuroproteção , Espécies Reativas de Oxigênio/metabolismo , Oxidopamina/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Haptófitas/metabolismo , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular Tumoral , Apoptose , Antioxidantes/farmacologia , Doença de Parkinson/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
3.
Mar Drugs ; 21(3)2023 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-36976205

RESUMO

Epi-aszonalenin A (EAA) is an alkaloid that is isolated and purified from the secondary metabolites of coral symbiotic fungi and has been shown to have good atherosclerotic intervention activity and anti-angiogenic activity in our previous studies. In the present study, antiangiogenic activity was used as a basis of an intensive study of its mechanism of action against tumor metastasis and invasion. Invasive metastatic pairs are a hallmark of malignancy, and the dissemination of tumor cells is the most dangerous process in the development of tumors. The results of cell wound healing and the Transwell chamber assay showed that EAA interfered well with PMA-induced migration and invasion of HT1080 cells. Western blot and the ELISA assay showed that EAA decreased MMPs and vascular endothelial growth factor (VEGF) activity and inhibited the expression of N-cadherin and hypoxia-inducible factor-1α (HIF-1α) by regulating the phosphorylation of downstream mitogen-activated protein kinase (MAPK), PI3K/AKT, and NF-κB pathways. Simultaneous molecular docking results revealed that the mimic coupling between the EAA and MMP-2/-9 molecules formed a stable interaction. The results of this study provide a research basis for the inhibition of tumor metastasis by EAA, and together with previous studies, confirm the potential pharmacology and drug potential for this class of compound for application in angiogenesis-related diseases and further improve the availability of coral symbiotic fungi.


Assuntos
Fosfatidilinositol 3-Quinases , Fator A de Crescimento do Endotélio Vascular , Fator A de Crescimento do Endotélio Vascular/metabolismo , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Movimento Celular , Subunidade alfa do Fator 1 Induzível por Hipóxia
4.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674443

RESUMO

Alzheimer's disease (AD), a neurodegenerative disease, is the most common cause of dementia in humans worldwide. Although more in-depth research has been carried out on AD, the therapeutic effect of AD is not as expected, and natural active substances are increasingly sought after by scientists. In the present study, we evaluated two benzaldehydes from a coral-derived Aspergillus terreus strain C23-3, their anti-neuroinflammatory activity in microglia (BV-2), and their neuroprotective activity and mechanisms in hippocampal neuronal cells (HT-22). These include the protein expression of iNOS, COX-2, MAPKs pathways, Tau protein-related pathways, caspases family-related signaling pathways. They also include the levels of TNF-α, IL-6, IL-18 and ROS, as well as the level of mitochondrial oxidative stress and neuronal cell apoptosis. The results showed that both benzaldehydes were effective in reducing the secretion of various inflammatory mediators, as well as pro-inflammatory factors. Among these, benzaldehyde 2 inhibited mitochondrial oxidative stress and blocked neuronal cell apoptosis through Tau protein-related pathways and caspases family-related signaling pathways, thereby inhibiting ß-amyloid (Aß)-induced neurological damage. This study reveals that benzaldehyde 2 has potential as a therapeutic agent for Alzheimer's disease, and offers a new approach to the high-value use of marine natural products.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Proteínas tau/metabolismo , Benzaldeídos , Peptídeos beta-Amiloides/metabolismo , Caspases
5.
Environ Monit Assess ; 195(6): 634, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37133617

RESUMO

Mangroves are located at the intersection of land and sea and are also heavily affected by plastic wastes. Biofilms of plastic wastes in mangroves are reservoirs for antibiotic resistance genes (ARGs). In this study, plastic wastes and ARG pollution were investigated from three typical mangrove areas in Zhanjiang, South China. Transparent was the dominant colors of plastic wastes in three mangroves. Fragment and film shape accounted for 57.73-88.23% of plastic waste samples in mangroves. In addition, 39.50% of plastic wastes in protected area mangroves are PS. The metagenomic results shows that the 175 ARGs were found on plastic wastes of the three mangroves, the abundance accounting for 91.11% of the total ARGs. The abundance of Vibrio accounted for 2.31% of the total bacteria genera in aquaculture pond area mangrove. Correlation analysis shows that a microbe can carry multiple ARGs that may improve resistance to antibiotics. Microbes are the potential hosts of most ARGs, suggesting that ARGs can be transmitted by microbes. Because the mangroves are closely related to human activities and the high abundance of ARGs on plastic increases the ecological risks, people should improve plastic waste management and prevent the spread of ARGs by reducing plastic pollution.


Assuntos
Antibacterianos , Genes Bacterianos , Humanos , Antibacterianos/farmacologia , Plásticos , Monitoramento Ambiental , Resistência Microbiana a Medicamentos/genética
6.
Biochem Biophys Res Commun ; 634: 10-19, 2022 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-36228540

RESUMO

Extracellular vesicles (EVs) and their exosome subsets are vesicle-like nanoparticles (EVs) that are secreted by cells and contain various factors that treat various diseases. However, studies on extracting EVs from marine shellfish are still relatively lacking. In this study, EVs were isolated from Pinctada martensii mucus and the efficacy of EVs in modulating the inflammatory environment was demonstrated. A human skin inflammatory cell model was established to investigate the effect of Pinctada martensii mucus-derived EVs on inflammation. The results showed that EVs could restore the viability of inflammatory HaCaT cells and decrease the level of reactive oxygen species (ROS), as well as the mRNA expression of IL-6, IL-8 and TNF-α. The inflammation of HaCaT cells was treated by inhibiting the activation of the MAPK, NF-κB and NLRP3 inflammasome signaling pathways, which prevented the phosphorylation of related inflammatory proteins and the entry of P65 protein into the nucleus. This study provides novel EVs from marine shellfish-derived bioactive materials.


Assuntos
Dermatite , Vesículas Extracelulares , Pinctada , Animais , Humanos , Vesículas Extracelulares/metabolismo , Inflamassomos/metabolismo , Inflamação , Muco/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pinctada/metabolismo , Proteínas Quinases Ativadas por Mitógeno
7.
Plant Foods Hum Nutr ; 77(2): 181-189, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35476173

RESUMO

In the early stage, oxidized low density lipoprotein (ox-LDL) caused atherosclerosis, followed by human umbilical vein endothelial cells (HUVEC) damage, leading to a variety of cardiovascular related diseases. This study investigated the mechanism of nonapeptide (EMFGTSSET, ETT) isolated from in vitro gastrointestinal digestion of Isochrysis zhanjiang on endothelial cell inflammation and apoptosis induced by ox-LDL in atherosclerosis. At the cellular level, the results shown that ETT inhibited the up-regulation of oxidized low-density lipoprotein receptor-1 (LOX-1) induced by ox-LDL. Furthermore, ETT inhibited the fluorescence intensity of ROS, inflammatory factors (interleukin-6, interleukin-1ß, and tumor necrosis factor-α) and the expression of cell adhesion molecules (vascular cell adhesion protein 1 and intercellular cell adhesion molecule-1). In addition, it also upregulates nuclear red blood cell 2 related factor 2 (Nrf2), heme oxygenase-1 (HO -1), p-Akt, and bcl-2 levels. But down-regulated the expression of p-p65, p-IκB-α, p-p38, p-ERK, p-JNK, bax, and cleaved caspase-9/-3 (c-c-9/-3), thereby inhibited ox-LDL induction inflammation and apoptosis of atherosclerosis. Through molecular docking, it was judged that the stable interaction between ETT and LOX-1 and VCAM-1 was maintained through hydrogen bonding. These results can provide a theoretical basis for ETT as a potential substance for the prevention and treatment of atherosclerosis, and further improve the value of Isochrysis zhanjiangensis.


Assuntos
Aterosclerose , Haptófitas , Microalgas , Apoptose , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Haptófitas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/tratamento farmacológico , Lipoproteínas LDL , Microalgas/metabolismo , Simulação de Acoplamento Molecular , Receptores Depuradores Classe E/metabolismo
8.
Mar Drugs ; 19(3)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802989

RESUMO

The liver is vulnerable to oxidative stress-induced damage, which leads to many diseases, including alcoholic liver disease (ALD). Liver disease endanger people's health, and the incidence of ALD is increasing; therefore, prevention is very important. 7-phloro-eckol (7PE) is a seaweed polyphenol, which was isolated from Ecklonia cava in a previous study. In this study, the antioxidative stress effect of 7PE on HepG2/CYP2E1 cells was evaluated by alcohol-induced cytotoxicity, DNA damage, and expression of related inflammation and apoptosis proteins. The results showed that 7PE caused alcohol-induced cytotoxicity to abate, reduced the amount of reactive oxygen species (ROS) and nitric oxide (NO), and effectively inhibited DNA damage in HepG2/CYP2E1 cells. Additionally, the expression levels of glutathione (GSH), superoxide dismutase (SOD), B cell lymphoma 2 (Bcl-2), and Akt increased, while γ-glutamyltransferase (GGT), Bcl-2 related x (Bax), cleaved caspase-3, cleaved caspase-9, nuclear factor-κB (NF-κB), and JNK decreased. Finally, molecular docking proved that 7PE could bind to BCL-2 and GSH protein. These results indicate that 7PE can alleviate the alcohol-induced oxidative stress injury of HepG2 cells and that 7PE may have a potential application prospect in the future development of antioxidants.


Assuntos
Antioxidantes/farmacologia , Citocromo P-450 CYP2E1/metabolismo , Dioxinas/farmacologia , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Phaeophyceae/metabolismo , Alga Marinha/metabolismo , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Dioxinas/isolamento & purificação , Etanol/toxicidade , Células Hep G2 , Hepatócitos/enzimologia , Humanos , Mediadores da Inflamação/metabolismo , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
9.
Mar Drugs ; 19(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34822497

RESUMO

Marine microalgae can be used as sustainable protein sources in many fields with positive effects on human and animal health. DAPTMGY is a heptapeptide isolated from Isochrysis zhanjiangensis which is a microalga. In this study, we evaluated its anti-photoaging properties and mechanism of action in human immortalized keratinocytes cells (HaCaT). The results showed that DAPTMGY scavenged reactive oxygen species (ROS) and increase the level of endogenous antioxidants. In addition, through the exploration of its mechanism, it was determined that DAPIMGY exerted anti-photoaging effects. Specifically, the heptapeptide inhibits UVB-induced apoptosis through down-regulation of p53, caspase-8, caspase-3 and Bax and up-regulation of Bcl-2. Thus, DAPTMGY, isolated from I. zhanjiangensis, exhibits protective effects against UVB-induced damage.


Assuntos
Antioxidantes/farmacologia , Haptófitas , Peptídeos/farmacologia , Antioxidantes/química , Apoptose/efeitos dos fármacos , Organismos Aquáticos , Células HaCaT/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Peptídeos/química , Envelhecimento da Pele/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Raios Ultravioleta
10.
Mar Drugs ; 19(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34822505

RESUMO

Abalone viscera (AV) is one of the byproducts of the seafood processing industry. The low molecular weight (<5 kDa) peptides (LMW-AV) obtained from gastrointestinal digestion of AV could suppress allergenic responses on activated HMC-1 human mast cells in our previous study. Regarding the allergenic response of LMW-AV, in the present study, we further investigated the potential of oral administration of LMW-AV against atopic dermatitis (AD) in a dermatitis-induced model stimulated with Dermatophagoides farinae. The results demonstrated that the LMW-AV reduced a number of clinical symptoms, such as the severity of the dermatitis and serum immunoglobulin E levels. Moreover, LMW-AV could inhibit the expression of chemokines and cytokines. The histological analysis indicated that the LMW-AV has suppressed the eosinophil count and the mast cell infiltration into the upper dermis. The results suggest that LMW-AV can be considered as a promising candidate for AD treatment.


Assuntos
Antialérgicos/farmacologia , Peptídeos/farmacologia , Frutos do Mar , Animais , Antialérgicos/química , Organismos Aquáticos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Modelos Animais de Doenças , Humanos , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Peso Molecular , Peptídeos/química , Organismos Livres de Patógenos Específicos , Vísceras
11.
Ecotoxicol Environ Saf ; 227: 112885, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34634601

RESUMO

The coexistence of nanoplastics (NPs) and pollutants such as arsenic (As) has become an unignorable environmental problem. However, there is still a considerable knowledge gap about the impact of NPs and pollutants on human health risks. In this study, the human gastric adenocarcinoma (AGS) cells were used as a model to investigate the toxicity of NPs with different particle sizes and As by MTT assay, western blotting, immunofluorescence and so on. The results showed that 20 nm (8 µg/mL), 50 nm (128 µg/mL), 200 nm (128 µg/mL), 500 nm (128 µg/mL), 1000 nm (128 µg/mL) polystyrene (PS) did not affect cell viability, ROS, intracellular calcium and activate apoptosis pathway in AGS cells. However, noncytotoxic concentration of NPs enhanced the cytotoxicity and intracellular accumulation of As. NPs destroys the fluidity of cell membrane and cytoskeleton, inhibits the activity of ABC transporter, and leads to the accumulation of As in cells. This work highlights that the damage caused by NPs, especially at the level of noncytotoxicity, joint with As cannot be ignored and provides a specific toxicological mechanism of NPs accompanied by exposure to As.


Assuntos
Arsênio , Nanopartículas , Transportadores de Cassetes de Ligação de ATP , Citoesqueleto , Humanos , Microplásticos
12.
Chem Biodivers ; 17(8): e2000055, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32419273

RESUMO

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 in 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 -26.33 kcal/mol for ARA and -43.70 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 20 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.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Óleos de Plantas/farmacologia , Alga Marinha/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Cinética , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo
13.
Molecules ; 25(5)2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32106572

RESUMO

Alcoholic liver disease (ALD) threatens human health, so it is imperative that we find ways to prevent or treat it. In recent years, the study of polysaccharides has shown that they have different kinds of bioactivities. Among them are many biological effects that have been attributed to polysaccharide precursors. D-Isofloridoside (DIF) is one of the polysaccharide precursors from the marine red alga Laurencia undulata. This study evaluated the effect of DIF on alcohol-induced oxidative stress in human hepatoma cells (HepG2). As a result, DIF attenuated alcohol-induced cytotoxicity, reduced the amount of intracellular reactive oxygen species (ROS), and effectively reduced alcohol-induced DNA damage in HepG2 cells. In addition, a western blot showed that, after DIF treatment, the expression levels of glutathione (GSH), superoxide dismutase (SOD), and B-cell lymphoma-2 (bcl-2) increased, while the expression levels of γ-glutamyl transferase (GGT), BCL2-associated X (bax), cleaved caspase-3, and mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase ) signal transduction proteins reduced. This showed that DIF may protect cells by reducing the amount of intracellular ROS and inhibiting intracellular oxidative stress and apoptotic processes. Finally, molecular docking demonstrated that DIF can bind to SOD, GGT, B-cell lymphoma-2, and bax proteins. These results indicated that DIF can protect HepG2 cells from alcohol-induced oxidative stress damage, making it an effective potential ingredient in functional foods.


Assuntos
Galactosídeos/farmacologia , Laurencia/química , Hepatopatias Alcoólicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Etanol/toxicidade , Galactosídeos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/genética , Células Hep G2 , Humanos , Hepatopatias Alcoólicas/patologia , Simulação de Acoplamento Molecular , Polissacarídeos/química , Polissacarídeos/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/química
14.
J Sci Food Agric ; 100(1): 315-324, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525262

RESUMO

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50  = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Captopril/química , Hipertensão/tratamento farmacológico , Peptídeos/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Ciclídeos , Digestão , Proteínas de Peixes/química , Trato Gastrointestinal/metabolismo , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Cinética , Masculino , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Endogâmicos SHR
15.
Anal Chem ; 91(13): 8184-8191, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31140271

RESUMO

The transport of ions in nanochannels has received considerable interest owing to the unique transport properties and potential applications. In this study, ultrasmall nanochannels (0.8-1.2 nm) were fabricated in porous anodized aluminum (PAA) membrane in situ growth. 2-Methylimidazole and zinc nitrate were used as the reaction precursor solkution, and then zeolitic imidazolate framework (ZIF-8) nanoparticles were sufficiently filled in PAA nanochannels to form a ZIF-8/PAA nanochannels composite membrane. Because ZIF-8 is a microporous material and has a strong ability to adsorb heavy metals, the composite membrane was used as a biosensor to detect lead ion (Pb2+) by the coordination interaction between Pb2+ and nitrogen atoms. The detection limit reached to 0.03 nM due to the enrichment of nanochannels under electric field. The sensor has a good linear range for Pb2+ from 10 nM to 10 µM.

16.
Mar Drugs ; 17(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340575

RESUMO

Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-κB may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Hipertensão/complicações , Oligopeptídeos/farmacologia , Tilápia , Doenças Vasculares/prevenção & controle , Angiotensina II/toxicidade , Animais , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipertensão/patologia , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/química , NF-kappa B/metabolismo , Oligopeptídeos/química , Estresse Oxidativo/efeitos dos fármacos , Ligação Proteica , Transdução de Sinais/efeitos dos fármacos , Doenças Vasculares/patologia
17.
Mar Drugs ; 17(4)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022939

RESUMO

Vasculogenic mimicry (VM) formed by tumor cells plays a vital role in the progress of tumor, because it provides nutrition for tumor cells and takes away the metabolites. Therefore, the inhibition of VM is crucial to the clinical treatment of tumors. In this study, we investigated the anti-tumor effect of a novel peptide, KVEPQDPSEW (AATP), isolated from abalone (Haliotis discus hannai) on HT1080 cells by migration, invasion analysis and the mode of action. The results showed that AATP effectively inhibited MMPs by blocking MAPKs and NF-κB pathways, leading to the downregulation of metastasis of tumor cells. Moreover, AATP significantly inhibited VM and pro-angiogenic factors, including VEGF and MMPs by suppression of AKT/mTOR signaling. In addition, molecular docking was used to study the interaction of AATP and HIF-1α, and the results showed that AATP was combined with an active site of HIF-1α by a hydrogen bond. The effect of AATP on anti-metastatic and anti-vascular in HT1080 cells revealed that AATP may be a potential lead compound for treatment of tumors in the future.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia , Adulto , Inibidores da Angiogênese/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/metabolismo , NF-kappa B/metabolismo , Metástase Neoplásica , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Neoplasias/patologia , Proteína Oncogênica v-akt/metabolismo , Peptídeos/química , Peptídeos/isolamento & purificação , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Esferoides Celulares/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , eIF-2 Quinase/metabolismo
18.
Mar Drugs ; 16(6)2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29880753

RESUMO

Butyrolactone-I (ZB5-1) from the coral-derived fungus Aspergillus terreus was investigated in this study to estimate its anti-neuroinflammatory effects on lipopolysaccharide (LPS)-induced BV-2 microglia cells. MTT assay indicated that ZB5-1 in tested concentrations had no cytotoxicity on BV-2 cells, and significantly reduced the production of nitric oxide (NO), measured using Griess reagent, and interleukin-1 beta (IL-1ß), detected by enzyme-linked immunosorbent assay (ELISA). ZB5-1 also down-regulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner by Western blot analysis. Moreover, the effect of ZB5-1 on the nuclear factor-κB (NF-κB) signaling pathway was studied via the expression of phosphorylation of NF-κB p65 and inhibitor of NF-κB (IκB), and the nuclear translocation of NF-κB p65 respectively. The results showed that ZB5-1 could inhibit the phosphorylation of p65 and IκB. Furthermore, molecular docking study suggested that ZB5-1 bound at the active sites of NF-κB to prevent its translocation to the nucleus. Therefore, we suggest ZB5-1 has a potential to reduce the anti-inflammatory response in LPS-induced BV-2 cells.


Assuntos
4-Butirolactona/análogos & derivados , Antozoários/microbiologia , Aspergillus/metabolismo , Inflamação/tratamento farmacológico , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , 4-Butirolactona/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Proteínas I-kappa B/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos
19.
Curr Microbiol ; 69(4): 445-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24842302

RESUMO

A strain designated as S85(T) was isolated from a seaweed collected from coastal area of Chuuk State in Micronesia. The strain was gram-negative, rod-shaped, and non-motile and formed yellow colonies on the SWY agar (0.2 % yeast extract and 1.5 % agar in seawater) and Marine agar 2216. The strain grew at pH 5-9 (optimum, pH 8), at 15-40 °C (optimum, 25-28 °C), and with 1-9 % (w/v) NaCl (optimum, 3 %). The phylogenetic analysis based on 16S rRNA gene sequence showed that strain S85(T) was related to Lutibacter litoralis CL-TF09(T) and Maritimimonas rapanae A31(T) with 91.4 % and with 90.5 % similarity, respectively. The dominant fatty acids were iso-C15:0, iso-C15:0 3-OH and iso-C17:0 3-OH, C16:0 3-OH and summed feature 3 (C16:1 ω7c and/or iso-C15:0 2-OH). The major isoprenoid quinone was MK-6. The DNA G+C content of the type strain was 34.6 mol %. The major polar lipids were phosphatidylethanolamine, an unknown glycolipid and two unknown polar lipids. Based on this polyphasic taxonomic data, strain S85(T) stands for a novel species of a new genus, and we propose the name Ochrovirga pacifica gen. nov., sp. nov. The type strain of O. pacifica is S85(T) (=KCCM 90106 =JCM 18327(T)).


Assuntos
Flavobacteriaceae/isolamento & purificação , Água do Mar/microbiologia , Alga Marinha/microbiologia , Ágar/metabolismo , Composição de Bases , Ácidos Graxos/metabolismo , Flavobacteriaceae/classificação , Flavobacteriaceae/genética , Flavobacteriaceae/imunologia , Flavobacteriaceae/metabolismo , Micronésia , Dados de Sequência Molecular , Filogenia
20.
Pharm Biol ; 52(7): 926-32, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24920235

RESUMO

CONTEXT: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown. OBJECTIVE: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro. MATERIALS AND METHODS: To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used. RESULTS: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1ß (4.775 versus 0.713 pg/ml, IC50 = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation. DISCUSSION AND CONCLUSION: Our results indicated that CAPE can modulate mast cell-mediated allergic disease.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ácidos Cafeicos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Álcool Feniletílico/análogos & derivados , Animais , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/efeitos dos fármacos , Histamina/metabolismo , Liberação de Histamina/efeitos dos fármacos , Humanos , Hipersensibilidade/prevenção & controle , Imunoglobulina E/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Mastócitos/citologia , Mastócitos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Álcool Feniletílico/farmacologia , Fosforilação/efeitos dos fármacos
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